Outcomes after ST-elevation myocardial infarction presentation to hospitals with or without a routine primary percutaneous coronary intervention service (ANZACS-QI 46)
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When a patient presents with an ST-elevation myocardial infarction (STEMI), acute reperfusion therapy by either acute percutaneous coronary intervention (primary PCI) or fibrinolysis improves outcomes.1,2 When it can be performed in a timely fashion primary PCI is the preferred approach;3 however, in all other cases current guidelines from the European Society of Cardiology and the American Heart Association advocate that fibrinolysis followed by early PCI is the recommended strategy for STEMI patients with symptom onset less than 12 hours who cannot be transferred to undergo PCI within 120 minutes.3,4 This recommendation is reflected in local guidelines from the New Zealand Branch of the Cardiac Society of Australia and New Zealand (CSANZ)5 and the National Out-of-Hospital STEMI Pathway co-developed by the National Cardiac Network and New Zealand ambulance services.6 The CSANZ guidelines further note that all STEMI patients with successful reperfusion via fibrinolysis should be transferred to a PCI-capable hospital for rescue PCI if appropriate, or invasive coronary angiography ±PCI within 3–24 hours after fibrinolytic therapy.
There are 47 public hospitals that receive STEMI patients in New Zealand, but only nine of these have round-the-clock access to interventional cardiac catheterisation laboratories allowing participation in a routine primary PCI service.7 When acute reperfusion is considered, each of the 38 remaining hospitals and their ambulance service, without local access to primary PCI, must decide whether to pursue a reperfusion strategy of primary PCI (via transfer to a PCI capable hospital without fibrinolysis), or an approach of fibrinolysis by pre-hospital providers or the in-hospital team, followed by a transfer to a PCI-capable hospital for further definitive PCI.8 This is often termed the ‘pharmaco-invasive’ strategy.9,10 These 38 remaining hospitals can be grouped according to their level of service provision into metropolitan hospitals without routine PCI, and rural hospitals. While two of the metropolitan hospitals, Tauranga and Nelson, without routine PCI have a “mixed” service with limited primary PCI availability on certain times and days of the week only, the others have no on-site interventional service. The hospitals without local PCI capability predominantly serve regional or rural communities.11 Rural hospitals specifically differ from the metropolitan hospitals with or without routine access to PCI, in that they are predominately staffed by generalist doctors and nurses without any local specialist support12–14 and have limited access to both basic and advanced diagnostic tests as well as resources such as acute cardiac care unit facilities.15 The potential for both variation in clinical practice and varying thresholds for angiography referral, together with the greater delays to invasive coronary angiography in patients requiring transfer for angiography might adversely affect outcomes following STEMI in these patients.
The aim of this observational cohort study was to assess the outcomes for patients with STEMI according to whether they first present to a metropolitan hospital with a routine all-hours primary PCI service, a metropolitan hospital without routine primary PCI, or to a rural hospital.
Methods
Patient cohorts and data collection
The All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) programme is a clinician-led initiative which aims to advocate for appropriate management of acute coronary syndrome (ACS) patients and to close the gap between evidence-based treatment and daily clinical practice.16 Data sources for the ANZACS-QI programme include the ANZACS-QI registry which collects an in-depth dataset on the limited subset of ACS patients who have a coronary angiogram (approximately 60% of all ACS patients nationwide), and the National administrative datasets which collects limited data for all hospitalisations for ACS and its sub-types recorded using the International Statistical Classification of Diseases and Related Health Problem (ICD10) coding as well as coronary procedure codes. A principle strength of the National datasets are that they collect standardised demographic and clinical data for all New Zealand residents who are admitted to public hospitals.16 To report the burden of non-cardiac comorbidity, we modified the Charlson comorbidity index17 by excluding congestive heart failure. Data from the ANZACS-QI registry has been used to validate the accuracy of the National administrative dataset ACS sub-types (STEMI, NSTEMI, UA) and procedure codes.18 From the National datasets, we identified all confirmed STEMI cases in New Zealand resident patients between 20–79 years of age who presented to a New Zealand public hospital between November 2011–November 2016. Both primary and secondary STEMI diagnostic codes were used. For this analysis we used only the first admission with a STEMI during the time period. This search method was validated against the ANZACS-QI registry to ensure accuracy.18 Post-STEMI mortality, hospitalisation and medication dispensing data were individually linked from mortality and pharmaceutical collections.19 Secondary prevention medications dispensed within three months of hospital discharge are reported. Appendix Table 1 shows the types of data collected in these respective databases.
Patients who present with STEMI can be rapidly transferred between hospitals to undergo appropriate management. We thus applied a previously validated process to “bundle” ACS hospitalisations to ensure a temporally continuous admission under a single index admission episode of care.20 Patients were divided depending on the local STEMI services provided by the hospital that first received the patient.
Patients 80 years and older were excluded. They are a heterogenous group that contribute to a minority of cases (6.1–6.5%), often have comorbidity requiring more individualised treatment decisions, and have disproportionately high rates of mortality (19.8–75%).21–25
Hospital cohorts
Hospitals were divided into three different cohorts with differing STEMI management policies. They were—metropolitan hospitals with routine all-hours access to primary PCI service for STEMI (“routine primary PCI” cohort), metropolitan hospitals that do not provide a routine primary PCI service (“metropolitan without routine PCI” cohort) and mostly provide a pharmaco-invasive strategy (two of these hospitals, Tauranga and Nelson, provide primary PCI at certain times and days of the week) and rural hospitals that also predominately pursue a pharmaco-invasive strategy. These hospital groupings are supported by ANZACS-QI registry data over a similar time period that confirms the dominant management strategies for each cohort (Appendix Table 2). A list of New Zealand hospitals with and without access to routine all-hours primary PCI services are listed in Appendix Table 3.
STEMI management pathways
Patients were managed according to prevailing guidelines.5,6 Patients who presented with STEMI who were clinically eligible for acute reperfusion therapy received either primary PCI or fibrinolysis. Those with a delayed presentation of greater than 12 hours of symptoms, or in whom acute reperfusion was considered clinically inappropriate due to comorbidities received medical therapy only. Those undergoing primary PCI received a loading dose of anti-platelet medications and proceeded to the cardiac catheterisation laboratory for invasive coronary angiography and PCI. Patients undergoing the pharmaco-invasive approach typically received a loading dose of aspirin or another anti-platelet agent and received pharmacological fibrinolysis with bolus intravenous tenecteplase. Patients were then routinely transferred to another hospital with PCI capabilities in order to receive an early invasive coronary angiography and PCI if appropriate. Patients who underwent fibrinolysis which resulted in less than 50% resolution of the elevated ST segment at 60 minutes after fibrinolysis, or recurrence of ST elevation, or ongoing ischemic symptoms, or continuing haemodynamic instability were defined as failed fibrinolysis and were urgently transferred for rescue PCI.
Clinical end points and definitions
Outcomes were available from hospital admission to the end of 2017, to ensure each patient had a minimum possible follow-up of one year. The primary outcome measured was all-cause mortality. The two secondary outcomes were 1) a composite of all major adverse cardiac events (MACE), comprising of a composite of all-cause mortality, myocardial re-infarction, ischaemic or haemorrhagic stroke and new heart failure, and 2) the rate of fatal and non-fatal major bleeding.
Re-infarction, ischaemic stroke, hemorrhagic stroke and heart failure were defined by their respective ICD-10 definitions. Fatal and non-fatal major bleeding were defined by the ICD-10 code for “fatal bleeding”, a primary ICD-10 code for bleeding or a secondary ICD-10 code for bleeding requiring transfusion.
Statistical analysis
Categorical variables were summarised as frequency and percentage. Pearson’s chi-square test was used to compare different types of hospitals. Continuous variables were presented as mean and standard deviation (SD) and/or median with interquartile range (IQR), and the comparisons between types of hospitals were done using nonparametric Mann-Whitney U test as the continuous data was not normally distributed.
Cox proportional hazard regression models were constructed to estimate the hazard ratios and 95% confidence interval for the outcomes after ensuring that the assumption of proportional hazards was met.
All P-values reported were two tailed and a P-value <0.05 was considered significant. Data were analysed using SAS statistical package, version 9.4 (SAS Institute, Cary, NIC). Outcomes were displayed using Kaplan-Meier survival curves using R Studio.
Ethics approval
ANZACS-QI is part of the wider Vascular Informatics Using Epidemiology and the Web (VIEW) study. The VIEW study was approved by the Northern Region Ethics Committee in 2003 (AKY/03/12/314), with subsequent amendments to include the ANZACS-QI registries, and with annual approvals by the National Multi-region Ethics Committee since 2007 (MEC07/19/EXP).
Results
We identified 13,265 records from patients that presented with a STEMI to a New Zealand hospital between 1 November 2011 to 30 November 2016. Of these, 201 records were non-New Zealand residents, 39 had missing socioeconomic data and 2,955 were outside the stated age bracket of 20–79 years old. Five hundred and eighty-two records were for patients identified to have presented with a repeated STEMI episode during the study period. Thus, a total of 9,488 eligible patients participated in the study.
Six thousand one hundred and seventy-nine participants first presented to a metropolitan hospital providing a routine all-hours primary PCI service (routine primary PCI cohort), 2,801 participants first presented to a metropolitan hospital that does not provide a routine primary PCI service (metropolitan without routine PCI cohort) and 508 participants first presented to a rural hospital that does not provide a routine primary PCI service (rural hospital cohort).
Baseline characteristics (Table 1)
Patients presenting to the metropolitan without routine PCI and rural hospital cohort were older, more likely to be female and of Māori ethnicity than patients presenting to a routine primary PCI hospital.
Table 1: Baseline patient characteristics.
The hospitals without access to a routine primary PCI service received a larger proportion of patients who lived in socioeconomically deprived areas. 32.0% of patients in the metropolitan without routine PCI cohort and 28.4% patients in the rural hospital cohort were from the most deprived quintile (NZ Dep13, 9–10) compared to 22.8% of patients in the routine primary PCI cohort. The reciprocal was also true where a larger proportion of patients from the most affluent quintile (NZDep13, 1–2) were initially seen in hospitals of the routine primary PCI cohort.
Prior cardiovascular disease, myocardial infarction, congestive heart failure, PCI and the modified non-cardiac Charlson comorbidity score17 were comparable among the three hospital cohorts. The prevalence of prior CABG was slightly higher within the metropolitan without routine PCI cohort (p=0.045).
Coronary procedures and timing (Table 2)
Eight thousand three hundred and fifty-two (88%) of the 9,488 study participants proceeded for invasive coronary angiography. More patients in the routine primary PCI hospital cohort had angiography during their admission (90.6%) compared to the metropolitan hospital without routine PCI cohort (83.0%), and rural hospital cohort (85.0%) (p<0.001). Of those that proceeded for invasive coronary angiography during the index admission, 91.6% of patients in the routine primary PCI cohort received PCI or CABG surgery during their index admission compared to 80.0% of patients in the metropolitan hospital without routine PCI cohort, and 79.6% in the rural hospital cohort (p<0.001).
Table 2: Angiography, percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) time intervals and rates of medical therapy.
Of those undergoing angiography, more patients presenting to a routine primary PCI hospital (78.9%) received invasive coronary angiography within the first 24 hours of presentation than those to a metropolitan hospital without routine PCI (28.7%), or a rural hospital (25.7%) (p<0.001). Only 13.2% of patients presenting to a routine primary PCI hospital had angiography 24–72 hours after presentation compared to 42.0% of those presenting to a metropolitan without routine PCI hospital, and 46.3% of those to a rural hospital. 7.9% of patients in the routine PCI hospital cohort had invasive coronary angiography beyond 72 hours after presentation compared to 29.3% and 28.0% of the metropolitan without routine PCI, and rural hospital cohorts.
Secondary prevention medications dispensed post-discharge (Table 2)
The dispensing of secondary prevention medications was high across groups but with a slightly lower use of anti-platelet agents and ACEI/ARBs in the non-routine primary PCI groups.
Outcomes (Figures 1,2 and Table 3)
The average follow-up duration for all-cause mortality, was 3.03 years. The all-cause mortality, MACE and major bleeding outcomes are shown using Kaplan Maier survival plots in Figures 1 and 2. The Kaplan-Maier mortality at one and three years was 11.7% and 16.6% for patients presenting to the metropolitan with routine PCI cohort, 12.2% and 16.2% for metropolitan hospitals without routine PCI and 12.6% and 18.7% for rural hospitals.
Figure 1: All-cause mortality.
Figure 2: A) All-cause mortality/non-fatal MI/HF/stroke (MACE); B) fatal/non-fatal bleeding.
The Kaplan-Maier MACE at one and three years was 22.0% and 30.1% for patients presenting to the metropolitan with routine PCI cohort, 24.4% and 31.9% for metropolitan hospitals without routine PCI and 21.5% and 31.0% for rural hospitals.
The Kaplan-Maier major bleeding at one and three years was 6.9% and 8.6% for patients presenting to the metropolitan with routine PCI cohort, 7.5% and 9.1% for metropolitan hospitals without routine PCI and 5.5% and 7.1% for rural hospitals.
After adjusting for age, sex, ethnicity, deprivation score, modified Charlson score and prior CVD, there were no differences in outcomes for patients admitted to each of the three hospital groups (Table 3).
Table 3: Outcomes.
Discussion
This nationwide, real-world study describes the interventional management and outcomes for all hospitalised STEMI patients in New Zealand according to the interventional capability of the hospitals to which they were first admitted. Patients presenting first to a routine primary PCI capable hospital, as opposed to a metropolitan without routine PCI, or a rural hospital, received slightly higher overall rates of coronary angiography and revascularisation and received these more quickly. Of those treated with PCI who presented first to a routine primary PCI capable hospital, nearly four in five received PCI on the day of admission, compared to a quarter of those presenting to other hospitals. Despite the differences in management, all clinical outcomes over a mean of three years follow-up did not differ between patients presenting to each of the three hospital groupings.
Efficacy of reperfusion strategies
This finding is congruent with previous literature examining different STEMI management strategies. Patients who are reperfusion candidates presenting with STEMI to New Zealand hospitals providing all-hours routine primary PCI services proceed for invasive coronary angiography with an aim for performing primary PCI. Reperfusion candidates presenting with STEMI to hospitals without local PCI facilities are transferred to receive primary PCI where possible. However, in most cases a transfer cannot be completed within an appropriate time period (120 minutes) and patients then are administered fibrinolytic therapy as the immediate reperfusion strategy prior to transfer to a hospital with PCI facilities for invasive coronary angiography ± PCI. This strategy is commonly called the pharmaco-invasive approach.9,10
Over the preceding decades, it has been established that primary PCI delivers superior outcomes compared to pharmacological fibrinolysis monotherapy.26 However, despite the delay in accessing PCI inherent within the pharmaco-invasive approach, there is similar efficacy to primary PCI. In a registry study from the Mayo Clinic STEMI network comparing the rates of all-cause mortality between patients undergoing the pharmaco-invasive approach versus primary PCI, showed that the rates of early and late mortality were comparable between the two strategies.27 In a study from the University of Ottawa Heart institute regional STEMI system which employs a policy of primary PCI for patients presenting within a 90km radius of the PCI centre and a pharmaco-invasive strategy for those outside this limit28 displayed the rates of mortality, stroke or reinfarction were no different between the two strategies. The landmark Strategic Reperfusion Early After Myocardial Infarction (STREAM) trial29 assigned STEMI patients to undergo primary PCI versus fibrinolysis with transfer to a PCI capable hospital for a coronary angiography within 6–24 hours. The rate of the 30-day primary endpoint, a composite of death, shock, CHF and reinfarction, was similar among both groups. Other studies have noted similar findings.30–33 Lastly, a meta-analysis consisting of studies up to 201734 have concluded there is no difference in short-term and long-term mortality between the two reperfusion strategies as long as symptom onset to device time in primary PCI did not exceed 200 minutes.
Timing of angiography
A prominent finding in our results is the delay in proceeding for angiography for patients presenting to rural and metropolitan hospitals with no routine PCI available. 28.7% of metropolitan hospitals without PCI, and 25.7% of the rural hospital cohort were able to access invasive angiography within 24 hours. This contrasts with 78.9% of patients who presented to hospitals providing routine primary PCI proceeding to invasive angiography within 24 hours.
The New Zealand Cardiac Clinical Network and the Ministry of Health recommend a “three-day door-to-catheter target” for all acute coronary syndrome (including unstable angina, NSTEMI and STEMI) admissions.35 The Cardiac Society of Australia and New Zealand recommends all STEMI patients with successful reperfusion via fibrinolysis should be transferred to a PCI capable hospital for cardiac catherisation within 24 hours after fibrinolytic therapy.5 While our study was unable to determine when the transfer to a PCI centre took place, it showed that only one-quarter of patients who present to a rural or metropolitan hospital with no routine primary PCI had angiography within this 24-hour window. This finding is similar to a nationwide audit in 2012 that showed 22% of patients presenting with STEMI to non-interventional hospitals received routine angiography within 24 hours.20 Nearly one-third of patients who present to a rural or metropolitan hospital with no routine primary PCI were awaiting cardiac catheterisation more than 72 hours post-STEMI.
Delays in in receiving angiography primarily reflect shortfalls in processes to ensure early transfer of patients to an interventional hospital together with appropriate prioritisation on arrival. This has previously been noted in a New Zealand study which reported that patients are more likely to wait longer for cardiac catherisation in districts without interventional facilities after ACS.35 New Zealand has a small and geographically dispersed population with smaller regional and rural centres. These hospitals do not have the concentration of healthcare resources and specialist care as seen in hospitals with a routine primary PCI service. Instead, metropolitan hospitals without routine primary PCI and rural hospitals are more likely to be served by general physicians in metropolitan hospitals or generalist rural hospital doctors in rural hospitals13 leading to a range of inter-physician differences in the threshold for referrals, delays in transfer and proceeding for cardiac catherisation. Reduced rates of investigations (eg, ETT, CT scans) for geographically isolated areas has been demonstrated previously in New Zealand.36,37 The optimal management of STEMI involves prompt inter-disciplinary and inter-regional co-operation and co-ordination among frontline ambulance staff, helicopter crews, STEMI co-ordinators, rural nurses, general practitioners, general and emergency physicians, cardiac catherisation laboratory staff and interventional cardiologists. Any misaligned communication or expectations within this chain of care results in prolonged times from first medical contact to crossing of the coronary occlusion or stenosis with a wire. It has been recognised that it is essential to implement standardised pathways for management to reduce uncertainty and inequality nationwide. This has resulted in the New Zealand out-of-hospital STEMI pathway in 2016.6
Differences in rates of angiography and revascularisation
There were lower rates of invasive coronary angiography in patients presenting to hospitals without routine primary PCI services. Patients in these cohorts were slightly less likely to receive invasive coronary angiography during their admission, with 83–85% proceeding for cardiac catheterisation compared to 90.6% of patients presenting to hospitals providing a routine all-hours primary PCI service. This may be contributed by the different baseline characteristics of the three cohorts, in particular the older age of the non-routine PCI hospital cohorts. Among patients who did have a diagnostic angiogram, the gap for revascularisation was even greater; 91.6% of these patients in the routine primary PCI group received revascularisation by either PCI or CABG during their index admission compared to 80.0% of patients in the metropolitan hospitals without routine PCI cohort and 79.6% in the rural hospital groups. This is likely in part due to a higher rate of non-obstructive coronary artery disease in those already treated with fibrinolytic therapy, which may have lysed the thrombus who therefore do not need revascularisation.38
Rural-urban differences
Although we have primarily created hospital cohorts based on STEMI management capabilities, these groups also represent a rural-urban divide. Hospitals providing routine primary PCI are located within the largest metropolitan centres, whereas hospitals of the non-routine PCI cohorts are in regional urban areas and rural communities. We previously reported that ≥80% of patients with STEMI who lived in predominantly rural district health boards (DHBs) received pharmaco-invasive therapy.39 Patients who presented to metropolitan hospitals without routine PCI and rural hospitals were more likely to be older, female, from a more deprived socioeconomic quintile and of Māori or European ethnicity. After adjustment, there were no significant differences in outcomes between patients initially presenting to a rural compared with a routine primary PCI hospital. This is congruent with previous Australian40 and Chinese studies41 which found that there was no difference in mortality post STEMI between metropolitan and rural regions. This study shows that great progress has been made in New Zealand over the last two decades with a closing of the gap, especially for mortality, in outcomes and access to intervention between hospitals with PCI and those without.42 It is a concern that patients presenting to non-primary PCI hospitals tended to have greater levels of socioeconomic deprivation. Delays in angiography associated with location of care and socioeconomic status have been demonstrated previously in a study in the US.43 Most other studies have examined the broader topic of acute coronary syndrome, with varied findings. In Canada, patients who presented with ACS from non-metropolitan areas were less likely to receive cardiac catheterisation within one day and those from the lowest income area within non-metropolitan areas were less likely to have a coronary angiogram within seven days compared to their more affluent counterparts living in metropolitan areas.44 Also, women from poor-income neighbourhoods were associated with a poorer odds of having coronary angiography and a higher mortality within 30 days.45 In contrast, a study in Australia found that socioeconomic status was not related to differences in having coronary angiography after ACS.46
Safety outcomes
There was no statistically significant difference in major bleeding between the three cohorts. There was a small, but significant, increase in haemorrhagic stroke within the metropolitan without routine PCI cohort (Table 2). The literature is varied when examining the safety aspects of the pharmaco-invasive strategy. Two studies28,29 demonstrated increased rates of haemorrhagic stroke with the pharmaco-invasive method. This increased safety risk was found to be confined to patients greater than 75 years of age in a sub-analysis of one study.29 This has led to the recommendation to use lower dose bolus fibrinolytic therapy in patients greater than 75 years of age.
Limitations
We compared practice and outcomes according to which three types of hospital a patient initially presented to. Hospitals were categorised according to their levels of availability of primary PCI services and access to specialist services. Although each hospital has defined reperfusion policies, STEMI management is not necessarily consistent for each hospital within these three groups. ANZACS-QI data shows that 10.5–14% of patients who present to hospitals that do not provide a routine primary PCI service do indeed proceed for primary PCI (Appendix Table 2). The most prominent example of this are a subset of hospitals such as Tauranga or Nelson Hospital who offer primary PCI within limited hours or within the limits of staffing availability. In some regions a small number of patients are flown directly to a PCI capable centre for primary PCI and so may bypass their local hospital. In addition to the effect of acute reperfusion therapy, outcomes are also likely to be dependent on the other components of the STEMI pathway management including pharmacological management, pre-hospital vs in-hospital fibrinolysis and the availability of appropriate and timely transfer to tertiary centres. These may also vary between hospitals within our three service groups. Furthermore, the national datasets used in this study do not reliably record whether patients were treated with acute reperfusion as primary PCI and fibrinolysis are not coded. Primary PCI cases and those receiving fibrinolysis and subsequent angiography can be identified using the separate ANZACS-QI registry16,38 but there is no data source which reliably identifies patients treated with fibrinolysis who do not proceed to an angiogram. A consequence of this is that for hospitals without routine primary PCI availability we cannot reliably report the proportion of STEMI patients who do not receive acute reperfusion therapy. We were also unable to capture any patient who died without reaching a hospital or who died after STEMI discharge outside of New Zealand.
Conclusion
Our study has demonstrated that patients who present with STEMI to hospitals without a routine primary PCI service are less likely to receive coronary angiography, wait longer for angiography and are less likely to receive coronary revascularisation. This is likely due to the geographical isolation of these hospitals from PCI facilities that results in the differences in STEMI management, however there may be other factors that influence the timing of angiography and primary PCI. Despite differences in management, we did not find any differences in mortality, MACE or major bleeding rates following STEMI between the three different cohorts of hospitals. This is a tribute to the current systems of STEMI care including timely pharmacological reperfusion, appropriate bypass of selected non-interventional hospitals with transfer of patients to interventional centres and use of secondary prevention medication.
This study adds to the growing body of international evidence that the pharmaco-invasive approach is a viable method in STEMI patients who present to hospitals without PCI capabilities. In the New Zealand context, this may mean future resources could be efficiently used in further optimising existing STEMI networks.
Appendix
Appendix Table 1: Outline of data collected for the ANZACS-QI national Routine Information cohort.16
Appendix Table 2: Proportion of STEMI reperfusion strategies between hospital groupings. Data collected from the ANZACS-QI registry between 1 September 2013–30 November 2016.
Appendix Table 3: List of New Zealand public hospitals that receive STEMI patients, with and without access to cardiac catherisation services.
Summary
Abstract
Aim
Primary percutaneous coronary intervention (PCI) is the optimal reperfusion strategy to manage ST-elevation myocardial infarction (STEMI). Where timely primary PCI cannot be achieved, an initial pharmacological reperfusion strategy is recommended with subsequent transfer to a PCI-capable hospital. The study aim was to assess STEMI outcomes according to the interventional capability of the New Zealand hospital to which patients initially present.
Method
Nine thousand four hundred and eighty-eight New Zealand patients, aged 20–79 years, admitted with STEMI to a public hospital were identified. Patients were categorised into three groups—metropolitan hospitals with all-hours access to primary PCI (routine primary PCI cohort), metropolitan hospitals without routine access to PCI, and rural hospitals. The primary outcome was all-cause mortality. Secondary outcomes were major adverse cardiac events (MACE) and major bleeding.
Results
Invasive coronary angiography was more frequent in the routine primary PCI cohort compared to metropolitan hospitals without routine access to PCI and rural hospitals (90.6 vs 83.0 vs 85.0% respectively; p<0.001) and occurred more commonly on the day of admission (78.9 vs 28.7 vs 25.7% respectively; p<0.001). There were no differences in multivariable adjusted all-cause mortality, MACE or major bleeding between patients admitted to any of the hospital groupings.
Conclusion
Outcomes after STEMI in New Zealand are similar regardless of the interventional capability of the hospital where they first present.
Author Information
Acknowledgements
Correspondence
Correspondence Email
Competing Interests
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33. Danchin N, Puymirat E, Steg PG, et al. Five-year survival in patients with ST-segment-elevation myocardial infarction according to modalities of reperfusion therapy: the French Registry on Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) 2005 Cohort. Circulation. 2014; 129:1629–36.
34. Siddiqi TJ, Usman MS, Khan MS, et al. Meta-Analysis Comparing Primary Percutaneous Coronary Intervention Versus Pharmacoinvasive Therapy in Transfer Patients with ST-Elevation Myocardial Infarction. Am J Cardiol. 2018; 122:542–547.
35. Williams MJ, Harding SA, Devlin G, et al. National variation in coronary angiography rates and timing after an acute coronary syndrome in New Zealand (ANZACS-QI 6). N Z Med J. 2016; 129:66–78.
36. Nixon G, Samaranayaka A, de Graaf B, et al. The impact of a rural scanner in overcoming urban versus rural disparities in the utilisation of computed tomography. Aust J Rural Health. 2015; 23:150–4.
37. Blattner K, Nixon G, Horgan C, et al. Evaluation of a rural primary-referred cardiac exercise tolerance test service. N Z Med J. 2014; 127:63–70.
38. Kerr A, Lee M, Grey C, et al. Acute reperfusion for ST-elevation myocardial infarction in New Zealand (2015-2017): patient and system delay (ANZACS-QI 29). N Z Med J. 2019; 132:41–59.
39. Kerr A. Fibrinolysis for STEMI in New Zealand Public Hospitals July 2015-June 2017 - an ANZACS-QI Registry Report. [In Press].
40. Huynh LT, Rankin JM, Tideman P, et al. Reperfusion therapy in the acute management of ST-segment-elevation myocardial infarction in Australia: findings from the ACACIA registry. Med J Aust. 2010; 193(9):496–501.
41. Li X, Murugiah K, Li J, et al. Urban-Rural Comparisons in Hospital Admission, Treatments, and Outcomes for ST-Segment-Elevation Myocardial Infarction in China From 2001 to 2011: A Retrospective Analysis From the China PEACE Study (Patient-Centered Evaluative Assessment of Cardiac Events). Circ Cardiovasc Qual Outcomes. 2017; 10.
42. Tang EW, Wong CK, Herbison P. Community hospital versus tertiary hospital comparison in the treatment and outcome of patients with acute coronary syndrome: a New Zealand experience. N Z Med J. 2006; 119:U2078.
43. Yong CM, Abnousi F, Asch SM, Heidenreich PA. Socioeconomic inequalities in quality of care and outcomes among patients with acute coronary syndrome in the modern era of drug eluting stents. J Am Heart Assoc. 2014; 3:e001029.
44. Fabreau GE, Leung AA, Southern DA, et al. Area Median Income and Metropolitan Versus Nonmetropolitan Location of Care for Acute Coronary Syndromes: A Complex Interaction of Social Determinants. J Am Heart Assoc. 2016; 5.
45. Fabreau GE, Leung AA, Southern DA, et al. Sex, socioeconomic status, access to cardiac catheterization, and outcomes for acute coronary syndromes in the context of universal healthcare coverage. Circ Cardiovasc Qual Outcomes. 2014; 7:540–9.
46. Hyun K, Redfern J, Woodward M, et al. Socioeconomic Equity in the Receipt of In-Hospital Care and Outcomes in Australian Acute Coronary Syndrome Patients: The CONCORDANCE Registry. Heart Lung Circ. 2018; 27:1398–1405.
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Outcomes after ST-elevation myocardial infarction presentation to hospitals with or without a routine primary percutaneous coronary intervention service (ANZACS-QI 46)
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When a patient presents with an ST-elevation myocardial infarction (STEMI), acute reperfusion therapy by either acute percutaneous coronary intervention (primary PCI) or fibrinolysis improves outcomes.1,2 When it can be performed in a timely fashion primary PCI is the preferred approach;3 however, in all other cases current guidelines from the European Society of Cardiology and the American Heart Association advocate that fibrinolysis followed by early PCI is the recommended strategy for STEMI patients with symptom onset less than 12 hours who cannot be transferred to undergo PCI within 120 minutes.3,4 This recommendation is reflected in local guidelines from the New Zealand Branch of the Cardiac Society of Australia and New Zealand (CSANZ)5 and the National Out-of-Hospital STEMI Pathway co-developed by the National Cardiac Network and New Zealand ambulance services.6 The CSANZ guidelines further note that all STEMI patients with successful reperfusion via fibrinolysis should be transferred to a PCI-capable hospital for rescue PCI if appropriate, or invasive coronary angiography ±PCI within 3–24 hours after fibrinolytic therapy.
There are 47 public hospitals that receive STEMI patients in New Zealand, but only nine of these have round-the-clock access to interventional cardiac catheterisation laboratories allowing participation in a routine primary PCI service.7 When acute reperfusion is considered, each of the 38 remaining hospitals and their ambulance service, without local access to primary PCI, must decide whether to pursue a reperfusion strategy of primary PCI (via transfer to a PCI capable hospital without fibrinolysis), or an approach of fibrinolysis by pre-hospital providers or the in-hospital team, followed by a transfer to a PCI-capable hospital for further definitive PCI.8 This is often termed the ‘pharmaco-invasive’ strategy.9,10 These 38 remaining hospitals can be grouped according to their level of service provision into metropolitan hospitals without routine PCI, and rural hospitals. While two of the metropolitan hospitals, Tauranga and Nelson, without routine PCI have a “mixed” service with limited primary PCI availability on certain times and days of the week only, the others have no on-site interventional service. The hospitals without local PCI capability predominantly serve regional or rural communities.11 Rural hospitals specifically differ from the metropolitan hospitals with or without routine access to PCI, in that they are predominately staffed by generalist doctors and nurses without any local specialist support12–14 and have limited access to both basic and advanced diagnostic tests as well as resources such as acute cardiac care unit facilities.15 The potential for both variation in clinical practice and varying thresholds for angiography referral, together with the greater delays to invasive coronary angiography in patients requiring transfer for angiography might adversely affect outcomes following STEMI in these patients.
The aim of this observational cohort study was to assess the outcomes for patients with STEMI according to whether they first present to a metropolitan hospital with a routine all-hours primary PCI service, a metropolitan hospital without routine primary PCI, or to a rural hospital.
Methods
Patient cohorts and data collection
The All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) programme is a clinician-led initiative which aims to advocate for appropriate management of acute coronary syndrome (ACS) patients and to close the gap between evidence-based treatment and daily clinical practice.16 Data sources for the ANZACS-QI programme include the ANZACS-QI registry which collects an in-depth dataset on the limited subset of ACS patients who have a coronary angiogram (approximately 60% of all ACS patients nationwide), and the National administrative datasets which collects limited data for all hospitalisations for ACS and its sub-types recorded using the International Statistical Classification of Diseases and Related Health Problem (ICD10) coding as well as coronary procedure codes. A principle strength of the National datasets are that they collect standardised demographic and clinical data for all New Zealand residents who are admitted to public hospitals.16 To report the burden of non-cardiac comorbidity, we modified the Charlson comorbidity index17 by excluding congestive heart failure. Data from the ANZACS-QI registry has been used to validate the accuracy of the National administrative dataset ACS sub-types (STEMI, NSTEMI, UA) and procedure codes.18 From the National datasets, we identified all confirmed STEMI cases in New Zealand resident patients between 20–79 years of age who presented to a New Zealand public hospital between November 2011–November 2016. Both primary and secondary STEMI diagnostic codes were used. For this analysis we used only the first admission with a STEMI during the time period. This search method was validated against the ANZACS-QI registry to ensure accuracy.18 Post-STEMI mortality, hospitalisation and medication dispensing data were individually linked from mortality and pharmaceutical collections.19 Secondary prevention medications dispensed within three months of hospital discharge are reported. Appendix Table 1 shows the types of data collected in these respective databases.
Patients who present with STEMI can be rapidly transferred between hospitals to undergo appropriate management. We thus applied a previously validated process to “bundle” ACS hospitalisations to ensure a temporally continuous admission under a single index admission episode of care.20 Patients were divided depending on the local STEMI services provided by the hospital that first received the patient.
Patients 80 years and older were excluded. They are a heterogenous group that contribute to a minority of cases (6.1–6.5%), often have comorbidity requiring more individualised treatment decisions, and have disproportionately high rates of mortality (19.8–75%).21–25
Hospital cohorts
Hospitals were divided into three different cohorts with differing STEMI management policies. They were—metropolitan hospitals with routine all-hours access to primary PCI service for STEMI (“routine primary PCI” cohort), metropolitan hospitals that do not provide a routine primary PCI service (“metropolitan without routine PCI” cohort) and mostly provide a pharmaco-invasive strategy (two of these hospitals, Tauranga and Nelson, provide primary PCI at certain times and days of the week) and rural hospitals that also predominately pursue a pharmaco-invasive strategy. These hospital groupings are supported by ANZACS-QI registry data over a similar time period that confirms the dominant management strategies for each cohort (Appendix Table 2). A list of New Zealand hospitals with and without access to routine all-hours primary PCI services are listed in Appendix Table 3.
STEMI management pathways
Patients were managed according to prevailing guidelines.5,6 Patients who presented with STEMI who were clinically eligible for acute reperfusion therapy received either primary PCI or fibrinolysis. Those with a delayed presentation of greater than 12 hours of symptoms, or in whom acute reperfusion was considered clinically inappropriate due to comorbidities received medical therapy only. Those undergoing primary PCI received a loading dose of anti-platelet medications and proceeded to the cardiac catheterisation laboratory for invasive coronary angiography and PCI. Patients undergoing the pharmaco-invasive approach typically received a loading dose of aspirin or another anti-platelet agent and received pharmacological fibrinolysis with bolus intravenous tenecteplase. Patients were then routinely transferred to another hospital with PCI capabilities in order to receive an early invasive coronary angiography and PCI if appropriate. Patients who underwent fibrinolysis which resulted in less than 50% resolution of the elevated ST segment at 60 minutes after fibrinolysis, or recurrence of ST elevation, or ongoing ischemic symptoms, or continuing haemodynamic instability were defined as failed fibrinolysis and were urgently transferred for rescue PCI.
Clinical end points and definitions
Outcomes were available from hospital admission to the end of 2017, to ensure each patient had a minimum possible follow-up of one year. The primary outcome measured was all-cause mortality. The two secondary outcomes were 1) a composite of all major adverse cardiac events (MACE), comprising of a composite of all-cause mortality, myocardial re-infarction, ischaemic or haemorrhagic stroke and new heart failure, and 2) the rate of fatal and non-fatal major bleeding.
Re-infarction, ischaemic stroke, hemorrhagic stroke and heart failure were defined by their respective ICD-10 definitions. Fatal and non-fatal major bleeding were defined by the ICD-10 code for “fatal bleeding”, a primary ICD-10 code for bleeding or a secondary ICD-10 code for bleeding requiring transfusion.
Statistical analysis
Categorical variables were summarised as frequency and percentage. Pearson’s chi-square test was used to compare different types of hospitals. Continuous variables were presented as mean and standard deviation (SD) and/or median with interquartile range (IQR), and the comparisons between types of hospitals were done using nonparametric Mann-Whitney U test as the continuous data was not normally distributed.
Cox proportional hazard regression models were constructed to estimate the hazard ratios and 95% confidence interval for the outcomes after ensuring that the assumption of proportional hazards was met.
All P-values reported were two tailed and a P-value <0.05 was considered significant. Data were analysed using SAS statistical package, version 9.4 (SAS Institute, Cary, NIC). Outcomes were displayed using Kaplan-Meier survival curves using R Studio.
Ethics approval
ANZACS-QI is part of the wider Vascular Informatics Using Epidemiology and the Web (VIEW) study. The VIEW study was approved by the Northern Region Ethics Committee in 2003 (AKY/03/12/314), with subsequent amendments to include the ANZACS-QI registries, and with annual approvals by the National Multi-region Ethics Committee since 2007 (MEC07/19/EXP).
Results
We identified 13,265 records from patients that presented with a STEMI to a New Zealand hospital between 1 November 2011 to 30 November 2016. Of these, 201 records were non-New Zealand residents, 39 had missing socioeconomic data and 2,955 were outside the stated age bracket of 20–79 years old. Five hundred and eighty-two records were for patients identified to have presented with a repeated STEMI episode during the study period. Thus, a total of 9,488 eligible patients participated in the study.
Six thousand one hundred and seventy-nine participants first presented to a metropolitan hospital providing a routine all-hours primary PCI service (routine primary PCI cohort), 2,801 participants first presented to a metropolitan hospital that does not provide a routine primary PCI service (metropolitan without routine PCI cohort) and 508 participants first presented to a rural hospital that does not provide a routine primary PCI service (rural hospital cohort).
Baseline characteristics (Table 1)
Patients presenting to the metropolitan without routine PCI and rural hospital cohort were older, more likely to be female and of Māori ethnicity than patients presenting to a routine primary PCI hospital.
Table 1: Baseline patient characteristics.
The hospitals without access to a routine primary PCI service received a larger proportion of patients who lived in socioeconomically deprived areas. 32.0% of patients in the metropolitan without routine PCI cohort and 28.4% patients in the rural hospital cohort were from the most deprived quintile (NZ Dep13, 9–10) compared to 22.8% of patients in the routine primary PCI cohort. The reciprocal was also true where a larger proportion of patients from the most affluent quintile (NZDep13, 1–2) were initially seen in hospitals of the routine primary PCI cohort.
Prior cardiovascular disease, myocardial infarction, congestive heart failure, PCI and the modified non-cardiac Charlson comorbidity score17 were comparable among the three hospital cohorts. The prevalence of prior CABG was slightly higher within the metropolitan without routine PCI cohort (p=0.045).
Coronary procedures and timing (Table 2)
Eight thousand three hundred and fifty-two (88%) of the 9,488 study participants proceeded for invasive coronary angiography. More patients in the routine primary PCI hospital cohort had angiography during their admission (90.6%) compared to the metropolitan hospital without routine PCI cohort (83.0%), and rural hospital cohort (85.0%) (p<0.001). Of those that proceeded for invasive coronary angiography during the index admission, 91.6% of patients in the routine primary PCI cohort received PCI or CABG surgery during their index admission compared to 80.0% of patients in the metropolitan hospital without routine PCI cohort, and 79.6% in the rural hospital cohort (p<0.001).
Table 2: Angiography, percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) time intervals and rates of medical therapy.
Of those undergoing angiography, more patients presenting to a routine primary PCI hospital (78.9%) received invasive coronary angiography within the first 24 hours of presentation than those to a metropolitan hospital without routine PCI (28.7%), or a rural hospital (25.7%) (p<0.001). Only 13.2% of patients presenting to a routine primary PCI hospital had angiography 24–72 hours after presentation compared to 42.0% of those presenting to a metropolitan without routine PCI hospital, and 46.3% of those to a rural hospital. 7.9% of patients in the routine PCI hospital cohort had invasive coronary angiography beyond 72 hours after presentation compared to 29.3% and 28.0% of the metropolitan without routine PCI, and rural hospital cohorts.
Secondary prevention medications dispensed post-discharge (Table 2)
The dispensing of secondary prevention medications was high across groups but with a slightly lower use of anti-platelet agents and ACEI/ARBs in the non-routine primary PCI groups.
Outcomes (Figures 1,2 and Table 3)
The average follow-up duration for all-cause mortality, was 3.03 years. The all-cause mortality, MACE and major bleeding outcomes are shown using Kaplan Maier survival plots in Figures 1 and 2. The Kaplan-Maier mortality at one and three years was 11.7% and 16.6% for patients presenting to the metropolitan with routine PCI cohort, 12.2% and 16.2% for metropolitan hospitals without routine PCI and 12.6% and 18.7% for rural hospitals.
Figure 1: All-cause mortality.
Figure 2: A) All-cause mortality/non-fatal MI/HF/stroke (MACE); B) fatal/non-fatal bleeding.
The Kaplan-Maier MACE at one and three years was 22.0% and 30.1% for patients presenting to the metropolitan with routine PCI cohort, 24.4% and 31.9% for metropolitan hospitals without routine PCI and 21.5% and 31.0% for rural hospitals.
The Kaplan-Maier major bleeding at one and three years was 6.9% and 8.6% for patients presenting to the metropolitan with routine PCI cohort, 7.5% and 9.1% for metropolitan hospitals without routine PCI and 5.5% and 7.1% for rural hospitals.
After adjusting for age, sex, ethnicity, deprivation score, modified Charlson score and prior CVD, there were no differences in outcomes for patients admitted to each of the three hospital groups (Table 3).
Table 3: Outcomes.
Discussion
This nationwide, real-world study describes the interventional management and outcomes for all hospitalised STEMI patients in New Zealand according to the interventional capability of the hospitals to which they were first admitted. Patients presenting first to a routine primary PCI capable hospital, as opposed to a metropolitan without routine PCI, or a rural hospital, received slightly higher overall rates of coronary angiography and revascularisation and received these more quickly. Of those treated with PCI who presented first to a routine primary PCI capable hospital, nearly four in five received PCI on the day of admission, compared to a quarter of those presenting to other hospitals. Despite the differences in management, all clinical outcomes over a mean of three years follow-up did not differ between patients presenting to each of the three hospital groupings.
Efficacy of reperfusion strategies
This finding is congruent with previous literature examining different STEMI management strategies. Patients who are reperfusion candidates presenting with STEMI to New Zealand hospitals providing all-hours routine primary PCI services proceed for invasive coronary angiography with an aim for performing primary PCI. Reperfusion candidates presenting with STEMI to hospitals without local PCI facilities are transferred to receive primary PCI where possible. However, in most cases a transfer cannot be completed within an appropriate time period (120 minutes) and patients then are administered fibrinolytic therapy as the immediate reperfusion strategy prior to transfer to a hospital with PCI facilities for invasive coronary angiography ± PCI. This strategy is commonly called the pharmaco-invasive approach.9,10
Over the preceding decades, it has been established that primary PCI delivers superior outcomes compared to pharmacological fibrinolysis monotherapy.26 However, despite the delay in accessing PCI inherent within the pharmaco-invasive approach, there is similar efficacy to primary PCI. In a registry study from the Mayo Clinic STEMI network comparing the rates of all-cause mortality between patients undergoing the pharmaco-invasive approach versus primary PCI, showed that the rates of early and late mortality were comparable between the two strategies.27 In a study from the University of Ottawa Heart institute regional STEMI system which employs a policy of primary PCI for patients presenting within a 90km radius of the PCI centre and a pharmaco-invasive strategy for those outside this limit28 displayed the rates of mortality, stroke or reinfarction were no different between the two strategies. The landmark Strategic Reperfusion Early After Myocardial Infarction (STREAM) trial29 assigned STEMI patients to undergo primary PCI versus fibrinolysis with transfer to a PCI capable hospital for a coronary angiography within 6–24 hours. The rate of the 30-day primary endpoint, a composite of death, shock, CHF and reinfarction, was similar among both groups. Other studies have noted similar findings.30–33 Lastly, a meta-analysis consisting of studies up to 201734 have concluded there is no difference in short-term and long-term mortality between the two reperfusion strategies as long as symptom onset to device time in primary PCI did not exceed 200 minutes.
Timing of angiography
A prominent finding in our results is the delay in proceeding for angiography for patients presenting to rural and metropolitan hospitals with no routine PCI available. 28.7% of metropolitan hospitals without PCI, and 25.7% of the rural hospital cohort were able to access invasive angiography within 24 hours. This contrasts with 78.9% of patients who presented to hospitals providing routine primary PCI proceeding to invasive angiography within 24 hours.
The New Zealand Cardiac Clinical Network and the Ministry of Health recommend a “three-day door-to-catheter target” for all acute coronary syndrome (including unstable angina, NSTEMI and STEMI) admissions.35 The Cardiac Society of Australia and New Zealand recommends all STEMI patients with successful reperfusion via fibrinolysis should be transferred to a PCI capable hospital for cardiac catherisation within 24 hours after fibrinolytic therapy.5 While our study was unable to determine when the transfer to a PCI centre took place, it showed that only one-quarter of patients who present to a rural or metropolitan hospital with no routine primary PCI had angiography within this 24-hour window. This finding is similar to a nationwide audit in 2012 that showed 22% of patients presenting with STEMI to non-interventional hospitals received routine angiography within 24 hours.20 Nearly one-third of patients who present to a rural or metropolitan hospital with no routine primary PCI were awaiting cardiac catheterisation more than 72 hours post-STEMI.
Delays in in receiving angiography primarily reflect shortfalls in processes to ensure early transfer of patients to an interventional hospital together with appropriate prioritisation on arrival. This has previously been noted in a New Zealand study which reported that patients are more likely to wait longer for cardiac catherisation in districts without interventional facilities after ACS.35 New Zealand has a small and geographically dispersed population with smaller regional and rural centres. These hospitals do not have the concentration of healthcare resources and specialist care as seen in hospitals with a routine primary PCI service. Instead, metropolitan hospitals without routine primary PCI and rural hospitals are more likely to be served by general physicians in metropolitan hospitals or generalist rural hospital doctors in rural hospitals13 leading to a range of inter-physician differences in the threshold for referrals, delays in transfer and proceeding for cardiac catherisation. Reduced rates of investigations (eg, ETT, CT scans) for geographically isolated areas has been demonstrated previously in New Zealand.36,37 The optimal management of STEMI involves prompt inter-disciplinary and inter-regional co-operation and co-ordination among frontline ambulance staff, helicopter crews, STEMI co-ordinators, rural nurses, general practitioners, general and emergency physicians, cardiac catherisation laboratory staff and interventional cardiologists. Any misaligned communication or expectations within this chain of care results in prolonged times from first medical contact to crossing of the coronary occlusion or stenosis with a wire. It has been recognised that it is essential to implement standardised pathways for management to reduce uncertainty and inequality nationwide. This has resulted in the New Zealand out-of-hospital STEMI pathway in 2016.6
Differences in rates of angiography and revascularisation
There were lower rates of invasive coronary angiography in patients presenting to hospitals without routine primary PCI services. Patients in these cohorts were slightly less likely to receive invasive coronary angiography during their admission, with 83–85% proceeding for cardiac catheterisation compared to 90.6% of patients presenting to hospitals providing a routine all-hours primary PCI service. This may be contributed by the different baseline characteristics of the three cohorts, in particular the older age of the non-routine PCI hospital cohorts. Among patients who did have a diagnostic angiogram, the gap for revascularisation was even greater; 91.6% of these patients in the routine primary PCI group received revascularisation by either PCI or CABG during their index admission compared to 80.0% of patients in the metropolitan hospitals without routine PCI cohort and 79.6% in the rural hospital groups. This is likely in part due to a higher rate of non-obstructive coronary artery disease in those already treated with fibrinolytic therapy, which may have lysed the thrombus who therefore do not need revascularisation.38
Rural-urban differences
Although we have primarily created hospital cohorts based on STEMI management capabilities, these groups also represent a rural-urban divide. Hospitals providing routine primary PCI are located within the largest metropolitan centres, whereas hospitals of the non-routine PCI cohorts are in regional urban areas and rural communities. We previously reported that ≥80% of patients with STEMI who lived in predominantly rural district health boards (DHBs) received pharmaco-invasive therapy.39 Patients who presented to metropolitan hospitals without routine PCI and rural hospitals were more likely to be older, female, from a more deprived socioeconomic quintile and of Māori or European ethnicity. After adjustment, there were no significant differences in outcomes between patients initially presenting to a rural compared with a routine primary PCI hospital. This is congruent with previous Australian40 and Chinese studies41 which found that there was no difference in mortality post STEMI between metropolitan and rural regions. This study shows that great progress has been made in New Zealand over the last two decades with a closing of the gap, especially for mortality, in outcomes and access to intervention between hospitals with PCI and those without.42 It is a concern that patients presenting to non-primary PCI hospitals tended to have greater levels of socioeconomic deprivation. Delays in angiography associated with location of care and socioeconomic status have been demonstrated previously in a study in the US.43 Most other studies have examined the broader topic of acute coronary syndrome, with varied findings. In Canada, patients who presented with ACS from non-metropolitan areas were less likely to receive cardiac catheterisation within one day and those from the lowest income area within non-metropolitan areas were less likely to have a coronary angiogram within seven days compared to their more affluent counterparts living in metropolitan areas.44 Also, women from poor-income neighbourhoods were associated with a poorer odds of having coronary angiography and a higher mortality within 30 days.45 In contrast, a study in Australia found that socioeconomic status was not related to differences in having coronary angiography after ACS.46
Safety outcomes
There was no statistically significant difference in major bleeding between the three cohorts. There was a small, but significant, increase in haemorrhagic stroke within the metropolitan without routine PCI cohort (Table 2). The literature is varied when examining the safety aspects of the pharmaco-invasive strategy. Two studies28,29 demonstrated increased rates of haemorrhagic stroke with the pharmaco-invasive method. This increased safety risk was found to be confined to patients greater than 75 years of age in a sub-analysis of one study.29 This has led to the recommendation to use lower dose bolus fibrinolytic therapy in patients greater than 75 years of age.
Limitations
We compared practice and outcomes according to which three types of hospital a patient initially presented to. Hospitals were categorised according to their levels of availability of primary PCI services and access to specialist services. Although each hospital has defined reperfusion policies, STEMI management is not necessarily consistent for each hospital within these three groups. ANZACS-QI data shows that 10.5–14% of patients who present to hospitals that do not provide a routine primary PCI service do indeed proceed for primary PCI (Appendix Table 2). The most prominent example of this are a subset of hospitals such as Tauranga or Nelson Hospital who offer primary PCI within limited hours or within the limits of staffing availability. In some regions a small number of patients are flown directly to a PCI capable centre for primary PCI and so may bypass their local hospital. In addition to the effect of acute reperfusion therapy, outcomes are also likely to be dependent on the other components of the STEMI pathway management including pharmacological management, pre-hospital vs in-hospital fibrinolysis and the availability of appropriate and timely transfer to tertiary centres. These may also vary between hospitals within our three service groups. Furthermore, the national datasets used in this study do not reliably record whether patients were treated with acute reperfusion as primary PCI and fibrinolysis are not coded. Primary PCI cases and those receiving fibrinolysis and subsequent angiography can be identified using the separate ANZACS-QI registry16,38 but there is no data source which reliably identifies patients treated with fibrinolysis who do not proceed to an angiogram. A consequence of this is that for hospitals without routine primary PCI availability we cannot reliably report the proportion of STEMI patients who do not receive acute reperfusion therapy. We were also unable to capture any patient who died without reaching a hospital or who died after STEMI discharge outside of New Zealand.
Conclusion
Our study has demonstrated that patients who present with STEMI to hospitals without a routine primary PCI service are less likely to receive coronary angiography, wait longer for angiography and are less likely to receive coronary revascularisation. This is likely due to the geographical isolation of these hospitals from PCI facilities that results in the differences in STEMI management, however there may be other factors that influence the timing of angiography and primary PCI. Despite differences in management, we did not find any differences in mortality, MACE or major bleeding rates following STEMI between the three different cohorts of hospitals. This is a tribute to the current systems of STEMI care including timely pharmacological reperfusion, appropriate bypass of selected non-interventional hospitals with transfer of patients to interventional centres and use of secondary prevention medication.
This study adds to the growing body of international evidence that the pharmaco-invasive approach is a viable method in STEMI patients who present to hospitals without PCI capabilities. In the New Zealand context, this may mean future resources could be efficiently used in further optimising existing STEMI networks.
Appendix
Appendix Table 1: Outline of data collected for the ANZACS-QI national Routine Information cohort.16
Appendix Table 2: Proportion of STEMI reperfusion strategies between hospital groupings. Data collected from the ANZACS-QI registry between 1 September 2013–30 November 2016.
Appendix Table 3: List of New Zealand public hospitals that receive STEMI patients, with and without access to cardiac catherisation services.
Summary
Abstract
Aim
Primary percutaneous coronary intervention (PCI) is the optimal reperfusion strategy to manage ST-elevation myocardial infarction (STEMI). Where timely primary PCI cannot be achieved, an initial pharmacological reperfusion strategy is recommended with subsequent transfer to a PCI-capable hospital. The study aim was to assess STEMI outcomes according to the interventional capability of the New Zealand hospital to which patients initially present.
Method
Nine thousand four hundred and eighty-eight New Zealand patients, aged 20–79 years, admitted with STEMI to a public hospital were identified. Patients were categorised into three groups—metropolitan hospitals with all-hours access to primary PCI (routine primary PCI cohort), metropolitan hospitals without routine access to PCI, and rural hospitals. The primary outcome was all-cause mortality. Secondary outcomes were major adverse cardiac events (MACE) and major bleeding.
Results
Invasive coronary angiography was more frequent in the routine primary PCI cohort compared to metropolitan hospitals without routine access to PCI and rural hospitals (90.6 vs 83.0 vs 85.0% respectively; p<0.001) and occurred more commonly on the day of admission (78.9 vs 28.7 vs 25.7% respectively; p<0.001). There were no differences in multivariable adjusted all-cause mortality, MACE or major bleeding between patients admitted to any of the hospital groupings.
Conclusion
Outcomes after STEMI in New Zealand are similar regardless of the interventional capability of the hospital where they first present.
Author Information
Acknowledgements
Correspondence
Correspondence Email
Competing Interests
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16. Kerr A, Williams MJ, White H, et al. The All New Zealand Acute Coronary Syndrome Quality Improvement Programme: Implementation, Methodology and Cohorts (ANZACS-QI 9). N Z Med J. 2016; 129:23–36.
17. Quan H, Li B, Couris CM, et al. Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am J Epidemiol. 2011; 173:676–82.
18. Kerr AJ, Lee M, Jiang Y, et al. High level of capture of coronary intervention and associated acute coronary syndromes in the all New Zealand acute coronary syndrome quality improvement cardiac registry and excellent agreement with national administrative datasets (ANZACS-QI 25). N Z Med J. 2019; 132:19–29.
19. Kerr A, Exeter D, Hanham G, et al. Effect of age, gender, ethnicity, socioeconomic status and region on dispensing of CVD secondary prevention medication in New Zealand: the Atlas of Health Care Variation CVD cohort (VIEW-1). N Z Med J. 2014; 127:39–69.
20. Ellis C, Gamble G, Devlin G, et al. The management of acute coronary syndrome patients across New Zealand in 2012: results of a third comprehensive nationwide audit and observations of current interventional care. N Z Med J. 2013; 126:36–68.
21. Turk J, Fourny M, Yayehd K, et al. Age-Related Differences in Reperfusion Therapy and Outcomes for ST-Segment Elevation Myocardial Infarction. J Am Geriatr Soc. 2018; 66:1325–1331.
22. Yudi MB, Jones N, Fernando D, et al. Management of Patients Aged ≥85 Years With ST-Elevation Myocardial Infarction. Am J Cardiol. 2016; 118:44–8.
23. Khera S, Kolte D, Palaniswamy C, et al. ST-elevation myocardial infarction in the elderly--temporal trends in incidence, utilization of percutaneous coronary intervention and outcomes in the United States. Int J Cardiol. 2013; 168:3683–90.
24. Forman DE, Chen AY, Wiviott SD, et al. Comparison of outcomes in patients aged <75, 75 to 84, and ≥85 years with ST-elevation myocardial infarction (from the ACTION Registry-GWTG). Am J Cardiol. 2010; 106:1382–8.
25. Yudi MB, Hamilton G, Farouque O, et al. Trends and Impact of Door-to-Balloon Time on Clinical Outcomes in Patients Aged <75, 75 to 84, and ≥85 Years With ST-Elevation Myocardial Infarction. Am J Cardiol. 2017; 120:1245–1253.
26. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet. 2003; 361:13–20.
27. Siontis KC, Barsness GW, Lennon RJ, et al. Pharmacoinvasive and Primary Percutaneous Coronary Intervention Strategies in ST-Elevation Myocardial Infarction (from the Mayo Clinic STEMI Network). Am J Cardiol. 2016; 117:1904–10.
28. Rashid MK, Guron N, Bernick J, et al. Safety and Efficacy of a Pharmacoinvasive Strategy in ST-Segment Elevation Myocardial Infarction: A Patient Population Study Comparing a Pharmacoinvasive Strategy With a Primary Percutaneous Coronary Intervention Strategy Within a Regional System. JACC Cardiovasc Interv. 2016; 9:2014–2020.
29. Armstrong PW, Gershlick AH, Goldstein P, et al. Fibrinolysis or primary PCI in ST-segment elevation myocardial infarction. N Engl J Med. 2013; 368:1379–87.
30. Larson DM, Duval S, Sharkey SW, et al. Safety and efficacy of a pharmaco-invasive reperfusion strategy in rural ST-elevation myocardial infarction patients with expected delays due to long-distance transfers. Eur Heart J. 2012; 33:1232–40.
31. Sim DS, Jeong MH, Ahn Y, et al. Pharmacoinvasive Strategy Versus Primary Percutaneous Coronary Intervention in Patients With ST-Segment-Elevation Myocardial Infarction: A Propensity Score-Matched Analysis. Circ Cardiovasc Interv. 2016; 9.
32. Pu J, Ding S, Ge H, et al. Efficacy and Safety of a Pharmaco-Invasive Strategy With Half-Dose Alteplase Versus Primary Angioplasty in ST-Segment-Elevation Myocardial Infarction: EARLY-MYO Trial (Early Routine Catheterization After Alteplase Fibrinolysis Versus Primary PCI in Acute ST-Segment-Elevation Myocardial Infarction). Circulation. 2017; 136:1462–1473.
33. Danchin N, Puymirat E, Steg PG, et al. Five-year survival in patients with ST-segment-elevation myocardial infarction according to modalities of reperfusion therapy: the French Registry on Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) 2005 Cohort. Circulation. 2014; 129:1629–36.
34. Siddiqi TJ, Usman MS, Khan MS, et al. Meta-Analysis Comparing Primary Percutaneous Coronary Intervention Versus Pharmacoinvasive Therapy in Transfer Patients with ST-Elevation Myocardial Infarction. Am J Cardiol. 2018; 122:542–547.
35. Williams MJ, Harding SA, Devlin G, et al. National variation in coronary angiography rates and timing after an acute coronary syndrome in New Zealand (ANZACS-QI 6). N Z Med J. 2016; 129:66–78.
36. Nixon G, Samaranayaka A, de Graaf B, et al. The impact of a rural scanner in overcoming urban versus rural disparities in the utilisation of computed tomography. Aust J Rural Health. 2015; 23:150–4.
37. Blattner K, Nixon G, Horgan C, et al. Evaluation of a rural primary-referred cardiac exercise tolerance test service. N Z Med J. 2014; 127:63–70.
38. Kerr A, Lee M, Grey C, et al. Acute reperfusion for ST-elevation myocardial infarction in New Zealand (2015-2017): patient and system delay (ANZACS-QI 29). N Z Med J. 2019; 132:41–59.
39. Kerr A. Fibrinolysis for STEMI in New Zealand Public Hospitals July 2015-June 2017 - an ANZACS-QI Registry Report. [In Press].
40. Huynh LT, Rankin JM, Tideman P, et al. Reperfusion therapy in the acute management of ST-segment-elevation myocardial infarction in Australia: findings from the ACACIA registry. Med J Aust. 2010; 193(9):496–501.
41. Li X, Murugiah K, Li J, et al. Urban-Rural Comparisons in Hospital Admission, Treatments, and Outcomes for ST-Segment-Elevation Myocardial Infarction in China From 2001 to 2011: A Retrospective Analysis From the China PEACE Study (Patient-Centered Evaluative Assessment of Cardiac Events). Circ Cardiovasc Qual Outcomes. 2017; 10.
42. Tang EW, Wong CK, Herbison P. Community hospital versus tertiary hospital comparison in the treatment and outcome of patients with acute coronary syndrome: a New Zealand experience. N Z Med J. 2006; 119:U2078.
43. Yong CM, Abnousi F, Asch SM, Heidenreich PA. Socioeconomic inequalities in quality of care and outcomes among patients with acute coronary syndrome in the modern era of drug eluting stents. J Am Heart Assoc. 2014; 3:e001029.
44. Fabreau GE, Leung AA, Southern DA, et al. Area Median Income and Metropolitan Versus Nonmetropolitan Location of Care for Acute Coronary Syndromes: A Complex Interaction of Social Determinants. J Am Heart Assoc. 2016; 5.
45. Fabreau GE, Leung AA, Southern DA, et al. Sex, socioeconomic status, access to cardiac catheterization, and outcomes for acute coronary syndromes in the context of universal healthcare coverage. Circ Cardiovasc Qual Outcomes. 2014; 7:540–9.
46. Hyun K, Redfern J, Woodward M, et al. Socioeconomic Equity in the Receipt of In-Hospital Care and Outcomes in Australian Acute Coronary Syndrome Patients: The CONCORDANCE Registry. Heart Lung Circ. 2018; 27:1398–1405.
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Outcomes after ST-elevation myocardial infarction presentation to hospitals with or without a routine primary percutaneous coronary intervention service (ANZACS-QI 46)
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When a patient presents with an ST-elevation myocardial infarction (STEMI), acute reperfusion therapy by either acute percutaneous coronary intervention (primary PCI) or fibrinolysis improves outcomes.1,2 When it can be performed in a timely fashion primary PCI is the preferred approach;3 however, in all other cases current guidelines from the European Society of Cardiology and the American Heart Association advocate that fibrinolysis followed by early PCI is the recommended strategy for STEMI patients with symptom onset less than 12 hours who cannot be transferred to undergo PCI within 120 minutes.3,4 This recommendation is reflected in local guidelines from the New Zealand Branch of the Cardiac Society of Australia and New Zealand (CSANZ)5 and the National Out-of-Hospital STEMI Pathway co-developed by the National Cardiac Network and New Zealand ambulance services.6 The CSANZ guidelines further note that all STEMI patients with successful reperfusion via fibrinolysis should be transferred to a PCI-capable hospital for rescue PCI if appropriate, or invasive coronary angiography ±PCI within 3–24 hours after fibrinolytic therapy.
There are 47 public hospitals that receive STEMI patients in New Zealand, but only nine of these have round-the-clock access to interventional cardiac catheterisation laboratories allowing participation in a routine primary PCI service.7 When acute reperfusion is considered, each of the 38 remaining hospitals and their ambulance service, without local access to primary PCI, must decide whether to pursue a reperfusion strategy of primary PCI (via transfer to a PCI capable hospital without fibrinolysis), or an approach of fibrinolysis by pre-hospital providers or the in-hospital team, followed by a transfer to a PCI-capable hospital for further definitive PCI.8 This is often termed the ‘pharmaco-invasive’ strategy.9,10 These 38 remaining hospitals can be grouped according to their level of service provision into metropolitan hospitals without routine PCI, and rural hospitals. While two of the metropolitan hospitals, Tauranga and Nelson, without routine PCI have a “mixed” service with limited primary PCI availability on certain times and days of the week only, the others have no on-site interventional service. The hospitals without local PCI capability predominantly serve regional or rural communities.11 Rural hospitals specifically differ from the metropolitan hospitals with or without routine access to PCI, in that they are predominately staffed by generalist doctors and nurses without any local specialist support12–14 and have limited access to both basic and advanced diagnostic tests as well as resources such as acute cardiac care unit facilities.15 The potential for both variation in clinical practice and varying thresholds for angiography referral, together with the greater delays to invasive coronary angiography in patients requiring transfer for angiography might adversely affect outcomes following STEMI in these patients.
The aim of this observational cohort study was to assess the outcomes for patients with STEMI according to whether they first present to a metropolitan hospital with a routine all-hours primary PCI service, a metropolitan hospital without routine primary PCI, or to a rural hospital.
Methods
Patient cohorts and data collection
The All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) programme is a clinician-led initiative which aims to advocate for appropriate management of acute coronary syndrome (ACS) patients and to close the gap between evidence-based treatment and daily clinical practice.16 Data sources for the ANZACS-QI programme include the ANZACS-QI registry which collects an in-depth dataset on the limited subset of ACS patients who have a coronary angiogram (approximately 60% of all ACS patients nationwide), and the National administrative datasets which collects limited data for all hospitalisations for ACS and its sub-types recorded using the International Statistical Classification of Diseases and Related Health Problem (ICD10) coding as well as coronary procedure codes. A principle strength of the National datasets are that they collect standardised demographic and clinical data for all New Zealand residents who are admitted to public hospitals.16 To report the burden of non-cardiac comorbidity, we modified the Charlson comorbidity index17 by excluding congestive heart failure. Data from the ANZACS-QI registry has been used to validate the accuracy of the National administrative dataset ACS sub-types (STEMI, NSTEMI, UA) and procedure codes.18 From the National datasets, we identified all confirmed STEMI cases in New Zealand resident patients between 20–79 years of age who presented to a New Zealand public hospital between November 2011–November 2016. Both primary and secondary STEMI diagnostic codes were used. For this analysis we used only the first admission with a STEMI during the time period. This search method was validated against the ANZACS-QI registry to ensure accuracy.18 Post-STEMI mortality, hospitalisation and medication dispensing data were individually linked from mortality and pharmaceutical collections.19 Secondary prevention medications dispensed within three months of hospital discharge are reported. Appendix Table 1 shows the types of data collected in these respective databases.
Patients who present with STEMI can be rapidly transferred between hospitals to undergo appropriate management. We thus applied a previously validated process to “bundle” ACS hospitalisations to ensure a temporally continuous admission under a single index admission episode of care.20 Patients were divided depending on the local STEMI services provided by the hospital that first received the patient.
Patients 80 years and older were excluded. They are a heterogenous group that contribute to a minority of cases (6.1–6.5%), often have comorbidity requiring more individualised treatment decisions, and have disproportionately high rates of mortality (19.8–75%).21–25
Hospital cohorts
Hospitals were divided into three different cohorts with differing STEMI management policies. They were—metropolitan hospitals with routine all-hours access to primary PCI service for STEMI (“routine primary PCI” cohort), metropolitan hospitals that do not provide a routine primary PCI service (“metropolitan without routine PCI” cohort) and mostly provide a pharmaco-invasive strategy (two of these hospitals, Tauranga and Nelson, provide primary PCI at certain times and days of the week) and rural hospitals that also predominately pursue a pharmaco-invasive strategy. These hospital groupings are supported by ANZACS-QI registry data over a similar time period that confirms the dominant management strategies for each cohort (Appendix Table 2). A list of New Zealand hospitals with and without access to routine all-hours primary PCI services are listed in Appendix Table 3.
STEMI management pathways
Patients were managed according to prevailing guidelines.5,6 Patients who presented with STEMI who were clinically eligible for acute reperfusion therapy received either primary PCI or fibrinolysis. Those with a delayed presentation of greater than 12 hours of symptoms, or in whom acute reperfusion was considered clinically inappropriate due to comorbidities received medical therapy only. Those undergoing primary PCI received a loading dose of anti-platelet medications and proceeded to the cardiac catheterisation laboratory for invasive coronary angiography and PCI. Patients undergoing the pharmaco-invasive approach typically received a loading dose of aspirin or another anti-platelet agent and received pharmacological fibrinolysis with bolus intravenous tenecteplase. Patients were then routinely transferred to another hospital with PCI capabilities in order to receive an early invasive coronary angiography and PCI if appropriate. Patients who underwent fibrinolysis which resulted in less than 50% resolution of the elevated ST segment at 60 minutes after fibrinolysis, or recurrence of ST elevation, or ongoing ischemic symptoms, or continuing haemodynamic instability were defined as failed fibrinolysis and were urgently transferred for rescue PCI.
Clinical end points and definitions
Outcomes were available from hospital admission to the end of 2017, to ensure each patient had a minimum possible follow-up of one year. The primary outcome measured was all-cause mortality. The two secondary outcomes were 1) a composite of all major adverse cardiac events (MACE), comprising of a composite of all-cause mortality, myocardial re-infarction, ischaemic or haemorrhagic stroke and new heart failure, and 2) the rate of fatal and non-fatal major bleeding.
Re-infarction, ischaemic stroke, hemorrhagic stroke and heart failure were defined by their respective ICD-10 definitions. Fatal and non-fatal major bleeding were defined by the ICD-10 code for “fatal bleeding”, a primary ICD-10 code for bleeding or a secondary ICD-10 code for bleeding requiring transfusion.
Statistical analysis
Categorical variables were summarised as frequency and percentage. Pearson’s chi-square test was used to compare different types of hospitals. Continuous variables were presented as mean and standard deviation (SD) and/or median with interquartile range (IQR), and the comparisons between types of hospitals were done using nonparametric Mann-Whitney U test as the continuous data was not normally distributed.
Cox proportional hazard regression models were constructed to estimate the hazard ratios and 95% confidence interval for the outcomes after ensuring that the assumption of proportional hazards was met.
All P-values reported were two tailed and a P-value <0.05 was considered significant. Data were analysed using SAS statistical package, version 9.4 (SAS Institute, Cary, NIC). Outcomes were displayed using Kaplan-Meier survival curves using R Studio.
Ethics approval
ANZACS-QI is part of the wider Vascular Informatics Using Epidemiology and the Web (VIEW) study. The VIEW study was approved by the Northern Region Ethics Committee in 2003 (AKY/03/12/314), with subsequent amendments to include the ANZACS-QI registries, and with annual approvals by the National Multi-region Ethics Committee since 2007 (MEC07/19/EXP).
Results
We identified 13,265 records from patients that presented with a STEMI to a New Zealand hospital between 1 November 2011 to 30 November 2016. Of these, 201 records were non-New Zealand residents, 39 had missing socioeconomic data and 2,955 were outside the stated age bracket of 20–79 years old. Five hundred and eighty-two records were for patients identified to have presented with a repeated STEMI episode during the study period. Thus, a total of 9,488 eligible patients participated in the study.
Six thousand one hundred and seventy-nine participants first presented to a metropolitan hospital providing a routine all-hours primary PCI service (routine primary PCI cohort), 2,801 participants first presented to a metropolitan hospital that does not provide a routine primary PCI service (metropolitan without routine PCI cohort) and 508 participants first presented to a rural hospital that does not provide a routine primary PCI service (rural hospital cohort).
Baseline characteristics (Table 1)
Patients presenting to the metropolitan without routine PCI and rural hospital cohort were older, more likely to be female and of Māori ethnicity than patients presenting to a routine primary PCI hospital.
Table 1: Baseline patient characteristics.
The hospitals without access to a routine primary PCI service received a larger proportion of patients who lived in socioeconomically deprived areas. 32.0% of patients in the metropolitan without routine PCI cohort and 28.4% patients in the rural hospital cohort were from the most deprived quintile (NZ Dep13, 9–10) compared to 22.8% of patients in the routine primary PCI cohort. The reciprocal was also true where a larger proportion of patients from the most affluent quintile (NZDep13, 1–2) were initially seen in hospitals of the routine primary PCI cohort.
Prior cardiovascular disease, myocardial infarction, congestive heart failure, PCI and the modified non-cardiac Charlson comorbidity score17 were comparable among the three hospital cohorts. The prevalence of prior CABG was slightly higher within the metropolitan without routine PCI cohort (p=0.045).
Coronary procedures and timing (Table 2)
Eight thousand three hundred and fifty-two (88%) of the 9,488 study participants proceeded for invasive coronary angiography. More patients in the routine primary PCI hospital cohort had angiography during their admission (90.6%) compared to the metropolitan hospital without routine PCI cohort (83.0%), and rural hospital cohort (85.0%) (p<0.001). Of those that proceeded for invasive coronary angiography during the index admission, 91.6% of patients in the routine primary PCI cohort received PCI or CABG surgery during their index admission compared to 80.0% of patients in the metropolitan hospital without routine PCI cohort, and 79.6% in the rural hospital cohort (p<0.001).
Table 2: Angiography, percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) time intervals and rates of medical therapy.
Of those undergoing angiography, more patients presenting to a routine primary PCI hospital (78.9%) received invasive coronary angiography within the first 24 hours of presentation than those to a metropolitan hospital without routine PCI (28.7%), or a rural hospital (25.7%) (p<0.001). Only 13.2% of patients presenting to a routine primary PCI hospital had angiography 24–72 hours after presentation compared to 42.0% of those presenting to a metropolitan without routine PCI hospital, and 46.3% of those to a rural hospital. 7.9% of patients in the routine PCI hospital cohort had invasive coronary angiography beyond 72 hours after presentation compared to 29.3% and 28.0% of the metropolitan without routine PCI, and rural hospital cohorts.
Secondary prevention medications dispensed post-discharge (Table 2)
The dispensing of secondary prevention medications was high across groups but with a slightly lower use of anti-platelet agents and ACEI/ARBs in the non-routine primary PCI groups.
Outcomes (Figures 1,2 and Table 3)
The average follow-up duration for all-cause mortality, was 3.03 years. The all-cause mortality, MACE and major bleeding outcomes are shown using Kaplan Maier survival plots in Figures 1 and 2. The Kaplan-Maier mortality at one and three years was 11.7% and 16.6% for patients presenting to the metropolitan with routine PCI cohort, 12.2% and 16.2% for metropolitan hospitals without routine PCI and 12.6% and 18.7% for rural hospitals.
Figure 1: All-cause mortality.
Figure 2: A) All-cause mortality/non-fatal MI/HF/stroke (MACE); B) fatal/non-fatal bleeding.
The Kaplan-Maier MACE at one and three years was 22.0% and 30.1% for patients presenting to the metropolitan with routine PCI cohort, 24.4% and 31.9% for metropolitan hospitals without routine PCI and 21.5% and 31.0% for rural hospitals.
The Kaplan-Maier major bleeding at one and three years was 6.9% and 8.6% for patients presenting to the metropolitan with routine PCI cohort, 7.5% and 9.1% for metropolitan hospitals without routine PCI and 5.5% and 7.1% for rural hospitals.
After adjusting for age, sex, ethnicity, deprivation score, modified Charlson score and prior CVD, there were no differences in outcomes for patients admitted to each of the three hospital groups (Table 3).
Table 3: Outcomes.
Discussion
This nationwide, real-world study describes the interventional management and outcomes for all hospitalised STEMI patients in New Zealand according to the interventional capability of the hospitals to which they were first admitted. Patients presenting first to a routine primary PCI capable hospital, as opposed to a metropolitan without routine PCI, or a rural hospital, received slightly higher overall rates of coronary angiography and revascularisation and received these more quickly. Of those treated with PCI who presented first to a routine primary PCI capable hospital, nearly four in five received PCI on the day of admission, compared to a quarter of those presenting to other hospitals. Despite the differences in management, all clinical outcomes over a mean of three years follow-up did not differ between patients presenting to each of the three hospital groupings.
Efficacy of reperfusion strategies
This finding is congruent with previous literature examining different STEMI management strategies. Patients who are reperfusion candidates presenting with STEMI to New Zealand hospitals providing all-hours routine primary PCI services proceed for invasive coronary angiography with an aim for performing primary PCI. Reperfusion candidates presenting with STEMI to hospitals without local PCI facilities are transferred to receive primary PCI where possible. However, in most cases a transfer cannot be completed within an appropriate time period (120 minutes) and patients then are administered fibrinolytic therapy as the immediate reperfusion strategy prior to transfer to a hospital with PCI facilities for invasive coronary angiography ± PCI. This strategy is commonly called the pharmaco-invasive approach.9,10
Over the preceding decades, it has been established that primary PCI delivers superior outcomes compared to pharmacological fibrinolysis monotherapy.26 However, despite the delay in accessing PCI inherent within the pharmaco-invasive approach, there is similar efficacy to primary PCI. In a registry study from the Mayo Clinic STEMI network comparing the rates of all-cause mortality between patients undergoing the pharmaco-invasive approach versus primary PCI, showed that the rates of early and late mortality were comparable between the two strategies.27 In a study from the University of Ottawa Heart institute regional STEMI system which employs a policy of primary PCI for patients presenting within a 90km radius of the PCI centre and a pharmaco-invasive strategy for those outside this limit28 displayed the rates of mortality, stroke or reinfarction were no different between the two strategies. The landmark Strategic Reperfusion Early After Myocardial Infarction (STREAM) trial29 assigned STEMI patients to undergo primary PCI versus fibrinolysis with transfer to a PCI capable hospital for a coronary angiography within 6–24 hours. The rate of the 30-day primary endpoint, a composite of death, shock, CHF and reinfarction, was similar among both groups. Other studies have noted similar findings.30–33 Lastly, a meta-analysis consisting of studies up to 201734 have concluded there is no difference in short-term and long-term mortality between the two reperfusion strategies as long as symptom onset to device time in primary PCI did not exceed 200 minutes.
Timing of angiography
A prominent finding in our results is the delay in proceeding for angiography for patients presenting to rural and metropolitan hospitals with no routine PCI available. 28.7% of metropolitan hospitals without PCI, and 25.7% of the rural hospital cohort were able to access invasive angiography within 24 hours. This contrasts with 78.9% of patients who presented to hospitals providing routine primary PCI proceeding to invasive angiography within 24 hours.
The New Zealand Cardiac Clinical Network and the Ministry of Health recommend a “three-day door-to-catheter target” for all acute coronary syndrome (including unstable angina, NSTEMI and STEMI) admissions.35 The Cardiac Society of Australia and New Zealand recommends all STEMI patients with successful reperfusion via fibrinolysis should be transferred to a PCI capable hospital for cardiac catherisation within 24 hours after fibrinolytic therapy.5 While our study was unable to determine when the transfer to a PCI centre took place, it showed that only one-quarter of patients who present to a rural or metropolitan hospital with no routine primary PCI had angiography within this 24-hour window. This finding is similar to a nationwide audit in 2012 that showed 22% of patients presenting with STEMI to non-interventional hospitals received routine angiography within 24 hours.20 Nearly one-third of patients who present to a rural or metropolitan hospital with no routine primary PCI were awaiting cardiac catheterisation more than 72 hours post-STEMI.
Delays in in receiving angiography primarily reflect shortfalls in processes to ensure early transfer of patients to an interventional hospital together with appropriate prioritisation on arrival. This has previously been noted in a New Zealand study which reported that patients are more likely to wait longer for cardiac catherisation in districts without interventional facilities after ACS.35 New Zealand has a small and geographically dispersed population with smaller regional and rural centres. These hospitals do not have the concentration of healthcare resources and specialist care as seen in hospitals with a routine primary PCI service. Instead, metropolitan hospitals without routine primary PCI and rural hospitals are more likely to be served by general physicians in metropolitan hospitals or generalist rural hospital doctors in rural hospitals13 leading to a range of inter-physician differences in the threshold for referrals, delays in transfer and proceeding for cardiac catherisation. Reduced rates of investigations (eg, ETT, CT scans) for geographically isolated areas has been demonstrated previously in New Zealand.36,37 The optimal management of STEMI involves prompt inter-disciplinary and inter-regional co-operation and co-ordination among frontline ambulance staff, helicopter crews, STEMI co-ordinators, rural nurses, general practitioners, general and emergency physicians, cardiac catherisation laboratory staff and interventional cardiologists. Any misaligned communication or expectations within this chain of care results in prolonged times from first medical contact to crossing of the coronary occlusion or stenosis with a wire. It has been recognised that it is essential to implement standardised pathways for management to reduce uncertainty and inequality nationwide. This has resulted in the New Zealand out-of-hospital STEMI pathway in 2016.6
Differences in rates of angiography and revascularisation
There were lower rates of invasive coronary angiography in patients presenting to hospitals without routine primary PCI services. Patients in these cohorts were slightly less likely to receive invasive coronary angiography during their admission, with 83–85% proceeding for cardiac catheterisation compared to 90.6% of patients presenting to hospitals providing a routine all-hours primary PCI service. This may be contributed by the different baseline characteristics of the three cohorts, in particular the older age of the non-routine PCI hospital cohorts. Among patients who did have a diagnostic angiogram, the gap for revascularisation was even greater; 91.6% of these patients in the routine primary PCI group received revascularisation by either PCI or CABG during their index admission compared to 80.0% of patients in the metropolitan hospitals without routine PCI cohort and 79.6% in the rural hospital groups. This is likely in part due to a higher rate of non-obstructive coronary artery disease in those already treated with fibrinolytic therapy, which may have lysed the thrombus who therefore do not need revascularisation.38
Rural-urban differences
Although we have primarily created hospital cohorts based on STEMI management capabilities, these groups also represent a rural-urban divide. Hospitals providing routine primary PCI are located within the largest metropolitan centres, whereas hospitals of the non-routine PCI cohorts are in regional urban areas and rural communities. We previously reported that ≥80% of patients with STEMI who lived in predominantly rural district health boards (DHBs) received pharmaco-invasive therapy.39 Patients who presented to metropolitan hospitals without routine PCI and rural hospitals were more likely to be older, female, from a more deprived socioeconomic quintile and of Māori or European ethnicity. After adjustment, there were no significant differences in outcomes between patients initially presenting to a rural compared with a routine primary PCI hospital. This is congruent with previous Australian40 and Chinese studies41 which found that there was no difference in mortality post STEMI between metropolitan and rural regions. This study shows that great progress has been made in New Zealand over the last two decades with a closing of the gap, especially for mortality, in outcomes and access to intervention between hospitals with PCI and those without.42 It is a concern that patients presenting to non-primary PCI hospitals tended to have greater levels of socioeconomic deprivation. Delays in angiography associated with location of care and socioeconomic status have been demonstrated previously in a study in the US.43 Most other studies have examined the broader topic of acute coronary syndrome, with varied findings. In Canada, patients who presented with ACS from non-metropolitan areas were less likely to receive cardiac catheterisation within one day and those from the lowest income area within non-metropolitan areas were less likely to have a coronary angiogram within seven days compared to their more affluent counterparts living in metropolitan areas.44 Also, women from poor-income neighbourhoods were associated with a poorer odds of having coronary angiography and a higher mortality within 30 days.45 In contrast, a study in Australia found that socioeconomic status was not related to differences in having coronary angiography after ACS.46
Safety outcomes
There was no statistically significant difference in major bleeding between the three cohorts. There was a small, but significant, increase in haemorrhagic stroke within the metropolitan without routine PCI cohort (Table 2). The literature is varied when examining the safety aspects of the pharmaco-invasive strategy. Two studies28,29 demonstrated increased rates of haemorrhagic stroke with the pharmaco-invasive method. This increased safety risk was found to be confined to patients greater than 75 years of age in a sub-analysis of one study.29 This has led to the recommendation to use lower dose bolus fibrinolytic therapy in patients greater than 75 years of age.
Limitations
We compared practice and outcomes according to which three types of hospital a patient initially presented to. Hospitals were categorised according to their levels of availability of primary PCI services and access to specialist services. Although each hospital has defined reperfusion policies, STEMI management is not necessarily consistent for each hospital within these three groups. ANZACS-QI data shows that 10.5–14% of patients who present to hospitals that do not provide a routine primary PCI service do indeed proceed for primary PCI (Appendix Table 2). The most prominent example of this are a subset of hospitals such as Tauranga or Nelson Hospital who offer primary PCI within limited hours or within the limits of staffing availability. In some regions a small number of patients are flown directly to a PCI capable centre for primary PCI and so may bypass their local hospital. In addition to the effect of acute reperfusion therapy, outcomes are also likely to be dependent on the other components of the STEMI pathway management including pharmacological management, pre-hospital vs in-hospital fibrinolysis and the availability of appropriate and timely transfer to tertiary centres. These may also vary between hospitals within our three service groups. Furthermore, the national datasets used in this study do not reliably record whether patients were treated with acute reperfusion as primary PCI and fibrinolysis are not coded. Primary PCI cases and those receiving fibrinolysis and subsequent angiography can be identified using the separate ANZACS-QI registry16,38 but there is no data source which reliably identifies patients treated with fibrinolysis who do not proceed to an angiogram. A consequence of this is that for hospitals without routine primary PCI availability we cannot reliably report the proportion of STEMI patients who do not receive acute reperfusion therapy. We were also unable to capture any patient who died without reaching a hospital or who died after STEMI discharge outside of New Zealand.
Conclusion
Our study has demonstrated that patients who present with STEMI to hospitals without a routine primary PCI service are less likely to receive coronary angiography, wait longer for angiography and are less likely to receive coronary revascularisation. This is likely due to the geographical isolation of these hospitals from PCI facilities that results in the differences in STEMI management, however there may be other factors that influence the timing of angiography and primary PCI. Despite differences in management, we did not find any differences in mortality, MACE or major bleeding rates following STEMI between the three different cohorts of hospitals. This is a tribute to the current systems of STEMI care including timely pharmacological reperfusion, appropriate bypass of selected non-interventional hospitals with transfer of patients to interventional centres and use of secondary prevention medication.
This study adds to the growing body of international evidence that the pharmaco-invasive approach is a viable method in STEMI patients who present to hospitals without PCI capabilities. In the New Zealand context, this may mean future resources could be efficiently used in further optimising existing STEMI networks.
Appendix
Appendix Table 1: Outline of data collected for the ANZACS-QI national Routine Information cohort.16
Appendix Table 2: Proportion of STEMI reperfusion strategies between hospital groupings. Data collected from the ANZACS-QI registry between 1 September 2013–30 November 2016.
Appendix Table 3: List of New Zealand public hospitals that receive STEMI patients, with and without access to cardiac catherisation services.
Summary
Abstract
Aim
Primary percutaneous coronary intervention (PCI) is the optimal reperfusion strategy to manage ST-elevation myocardial infarction (STEMI). Where timely primary PCI cannot be achieved, an initial pharmacological reperfusion strategy is recommended with subsequent transfer to a PCI-capable hospital. The study aim was to assess STEMI outcomes according to the interventional capability of the New Zealand hospital to which patients initially present.
Method
Nine thousand four hundred and eighty-eight New Zealand patients, aged 20–79 years, admitted with STEMI to a public hospital were identified. Patients were categorised into three groups—metropolitan hospitals with all-hours access to primary PCI (routine primary PCI cohort), metropolitan hospitals without routine access to PCI, and rural hospitals. The primary outcome was all-cause mortality. Secondary outcomes were major adverse cardiac events (MACE) and major bleeding.
Results
Invasive coronary angiography was more frequent in the routine primary PCI cohort compared to metropolitan hospitals without routine access to PCI and rural hospitals (90.6 vs 83.0 vs 85.0% respectively; p<0.001) and occurred more commonly on the day of admission (78.9 vs 28.7 vs 25.7% respectively; p<0.001). There were no differences in multivariable adjusted all-cause mortality, MACE or major bleeding between patients admitted to any of the hospital groupings.
Conclusion
Outcomes after STEMI in New Zealand are similar regardless of the interventional capability of the hospital where they first present.
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Outcomes after ST-elevation myocardial infarction presentation to hospitals with or without a routine primary percutaneous coronary intervention service (ANZACS-QI 46)
When a patient presents with an ST-elevation myocardial infarction (STEMI), acute reperfusion therapy by either acute percutaneous coronary intervention (primary PCI) or fibrinolysis improves outcomes.
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