Cardiovascular disease remains the leading cause of death globally at 31% in 2012.1 In New Zealand, cardiovascular disease accounted for 33% of all deaths in 2013.2 Diagnosis and management of patients with an acute coronary syndrome (ACS) has markedly evolved over the last 20 years. Local and international guidelines have summarised these improvements.3–5 Some important milestones include the improvements in the range of antithrombotic therapy, the utility of cardiac troponins and the improvements in invasive and reperfusion strategies, especially in the acute setting of ST-elevation myocardial infarction (STEMI).

Audits of suspected ACS admissions were undertaken in New Zealand in 20026 and 2007,7 and across Australia and New Zealand in 2012,8,9 allowing a longitudinal review of these ACS patients and the quality of their care over a 10-year period. We reviewed the characteristics, management and in-hospital outcomes of STEMI patients from these three ACS cohorts.

Methods

Study population and centres

The three audits were conducted by the New Zealand ACS Audit Group (which consisted of one or more cardiologists or general physicians from all public hospitals in New Zealand admitting ACS patients). The number of centres increased from 36 in 2002 to 39 in each of 2007 and 2012. Detailed methodology of how each audit was undertaken has been previously reported.6–9 In brief, all patients admitted to hospital overnight with a suspected or definite ACS during the study period of two weeks in mid-May of 2002, 2007 and 2012 were included. This study reports the subgroup of patients with a discharge diagnosis of STEMI.

There has been a small growth in the number of centres with the capacity for PCI during this decade. The number of interventional and non-interventional centres as defined in these studies was eight and 28 respectively in 2002, nine and 30 in 2007 and 10 and 29 in 2012 (Table 1). Hospitals which admitted suspected ACS patients, but did not have onsite coronary angiogram facilities in any of the three audits were: Kaitaia, Dargaville, Rawene, Kawakawa, Whangarei, Waitakere, Thames, Whakatane, Rotorua, Tokoroa, Te Kuiti, Taupo, Gisborne, Taumarunui, Wanganui, Masterton, Hutt, Blenheim, Greymouth, Ashburton, Timaru, Oamaru, Clyde and Invercargill hospitals.

Table 1: Hospital angiogram and PCI availability during each of the audits.

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Hospitals in bold: Regional centre with service available 24 hours, seven days.

++ Hospital service available during the working week.
+ Hospital service available several days a week.
Hospitals shown in brackets had only one PCI operator at the time of the audit, hence not defined as “Intervention Centre”.
Y=Yes, N=No, (P)=Private hospital, PCI= percutaneous intervention Cath=Catheter laboratory.

Reperfusion-eligible STEMI patients and major comorbidities

Reperfusion eligible STEMI patients are those who present with >20 minutes of ischaemic chest pain, with ST-segment elevation of >1mm, in two contiguous leads, or >2mm in leads V1 to V3 (>1.5mm for women), or left bundle branch block not known to be old, <12 hours of pain onset or <24 hours if there is continuing ischaemic symptoms or haemodynamic compromise. Relative contraindications to fibrinolytic therapy and/or primary PCI need to considered.3–5

In the 2002 and 2007 audits,6,7 a subjective clinical assessment was made to indicate major comorbidities which might discourage invasive management, and included (but were not limited to) significant renal failure, prior CVA/Dementia, significant pulmonary disease and significant cancer. In the 2012 audit,8,9 major bleeding and chronic liver disease were added to this list.

Data collection

Study protocols, case report forms and definitions of variables were provided to all centres for all three audits. Demographics, past history, presentation, investigations, treatments and discharge diagnoses were prospectively recorded for each patient’s acute care episode, including hospital transfers. The National Multicentre Ethics Committee decided, after input from all centres, that the New Zealand ACS audits were of health service delivery and consent waiver was applied, allowing collection of National Health Index (NHI) numbers to assist with data collection.10

Statistics

Mean (standard deviation) or median (interquartile range) were used to present continuous variables as indicated, and frequency (percentage) for categorical variables. Wilcoxon/Kruskall Wallis test and Fisher’s exact or chi-squared test as appropriate were used for between group comparisons for continuous and categorical variables. Confidence intervals for rates were calculated using a mid P method (www.openepi.com accessed 31/05/2016). SAS (v9.4, SAS Institute Inc) was used to perform statistical analyses, with all tests being two-tailed, and P<0.05 deemed statistically significant.

Results

Over the 14 day audit periods, similar numbers of patients with STEMI were admitted in the three audits: 2002: n=101, 2007: n=86 and 2012: n=99, a total of 286 patients. Table 2 shows the baseline characteristics. There were no major differences in age, sex or ethnicity across the three groups, with male Caucasians being the largest group of patients. Dyslipidaemia was more frequently reported in the 2012 cohort, and hypertension least frequently reported in the 2007 cohort. There was no difference between the cohorts in the previous history of cardiovascular diseases or interventions.

Table 2: Baseline patient demographic data for STEMI patients 2002, 2007 and 2012.

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CVS: Cardiovascular, MI: Myocardial infarction; PCI: Percutaneous coronary intervention; CABG: Coronary artery bypass grafting; PAD: Peripheral artery disease; TIA: Transient ischaemic attack; AF: Atrial fibrillation. STEMI: ST segment elevation myocardial infarction.

The investigations undertaken and treatments given to STEMI patients are listed in Table 3. There has been a significant increase in patients undergoing echocardiography (from 35% to 70%, P<0.0001) and invasive angiography (31% to 87%, P<0.0001) over time, with fewer patients having exercise tests (18% to 4%, P=0.0026). The acute reperfusion strategy changed with a rise in primary PCI (from 3% to 42%, P<0.0001) and a decrease in fibrinolytic therapy (55% to 31%, P=0.0010). In addition, more patients overall received PCI during their hospital stay (13% to 66%, P<0.0001).

Table 3: Investigations, treatments and mortality of STEMI patients: 2002, 2007 and 2012.

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PCI: Percutaneous coronary intervention; UF: Unfractionated; CABG: Coronary artery bypass graft; ETT: Exercise treadmill test; Echo: Echocardiogram.
* Includes three patients in 2012 with pre-hospital fibrinolysis.
** Neither fibrinolytic therapy nor primary PCI.

There was also an increase in the use of most antiplatelet and anti-thrombotic agents, including aspirin, P2Y12 inhibitors, heparin and IIb/IIIa inhibitors during in-hospital treatment. Discharge medications after STEMI admission are shown in Figure 1. There have been significant increases in the prescription of all five of these evidence-based myocardial infarction medications, particularly marked for a second anti-platelet agent: a P2Y12 inhibitor, from 14% to 98%, (P<0.0001).

Figure 1: Discharge medications of STEMI patients in each audit year with n (%) at each year.

In-hospital mortality did not significantly change, although numbers are small (14 to 7 patients, P=0.17). Length of stay decreased from a median of 5 (4,7) to 3.7 (2.9, 6.1) days (P=0.0084) (Table 3).

Delays to administration of fibrinolytic therapy, primary PCI, rescue PCI and in-hospital angiography are detailed in Table 4. There was no significant decrease in median door to needle times for fibrinolysis between 2002 and 2012 [48 (Q1,Q3: 25,130) v 48 (Q1,Q: 28,84) minutes, P=0.89]. Data on door to device times was not collected in 2002 and 2007. In 2012, the time from door to first device deployment in the infarct artery was <120 minutes in 79% and <90 minutes in 67% of patients. Median delay was 82 (Q1,Q3: 56,93) minutes. Of the five patients undergoing rescue PCI in 2012, the fibrinolysis to device time was 7.1 (Q1,Q3: 5.4, 8.0) hours.

Table 4: Time to reperfusion treatment of STEMI patients: 2002, 2007 and 2012.

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DTNT=Door to needle time; DTDT=Door to device time; PPCI=Primary PCI; Pts=Patients
*Excluding pre-hospital fibrinolysis.

Although there was a reduction in the percentage of patients not receiving any reperfusion therapy (42% to 27% P<0.0001), more than a quarter of STEMI patients in 2012 still did not receive this life-saving treatment. Across all three audits, 190 (67%) of STEMI patients were reperfused (primary PCI or fibrinolysis) compared to 95 (33%) who were not given reperfusion therapy. Reperfused patients were younger, and took less time from symptom onset to presentation to hospital as compared with patients not given reperfusion therapy [7.9 (Q1,Q3: 1.1, 66.8) v 30.4 (Q1,Q3: 19.9, 120), p=0.0008 hours] (Table 5). In multivariable analysis (Figure 2), age >69 years (n=138, 50%)was associated with a two-fold increased likelihood of not being reperfused (OR 2.0 (95% CI 1.12, 3.63) P=0.018). Further, compared to the 220 (83%) patients presenting to ED <12 hours after symptom onset, those who presented >12 hours (n=46 (17%)) had a seven-fold increase in odds of not being reperfused (OR 7.7 (95% CI 3.6, 16.2) P<0.0001. Sex and year of audit did not predict the rate of non-reperfusion (Figure 2).

Table 5: Characteristics of STEMI patients: by audit year and receiving perfusion therapy or not.

* Reperfusion therapy significantly different from no-reperfusion therapy, all P< 0.0007

** P=0.0023

Figure 2: STEMI Patients and reperfusion: Multivariable analysis of odds (95% CI) of not being reperfused.

Discussion

Audits of the number, management and outcome of suspected ACS patients conducted in 2002, 2007 and 2012 in New Zealand allow longitudinal comparisons of the ACS admissions over a decade.6–9 For STEMI patients, baseline demographics largely did not change over time. However, the optimal management of these patients did change, as well as the ability of the medical services to better deliver this management.

Widespread uptake of a rapid invasive interventional strategy is the main change in STEMI management since the first NZACS audit in 2002. The change in preferred reperfusion strategy, from fibrinolytic therapy to primary PCI is very evident. Patients with STEMI who can be brought to a cardiac catheter laboratory within 120 minutes (door to device time) should receive primary PCI.3–5 The alternative management is for patients to receive fibrinolytic therapy, which remains an effective method of reperfusion, and includes pre-hospital fibrinolytic therapy for more remote areas.11 Following fibrinolytic therapy, there then needs to be a routine policy of transfer to a Regional Centre for subsequent invasive coronary angiography and revascularisation embedded in the management plan.12–15 Routinely, patients should be transferred to receive their angiogram within 24 hours. However, those patients who clinically fail to reperfuse by 60 minutes after fibrinolytic therapy is started need to be transferred as an emergency, to allow emergency salvage of myocardium with ‘rescue’ PCI.3–5 Future service improvements, with helicopter rescue for some patients within geographical reach of a PCI centre, will further increase the numbers who access a primary, or rescue, PCI. It is notable that overall more patients received invasive angiography (31% to 87%, P<0.0001) between 2002 and 2012. Further, more were managed with in hospital revascularisation with either PCI or CABG (17% to 72%, P<0.0001).

Despite our findings, there remains room for improvement in the delivery of reperfusion and revascularisation care to STEMI patients. In 2012, the primary PCI rate of 42% is still not optimal. However, a direct comparison of this rate in 2012 in New Zealand is not different from the primary PCI rate in Australia (42% v 37%, P=0.34).16 Ongoing data from the All New Zealand Acute Coronary Syndrome Quality Improvement Programme (ANZACS QI) may show a future increase in patients receiving primary PCI.17

However, a significant number of patients do not receive either reperfusion therapy. This is associated with increased hospital mortality. When patients from across the three New Zealand audit cohorts are combined from 2002, 2007 and 2012 (n=286), the in-hospital mortality without reperfusion therapy was higher: 16.8% v 5.3%, p=0.0024, compared to those patients receiving reperfusion therapy. This is consistent with the findings of the combined 2012 Australia and New Zealand audit of STEMI patients (n=419), which found a mortality increase in hospital: 11.7% v 4.9%, P=0.011 for patients who did not receive reperfusion therapy compared to those who did receive this therapy.18 This important patient group needs further study.

In addition, although we have seen a move away from exercise treadmill testing for inducible ischaemia, towards coronary angiography to define the coronary anatomy, as the method to risk assess a patient, in 2012 still 11% of patients did not receive either test following their STEMI presentation. Although there may be good reasons to not undergo stress testing or coronary angiography, such as a frail elderly patient with major comorbidities, this is unlikely to account for all patients in this subgroup.

Reducing the ischaemia (symptoms) to device time is critical. The determinants are multifactorial, from increasing patient awareness to seek help when symptoms occur, to improving access for transport to interventional centres from around the country.12–15 It is clear that systems of care with streamlined and uniform treatment protocols in the ambulance and hospitals are needed.

Echocardiography is now more frequently performed as recommended in guidelines. It is important for the assessment of left ventricular and valve function, the presence of left ventricular thrombus and of other possible complications of myocardial infarction. However, the availability of this essential cardiological tool is still limited across the country and remains an important deficiency in service provision.19,20

Increased use of anti-platelet therapies is a reflection of both the published evidence base and funding by PHARMAC. The beneficial use of a second antiplatelet P2Y12 inhibitor agent in an ACS was first demonstrated in the original Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial published in 2001,21 with the use of dual anti-platelet therapy for patients receiving a stent becoming an important part of management,3–5 but the uptake was low in our 2002 cohort at only 14%, due to previous funding restrictions.22 A change in PHARMAC policies then allowed this to increase to 73% by 2007. The Platelet Inhibition and Patient Outcomes (PLATO) trial published in 2009 showed ticagrelor to be superior to clopidogrel in ACS with a reduction in mortality.23 Dual antiplatelet therapy of aspirin and either ticagrelor or clopidogrel were prescribed to 98% of the 2012 cohort in accordance with the latest evidence and guidelines.

The prescription rates of all five evidence-based ACS medication classes have increased, reflecting better optimisation of secondary medical prevention therapy over time. Although medical therapy prescription at discharge is near 100% for dual antiplatelet therapy, the 95% rate for a statin and the 83% rate for a beta-blocker and 82% for an ACE inhibitor or an ARB could possibly be increased, although these percentages may reflect intolerance or contraindications to medications.

Clearly, ongoing review of STEMI care is important in guiding practice. The New Zealand ASC audits have given the ability to explore longitudinal comparisons of ACS care over time. As a result of these audits which produced a momentum for change, and the subsequent understanding by the Ministry of Health of the importance of ongoing audit of ACS medical practice, ANZACS-QI has been designed and implemented since 2013 and is funded by the Ministry of Health.17 This enables real time reporting of demographics, management and outcomes of STEMI patients and provides the opportunity to improve patient care.

Study limitations

This study has some limitations. It was an observational study with modest power given the study size. Despite this, these audits document an important evolution of the management of STEMI among consecutive, unselected patients in New Zealand over a decade. Details and timing of PCI were not available from earlier audits for comparison. We relied on local co-investigators to report relevant data which was not centrally verified. It is also to be noted that the investigators were aware that an audit was occurring, and it is unknown as to how this might have affected rates of prescribing evidence-based therapies and intervention rates.

Conclusion

Data collected in the 2002 Audit provided the momentum for change in resourcing and treatment of ACS in New Zealand. This paper confirms that there have been significant improvements in the management of STEMI patients in two subsequent audits over the last decade in terms of invasive management, investigations and medical therapy before and after discharge. Our study also highlights the importance of ongoing audit of the care of STEMI patients within the ongoing Ministry of Health-funded ANZACS-QI database. There is still room for improvement.

Appendix 1

Abbreviations/definitions

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