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Thrombolysis with intravenous alteplase within 4.5 hours after ischaemic stroke onset improves outcomes, with greater benefits seen with earlier treatment.1 The short therapeutic window means that a minority of ischaemic stroke patients are treated.2 The National Stroke Network introduced the National Stroke Thrombolysis Register as a quality improvement initiative on January 1, 2015. All stroke thrombolysis patients are entered into the register with regular reports to clinical and managerial staff at individual DHBs, the four regional stroke networks and at the annual Stroke Thrombolysis Data and Quality meetings. National targets for thrombolysis rates and treatment delays have been set with the aim to support clinicians driving improvements in hospital processes and thrombolysis rates. This has been the experience in other countries where large stroke registries and quality improvement efforts have enhanced stroke thrombolysis delivery.3

The first six months of the register showed a national thrombolysis rate of 6.4% against a target of 6%.2 This is lower than rates seen elsewhere, which range from 7% in Australia up to 11% in the UK in 2015.4–6 In-hospital treatment delays were identified as an area for improvement.2 We report trends in thrombolysis rates, treatment delays and short-term outcomes over the first 18 months of the register. The aim was to determine if there have been improvements in treatment rates, delays and short-term outcomes.

Methods

Data from consecutive ischaemic stroke patients treated with intravenous alteplase from January 1, 2015 to June 30, 2016 were prospectively entered into the National Stroke Thrombolysis Register. Information recorded included demographic data, treatment-related times (stroke onset, hospital arrival, computed tomography (CT) scanning and alteplase bolus) and complications of thrombolysis, including symptomatic intracranial haemorrhage (sICH). Symptomatic ICH was defined as local or remote parenchymal haematoma (PH) type II on the post-treatment CT scan, combined with neurologic deterioration of four points or greater on the National Institute of Health Stroke Scale (NIHSS) within 24 hours of treatment.7 Survival at day seven was the major outcome measure. The databases were maintained by stroke nurses and physicians. Data from each hospital was then de-identified and submitted to a central co-ordinator on a quarterly basis.

Stroke thrombolysis rates were calculated using the number of ‘ischaemic strokes’ and ‘strokes unspecified’ as denominators, in accordance with Ministry of Health thrombolysis indicator reporting guidelines. Large district health boards (DHBs) were defined as those with a catchment population of more than 250,000 (seven DHBs) people, medium-sized DHBs 125,000–250,000 (six) and small as less than 125,000 (seven). The 20 DHBs are arranged into four regional stroke networks; the Northern Regional Alliance (Northland, Waitemata, Auckland and Counties-Manukau DHBs); the Midland Region (Waikato, Bay of Plenty, Lakes, Tairawhiti and Taranaki); the Central Region (Hawke’s Bay, MidCentral, Whanganui, Hutt Valley, Wairarapa and Capital and Coast) and the South Island Alliance (Nelson-Marlborough, Canterbury, West Coast, South Canterbury and Southern).

Statistical analyses were performed using Microsoft Excel XLSTAT version 2016.4. The Chi square test was used for categorical outcomes. Quarterly differences were analysed with the Mann-Whitney U test for comparison of two groups and the Kruskal-Wallis test for three or more groups. A test was considered statistically significant with a p-value of less than 0.05.

Results

There were 623 stroke patients [mean (SD) age 70 (15) years, 29% aged ≥80 years, 55% male] treated with intravenous alteplase over the 18 months from January 1, 2015 to June 30, 2016 (Table 1). Of these patients, 71% were European, 15% Māori, 5% Pacific, 5% Asian and 4% Other. Over the same time period, there were 8,857 patients admitted to New Zealand hospitals and coded as ischaemic stroke or stroke unspecified, giving a national stroke thrombolysis rate of 7.0%. Patients were more likely to be thrombolysed in the second than the first nine months of the audit [350 of 4,456 (7.9%) patients versus 273 of 4,401 (6.8%); Chi squared=9.00, p=0.001, respectively]. Half of the patients (50%) were admitted during working hours, defined as 0800–1700 hours, Monday to Fridays (not including holidays) and 27% on weekends or holidays. Twenty-seven patients (4.3%) had stroke while already in-hospital.

There was incomplete time data in 26 (4.2%) of the 623 patients, who were excluded from analysis of some of the treatment delay measures (Table 1). The median (IQR) door-to-needle time reduced over the 18 months of the audit, from 77 (55–105) minutes in January–March 2015, to 64 (49–89) minutes in April–June 2016 (p=0.002). Patients were more likely to be treated within 60 minutes of hospital arrival in the second than the first nine months of the audit [137 of 325 (42%) patients versus 71 of 250, 28%; Chi squared=10.99, p=0.001, respectively]. There was a non-significant reduction in the stroke onset-to-treatment time, shortening from 162 (120–200) minutes to 140 (115–199) minutes (p=0.070). There were no changes in the onset-to-arrival or door-to-CT times between quarters over the study period.

Table 1: Demographics, timing and outcomes of stroke patients treated with intravenous alteplase from January 1, 2015 to June 30, 2016.

* The denominator used was the number of patients coded as ischaemic or stroke unspecified.

Four DHBs thrombolysed more than 65 patients, three DHBs between 40–65, eight DHBs between 10–39 and five small DHBs between 1–9 patients over the 18 months. The seven large DHBs thrombolysed most (416 of 623, 67%) patients (Table 2), with Capital and Coast DHB achieving a thrombolysis rate of 19.6% in one quarter of the audit. Thrombolysis rates increased with size of DHB from 59 of 1,056 (5.6%) patients in small DHBs, to 148 of 2,258 (6.6%) in medium DHBs and 416 of 5,543 patients (7.5%) in large DHBs (Chi squared=6.055, p=0.048). The Northern region thrombolysed the greatest number of patients (194), followed by the Central (161), Midland (140) and South Island (128) regions (Table 3). Thrombolysis rates were highest at 9.5% in the Central region, which also had the shortest median door-to-needle time (64 minutes) and treated the greatest proportion of patients (44%) within 60 minutes of hospital arrival.

Table 2: Treatment delays by DHB size from January 1, 2015 to June 30, 2016.

* The denominator used was the number of patients coded as ischaemic or stroke unspecified.
** Large DHBs (n=7) population >250,000 people
     Medium-sized DHBs (n=6) population 125,000–250,000 people
     Small DHBs (n=7) population <125,000 people.

The increasing treatment rates did not result in any increase in complications or mortality over the six quarters (Table 1). Rates of sICH, the most feared complication of stroke thrombolysis, remained stable over the audit (Chi squared=2.846, p=0.724), and was reported in 27 (4.3%) patients, of whom eight (30%) had died by day seven compared with 5.7% deaths in the 596 patients without sICH. Other complications of stroke thrombolysis included extra-cranial haemorrhage in nine (1.4%) and angioedema in two (0.3%) patients. Tenecteplase was given in error to two stroke patients, with sICH in one, both of whom were alive at day seven. Survival at day seven remained stable over the audit (Chi squared=4.177, p=0.524), and was reported in 93% patients.

Table 3: Treatment delays by regional network from January 1, 2015 to June 30, 2016.

* The denominator used was the number of patients coded as ischaemic or stroke unspecified.

Discussion

This audit has shown that the numbers of people treated with intravenous alteplase has increased over the 18 months of the register. Compared with earlier New Zealand studies, stroke thrombolysis rates nearly tripled from 3% in 2009,8 to 6.4% in mid-2015,9 and 8.4% by mid-2016. The efficiency of in-hospital processes have also improved with reductions in median door-to-needle time of 13 minutes and onset-to-needle time of 22 minutes. The increased thrombolysis rates have not come at the cost of increased sICH or short-term mortality. While this audit was not designed to determine whether the register and the targets set by the National Stroke Network have driven these improvements, it seems reasonable to assume that they have at least played a part.

There is room for improvement. Thrombolysis rates varied from 2–20% between different DHBs. Patients were more likely to be thrombolysed if they presented to large urban DHBs. The DHB with the highest thrombolysis rates was in a small densely populated urban location, while many of those with lower rates were in large sparsely populated regions. For centres without 24-hour local stroke specialist access, Telestroke, where patients are managed by stroke specialists via video-link, has the potential to increase thrombolysis rates. This has been confirmed in the yet to be published 2016 Central Region Telestroke pilot, where an interim evaluation found that out-of-hours thrombolysis rates increased from 7% to 20% (personal communication Dr Annemarei Ranta). There is also potential to increase out-of-hours thrombolysis rates through ambulance bypass to a single afterhours thrombolysis centre, which is currently being considered in the Northern Region.

It is important that DHBs and regional stroke networks work towards reducing stroke onset to thrombolysis treatment times. The sooner alteplase can be administered, the greater the chance of a patient having an improved outcome. Every 10-minute delay in starting alteplase results in one less patient with improved outcome for every 100 patients treated.10,11 Treatment delays can be broadly divided into those which occur before and after hospital arrival. Approximately half of the onset-to-treatment time delays occurred in the pre-hospital phase. The median door-to-needle time of 64 minutes compares favourably with 65–75 minutes reported in large international registries.12,13 However, the register showed that only 43% of patients were thrombolysed within a door-to-needle time of 60 minutes, which is lower than the Brain Attack Coalition target of treating at least 80% of patients within this timeframe.14

Multiple community and organisational changes can shorten treatment delays.15 The nationwide Face Arm Speech Time (FAST) media campaign launched in June 2016 aimed to raise public stroke awareness and reduce hospital presentation times. It is crucial that DHBs and regional stroke networks work in a coordinated way with ambulance services to reduce treatment times. This includes staff education programs and pre-notification via a ‘Code Stroke’ contact system (currently in place in 13 DHBs), where ambulance staff alert a rapid response stroke team about potential thrombolysis candidates. Patients can be met at the door, quickly assessed and directly transferred to the CT scanner where thrombolysis candidates should be given imaging priority. Stroke thrombolysis kits can be kept in the emergency department so that alteplase can be made up and the bolus delivered as soon as intracranial haemorrhage has been excluded. Such measures can result in alteplase treatment starting 22–28 minutes sooner.3,16

The increased numbers of stroke patients thrombolysed, and the reductions in treatment delays, have not resulted in an increase in complications through rushed assessments. Rates of sICH, day seven mortality and other complications were stable over the register period. However, it is of concern that two patients were treated with tenecteplase. Safety campaigns have since been instituted to mitigate such risks, including clinician education, the use of designated stroke thrombolysis kits and an advocacy for supervision from senior medical officers (SMOs).

The register has a number of limitations. We were reliant on the individuals completing the database for its accuracy, with no resources available to support the external review of the thrombolysed patients. We cannot exclude the possibility that increasing thrombolysis rates are due to greater compliance with the register. However, while the register has only been in place since 2015, DHBs have been reporting thrombolysis rates to the Ministry of Health since 2011, so there is some familiarity with this type of reporting. It is possible that complications such as sICH have been under-reported. sICH also requires a degree of expertise in interpreting clinical and imaging data, and there may have been inconsistencies in how definitions were applied. These issues are addressed in regional stroke update days and the national thrombolysis database meetings. A functional scale such as the modified Rankin Scale at three months would be a better measure of outcome than survival at day seven. However, the database is completed by clinicians in 20 very different DHBs, and a decision was made to keep the information recorded as simple as possible, and achievable within currently available clinical resources. The reasons for any DHB or regional variations have not been determined in a systematic way. These are issues that can be explored as the database develops over time.

The National Stroke Network set a target thrombolysis rate for individual DHBs of 6%. The target was exceeded nationally with those with higher thrombolysis rates making up for those with lower rates. The target was not meant to be aspirational but was set to be achievable by the majority of DHBs. The aim was to encourage improved thrombolysis rates over time, bearing in mind that rates of 20% have been achieved nationally and internationally. The Network is continuing to adjust key performance indicators, and stroke thrombolysis targets for individual DHBs have been increased to 8% for 2017 and 10% for 2018.

Summary

Abstract

Aim

To describe trends in treatment delays and short-term outcome over the first 18 months of the New Zealand stroke thrombolysis register.

Method

The National Stroke Network introduced a central register of all ischaemic stroke patients treated with intravenous alteplase on January 1, 2015. The aim was to increase thrombolysis treatment rates and drive improvements in safety.

Results

From January 1, 2015 to June 30, 2016, alteplase was given to 623 patients [344 men, mean (range) age 70 (22-98) years] out of a total of 8,857 ischaemic and unspecified stroke patients, giving a thrombolysis rate of 7.0%. Between the first and second halves of the audit, there were more patients thrombolysed [350 of 4,456 (7.9%) versus 273 of 4,401 (6.8%); p=0.001] and more treated within 60 minutes of hospital arrival [137 of 325 (42%) versus 71 of 250 (28%), p=0.001]. Door-to-needle time reduced from 77 minutes to 64 minutes (p=0.002) and the onset-to-treatment reduced from 162 minutes to 140 minutes (p=0.070). Rates of symptomatic intracranial haemorrhage (4.3% patients) and survival at day seven (93%) were stable.

Conclusion

There have been improvements in stroke thrombolysis rates and treatment delays in New Zealand hospitals since the institution of the National Stroke Network thrombolysis register. The Network will continue to adjust key performance indicators, and stroke thrombolysis targets for individual DHBs have been increased to 8% for 2017 and 10% for 2018.

Author Information

Qiliang Liu, Trainee Intern, Department of Neurology, Auckland City Hospital and University of Auckland; Annemarei (Anna) Ranta, Neurologist and National Clinical Leader Stroke, Department of Neurology, Wellington Regional Hospital and University of Otago; Ginny Abernethy, National Stroke Network Coordinator, Stroke Foundation of New Zealand; P Alan Barber, Professor, Neurologist and Director of the Auckland Hospital Stroke Service, Department of Neurology, Auckland City Hospital and University of Auckland, Auckland.

Acknowledgements

Correspondence

Professor Alan Barber, Neurology Department, Auckland City Hospital, Park Road, Grafton Auckland.

Correspondence Email

a.barber@auckland.ac.nz

Competing Interests

Nil.

  1. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. The New England Journal of Medicine 2008; 359(13):1317–29. doi: 10.1056/NEJMoa0804656
  2. Joshi P, Fink J, Barber PA, et al. Stroke thrombolysis in New Zealand: data from the first 6 months of the New Zealand Thrombolysis Register. The New Zealand Medical Journal 2016; 129(1438):44–9.
  3. Bray BD, Campbell J, Cloud GC, et al. Bigger, faster? Associations between hospital thrombolysis volume and speed of thrombolysis administration in acute ischemic stroke. Stroke; a journal of cerebral circulation 2013; 44(11):3129–35. doi: 10.1161/strokeaha.113.001981
  4. Levi C LR, Smith B, Blandin C, Parson M, Read S. The implementation of intravenous tissue plasminogen activator in acute ischemic stroke - a scientific position statement from the National Stroke Foundation and the Stroke Society of Australasia. Internal Medicine Journal 2009; 39:317–24.
  5. Australian National Stroke Foundation. National Stroke Audit – Acute Services Clinical Audit Report. Melbourne, Australia 2013
  6. Royal College of Physicians Sentinel Stroke National Audit Programme (SSNAP). Clinical audit April–June 2015 report prepared by Royal College of Physicians, Clinical Effectiveness and Evaluation Unit on behalf of the Intercollegiate Stroke Working Party. 2015.
  7. Wahlgren N, Ahmed N, Davalos A, et al. Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet, 2007; 369(9558):275–82. doi: 10.1016/s0140-6736(07)60149-4
  8. Fang MC, Cutler DM, Rosen AB. Trends in thrombolytic use for ischemic stroke in the United States. Journal of hospital medicine 2010; 5(7):406–9. doi: 10.1002/jhm.689
  9. New Zealand Stroke Foundation. National Acute Stroke Services Audit 2009. Wellington, New Zealand: Stroke Foundation of New Zealand 2010
  10. Ebinger M, Kunz A, Wendt M, et al. Effects of golden hour thrombolysis: a Prehospital Acute Neurological Treatment and Optimization of Medical Care in Stroke (PHANTOM-S) substudy. JAMA Neurology 2015; 72(1):25–30. doi: 10.1001/jamaneurol.2014.3188
  11. Saver JL, Fonarow GC, Smith EE, et al. Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke. JAMA 2013; 309(23):2480–8. doi: 10.1001/jama.2013.6959
  12. Kaye P, Shaw L, Madigan B, et al. Emergency department-focused thrombolysis for acute ischaemic stroke. Emergency medicine journal : EMJ 2011;28(2):102-6. doi: 10.1136/emj.2009.088096 [published Online First: 2010/08/21].
  13. Kleindorfer D, Xu Y, Moomaw CJ, et al. US geographic distribution of rt-PA utilization by hospital for acute ischemic stroke. Stroke; a journal of cerebral circulation 2009;40(11):3580-4. doi: 10.1161/strokeaha.109.554626 [published Online First: 2009/10/03].
  14. New Zealand Stroke Foundation. New Zealand Clinical Guidelines for Stroke Management. 2010
  15. Meretoja A, Strbian D, Mustanoja S, et al. Reducing in-hospital delay to 20 minutes in stroke thrombolysis. Neurology 2012;79(4):306-13. doi: 10.1212/WNL.0b013e31825d6011 [published Online First: 2012/05/25].
  16. Meretoja A, Weir L, Ugalde M, et al. Helsinki model cut stroke thrombolysis delays to 25 minutes in Melbourne in only 4 months. Neurology 2013; 81(12):1071–6. doi: 10.1212/WNL.0b013e3182a4a4d2 [published Online First: 2013/08/16].

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Thrombolysis with intravenous alteplase within 4.5 hours after ischaemic stroke onset improves outcomes, with greater benefits seen with earlier treatment.1 The short therapeutic window means that a minority of ischaemic stroke patients are treated.2 The National Stroke Network introduced the National Stroke Thrombolysis Register as a quality improvement initiative on January 1, 2015. All stroke thrombolysis patients are entered into the register with regular reports to clinical and managerial staff at individual DHBs, the four regional stroke networks and at the annual Stroke Thrombolysis Data and Quality meetings. National targets for thrombolysis rates and treatment delays have been set with the aim to support clinicians driving improvements in hospital processes and thrombolysis rates. This has been the experience in other countries where large stroke registries and quality improvement efforts have enhanced stroke thrombolysis delivery.3

The first six months of the register showed a national thrombolysis rate of 6.4% against a target of 6%.2 This is lower than rates seen elsewhere, which range from 7% in Australia up to 11% in the UK in 2015.4–6 In-hospital treatment delays were identified as an area for improvement.2 We report trends in thrombolysis rates, treatment delays and short-term outcomes over the first 18 months of the register. The aim was to determine if there have been improvements in treatment rates, delays and short-term outcomes.

Methods

Data from consecutive ischaemic stroke patients treated with intravenous alteplase from January 1, 2015 to June 30, 2016 were prospectively entered into the National Stroke Thrombolysis Register. Information recorded included demographic data, treatment-related times (stroke onset, hospital arrival, computed tomography (CT) scanning and alteplase bolus) and complications of thrombolysis, including symptomatic intracranial haemorrhage (sICH). Symptomatic ICH was defined as local or remote parenchymal haematoma (PH) type II on the post-treatment CT scan, combined with neurologic deterioration of four points or greater on the National Institute of Health Stroke Scale (NIHSS) within 24 hours of treatment.7 Survival at day seven was the major outcome measure. The databases were maintained by stroke nurses and physicians. Data from each hospital was then de-identified and submitted to a central co-ordinator on a quarterly basis.

Stroke thrombolysis rates were calculated using the number of ‘ischaemic strokes’ and ‘strokes unspecified’ as denominators, in accordance with Ministry of Health thrombolysis indicator reporting guidelines. Large district health boards (DHBs) were defined as those with a catchment population of more than 250,000 (seven DHBs) people, medium-sized DHBs 125,000–250,000 (six) and small as less than 125,000 (seven). The 20 DHBs are arranged into four regional stroke networks; the Northern Regional Alliance (Northland, Waitemata, Auckland and Counties-Manukau DHBs); the Midland Region (Waikato, Bay of Plenty, Lakes, Tairawhiti and Taranaki); the Central Region (Hawke’s Bay, MidCentral, Whanganui, Hutt Valley, Wairarapa and Capital and Coast) and the South Island Alliance (Nelson-Marlborough, Canterbury, West Coast, South Canterbury and Southern).

Statistical analyses were performed using Microsoft Excel XLSTAT version 2016.4. The Chi square test was used for categorical outcomes. Quarterly differences were analysed with the Mann-Whitney U test for comparison of two groups and the Kruskal-Wallis test for three or more groups. A test was considered statistically significant with a p-value of less than 0.05.

Results

There were 623 stroke patients [mean (SD) age 70 (15) years, 29% aged ≥80 years, 55% male] treated with intravenous alteplase over the 18 months from January 1, 2015 to June 30, 2016 (Table 1). Of these patients, 71% were European, 15% Māori, 5% Pacific, 5% Asian and 4% Other. Over the same time period, there were 8,857 patients admitted to New Zealand hospitals and coded as ischaemic stroke or stroke unspecified, giving a national stroke thrombolysis rate of 7.0%. Patients were more likely to be thrombolysed in the second than the first nine months of the audit [350 of 4,456 (7.9%) patients versus 273 of 4,401 (6.8%); Chi squared=9.00, p=0.001, respectively]. Half of the patients (50%) were admitted during working hours, defined as 0800–1700 hours, Monday to Fridays (not including holidays) and 27% on weekends or holidays. Twenty-seven patients (4.3%) had stroke while already in-hospital.

There was incomplete time data in 26 (4.2%) of the 623 patients, who were excluded from analysis of some of the treatment delay measures (Table 1). The median (IQR) door-to-needle time reduced over the 18 months of the audit, from 77 (55–105) minutes in January–March 2015, to 64 (49–89) minutes in April–June 2016 (p=0.002). Patients were more likely to be treated within 60 minutes of hospital arrival in the second than the first nine months of the audit [137 of 325 (42%) patients versus 71 of 250, 28%; Chi squared=10.99, p=0.001, respectively]. There was a non-significant reduction in the stroke onset-to-treatment time, shortening from 162 (120–200) minutes to 140 (115–199) minutes (p=0.070). There were no changes in the onset-to-arrival or door-to-CT times between quarters over the study period.

Table 1: Demographics, timing and outcomes of stroke patients treated with intravenous alteplase from January 1, 2015 to June 30, 2016.

* The denominator used was the number of patients coded as ischaemic or stroke unspecified.

Four DHBs thrombolysed more than 65 patients, three DHBs between 40–65, eight DHBs between 10–39 and five small DHBs between 1–9 patients over the 18 months. The seven large DHBs thrombolysed most (416 of 623, 67%) patients (Table 2), with Capital and Coast DHB achieving a thrombolysis rate of 19.6% in one quarter of the audit. Thrombolysis rates increased with size of DHB from 59 of 1,056 (5.6%) patients in small DHBs, to 148 of 2,258 (6.6%) in medium DHBs and 416 of 5,543 patients (7.5%) in large DHBs (Chi squared=6.055, p=0.048). The Northern region thrombolysed the greatest number of patients (194), followed by the Central (161), Midland (140) and South Island (128) regions (Table 3). Thrombolysis rates were highest at 9.5% in the Central region, which also had the shortest median door-to-needle time (64 minutes) and treated the greatest proportion of patients (44%) within 60 minutes of hospital arrival.

Table 2: Treatment delays by DHB size from January 1, 2015 to June 30, 2016.

* The denominator used was the number of patients coded as ischaemic or stroke unspecified.
** Large DHBs (n=7) population >250,000 people
     Medium-sized DHBs (n=6) population 125,000–250,000 people
     Small DHBs (n=7) population <125,000 people.

The increasing treatment rates did not result in any increase in complications or mortality over the six quarters (Table 1). Rates of sICH, the most feared complication of stroke thrombolysis, remained stable over the audit (Chi squared=2.846, p=0.724), and was reported in 27 (4.3%) patients, of whom eight (30%) had died by day seven compared with 5.7% deaths in the 596 patients without sICH. Other complications of stroke thrombolysis included extra-cranial haemorrhage in nine (1.4%) and angioedema in two (0.3%) patients. Tenecteplase was given in error to two stroke patients, with sICH in one, both of whom were alive at day seven. Survival at day seven remained stable over the audit (Chi squared=4.177, p=0.524), and was reported in 93% patients.

Table 3: Treatment delays by regional network from January 1, 2015 to June 30, 2016.

* The denominator used was the number of patients coded as ischaemic or stroke unspecified.

Discussion

This audit has shown that the numbers of people treated with intravenous alteplase has increased over the 18 months of the register. Compared with earlier New Zealand studies, stroke thrombolysis rates nearly tripled from 3% in 2009,8 to 6.4% in mid-2015,9 and 8.4% by mid-2016. The efficiency of in-hospital processes have also improved with reductions in median door-to-needle time of 13 minutes and onset-to-needle time of 22 minutes. The increased thrombolysis rates have not come at the cost of increased sICH or short-term mortality. While this audit was not designed to determine whether the register and the targets set by the National Stroke Network have driven these improvements, it seems reasonable to assume that they have at least played a part.

There is room for improvement. Thrombolysis rates varied from 2–20% between different DHBs. Patients were more likely to be thrombolysed if they presented to large urban DHBs. The DHB with the highest thrombolysis rates was in a small densely populated urban location, while many of those with lower rates were in large sparsely populated regions. For centres without 24-hour local stroke specialist access, Telestroke, where patients are managed by stroke specialists via video-link, has the potential to increase thrombolysis rates. This has been confirmed in the yet to be published 2016 Central Region Telestroke pilot, where an interim evaluation found that out-of-hours thrombolysis rates increased from 7% to 20% (personal communication Dr Annemarei Ranta). There is also potential to increase out-of-hours thrombolysis rates through ambulance bypass to a single afterhours thrombolysis centre, which is currently being considered in the Northern Region.

It is important that DHBs and regional stroke networks work towards reducing stroke onset to thrombolysis treatment times. The sooner alteplase can be administered, the greater the chance of a patient having an improved outcome. Every 10-minute delay in starting alteplase results in one less patient with improved outcome for every 100 patients treated.10,11 Treatment delays can be broadly divided into those which occur before and after hospital arrival. Approximately half of the onset-to-treatment time delays occurred in the pre-hospital phase. The median door-to-needle time of 64 minutes compares favourably with 65–75 minutes reported in large international registries.12,13 However, the register showed that only 43% of patients were thrombolysed within a door-to-needle time of 60 minutes, which is lower than the Brain Attack Coalition target of treating at least 80% of patients within this timeframe.14

Multiple community and organisational changes can shorten treatment delays.15 The nationwide Face Arm Speech Time (FAST) media campaign launched in June 2016 aimed to raise public stroke awareness and reduce hospital presentation times. It is crucial that DHBs and regional stroke networks work in a coordinated way with ambulance services to reduce treatment times. This includes staff education programs and pre-notification via a ‘Code Stroke’ contact system (currently in place in 13 DHBs), where ambulance staff alert a rapid response stroke team about potential thrombolysis candidates. Patients can be met at the door, quickly assessed and directly transferred to the CT scanner where thrombolysis candidates should be given imaging priority. Stroke thrombolysis kits can be kept in the emergency department so that alteplase can be made up and the bolus delivered as soon as intracranial haemorrhage has been excluded. Such measures can result in alteplase treatment starting 22–28 minutes sooner.3,16

The increased numbers of stroke patients thrombolysed, and the reductions in treatment delays, have not resulted in an increase in complications through rushed assessments. Rates of sICH, day seven mortality and other complications were stable over the register period. However, it is of concern that two patients were treated with tenecteplase. Safety campaigns have since been instituted to mitigate such risks, including clinician education, the use of designated stroke thrombolysis kits and an advocacy for supervision from senior medical officers (SMOs).

The register has a number of limitations. We were reliant on the individuals completing the database for its accuracy, with no resources available to support the external review of the thrombolysed patients. We cannot exclude the possibility that increasing thrombolysis rates are due to greater compliance with the register. However, while the register has only been in place since 2015, DHBs have been reporting thrombolysis rates to the Ministry of Health since 2011, so there is some familiarity with this type of reporting. It is possible that complications such as sICH have been under-reported. sICH also requires a degree of expertise in interpreting clinical and imaging data, and there may have been inconsistencies in how definitions were applied. These issues are addressed in regional stroke update days and the national thrombolysis database meetings. A functional scale such as the modified Rankin Scale at three months would be a better measure of outcome than survival at day seven. However, the database is completed by clinicians in 20 very different DHBs, and a decision was made to keep the information recorded as simple as possible, and achievable within currently available clinical resources. The reasons for any DHB or regional variations have not been determined in a systematic way. These are issues that can be explored as the database develops over time.

The National Stroke Network set a target thrombolysis rate for individual DHBs of 6%. The target was exceeded nationally with those with higher thrombolysis rates making up for those with lower rates. The target was not meant to be aspirational but was set to be achievable by the majority of DHBs. The aim was to encourage improved thrombolysis rates over time, bearing in mind that rates of 20% have been achieved nationally and internationally. The Network is continuing to adjust key performance indicators, and stroke thrombolysis targets for individual DHBs have been increased to 8% for 2017 and 10% for 2018.

Summary

Abstract

Aim

To describe trends in treatment delays and short-term outcome over the first 18 months of the New Zealand stroke thrombolysis register.

Method

The National Stroke Network introduced a central register of all ischaemic stroke patients treated with intravenous alteplase on January 1, 2015. The aim was to increase thrombolysis treatment rates and drive improvements in safety.

Results

From January 1, 2015 to June 30, 2016, alteplase was given to 623 patients [344 men, mean (range) age 70 (22-98) years] out of a total of 8,857 ischaemic and unspecified stroke patients, giving a thrombolysis rate of 7.0%. Between the first and second halves of the audit, there were more patients thrombolysed [350 of 4,456 (7.9%) versus 273 of 4,401 (6.8%); p=0.001] and more treated within 60 minutes of hospital arrival [137 of 325 (42%) versus 71 of 250 (28%), p=0.001]. Door-to-needle time reduced from 77 minutes to 64 minutes (p=0.002) and the onset-to-treatment reduced from 162 minutes to 140 minutes (p=0.070). Rates of symptomatic intracranial haemorrhage (4.3% patients) and survival at day seven (93%) were stable.

Conclusion

There have been improvements in stroke thrombolysis rates and treatment delays in New Zealand hospitals since the institution of the National Stroke Network thrombolysis register. The Network will continue to adjust key performance indicators, and stroke thrombolysis targets for individual DHBs have been increased to 8% for 2017 and 10% for 2018.

Author Information

Qiliang Liu, Trainee Intern, Department of Neurology, Auckland City Hospital and University of Auckland; Annemarei (Anna) Ranta, Neurologist and National Clinical Leader Stroke, Department of Neurology, Wellington Regional Hospital and University of Otago; Ginny Abernethy, National Stroke Network Coordinator, Stroke Foundation of New Zealand; P Alan Barber, Professor, Neurologist and Director of the Auckland Hospital Stroke Service, Department of Neurology, Auckland City Hospital and University of Auckland, Auckland.

Acknowledgements

Correspondence

Professor Alan Barber, Neurology Department, Auckland City Hospital, Park Road, Grafton Auckland.

Correspondence Email

a.barber@auckland.ac.nz

Competing Interests

Nil.

  1. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. The New England Journal of Medicine 2008; 359(13):1317–29. doi: 10.1056/NEJMoa0804656
  2. Joshi P, Fink J, Barber PA, et al. Stroke thrombolysis in New Zealand: data from the first 6 months of the New Zealand Thrombolysis Register. The New Zealand Medical Journal 2016; 129(1438):44–9.
  3. Bray BD, Campbell J, Cloud GC, et al. Bigger, faster? Associations between hospital thrombolysis volume and speed of thrombolysis administration in acute ischemic stroke. Stroke; a journal of cerebral circulation 2013; 44(11):3129–35. doi: 10.1161/strokeaha.113.001981
  4. Levi C LR, Smith B, Blandin C, Parson M, Read S. The implementation of intravenous tissue plasminogen activator in acute ischemic stroke - a scientific position statement from the National Stroke Foundation and the Stroke Society of Australasia. Internal Medicine Journal 2009; 39:317–24.
  5. Australian National Stroke Foundation. National Stroke Audit – Acute Services Clinical Audit Report. Melbourne, Australia 2013
  6. Royal College of Physicians Sentinel Stroke National Audit Programme (SSNAP). Clinical audit April–June 2015 report prepared by Royal College of Physicians, Clinical Effectiveness and Evaluation Unit on behalf of the Intercollegiate Stroke Working Party. 2015.
  7. Wahlgren N, Ahmed N, Davalos A, et al. Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet, 2007; 369(9558):275–82. doi: 10.1016/s0140-6736(07)60149-4
  8. Fang MC, Cutler DM, Rosen AB. Trends in thrombolytic use for ischemic stroke in the United States. Journal of hospital medicine 2010; 5(7):406–9. doi: 10.1002/jhm.689
  9. New Zealand Stroke Foundation. National Acute Stroke Services Audit 2009. Wellington, New Zealand: Stroke Foundation of New Zealand 2010
  10. Ebinger M, Kunz A, Wendt M, et al. Effects of golden hour thrombolysis: a Prehospital Acute Neurological Treatment and Optimization of Medical Care in Stroke (PHANTOM-S) substudy. JAMA Neurology 2015; 72(1):25–30. doi: 10.1001/jamaneurol.2014.3188
  11. Saver JL, Fonarow GC, Smith EE, et al. Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke. JAMA 2013; 309(23):2480–8. doi: 10.1001/jama.2013.6959
  12. Kaye P, Shaw L, Madigan B, et al. Emergency department-focused thrombolysis for acute ischaemic stroke. Emergency medicine journal : EMJ 2011;28(2):102-6. doi: 10.1136/emj.2009.088096 [published Online First: 2010/08/21].
  13. Kleindorfer D, Xu Y, Moomaw CJ, et al. US geographic distribution of rt-PA utilization by hospital for acute ischemic stroke. Stroke; a journal of cerebral circulation 2009;40(11):3580-4. doi: 10.1161/strokeaha.109.554626 [published Online First: 2009/10/03].
  14. New Zealand Stroke Foundation. New Zealand Clinical Guidelines for Stroke Management. 2010
  15. Meretoja A, Strbian D, Mustanoja S, et al. Reducing in-hospital delay to 20 minutes in stroke thrombolysis. Neurology 2012;79(4):306-13. doi: 10.1212/WNL.0b013e31825d6011 [published Online First: 2012/05/25].
  16. Meretoja A, Weir L, Ugalde M, et al. Helsinki model cut stroke thrombolysis delays to 25 minutes in Melbourne in only 4 months. Neurology 2013; 81(12):1071–6. doi: 10.1212/WNL.0b013e3182a4a4d2 [published Online First: 2013/08/16].

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Thrombolysis with intravenous alteplase within 4.5 hours after ischaemic stroke onset improves outcomes, with greater benefits seen with earlier treatment.1 The short therapeutic window means that a minority of ischaemic stroke patients are treated.2 The National Stroke Network introduced the National Stroke Thrombolysis Register as a quality improvement initiative on January 1, 2015. All stroke thrombolysis patients are entered into the register with regular reports to clinical and managerial staff at individual DHBs, the four regional stroke networks and at the annual Stroke Thrombolysis Data and Quality meetings. National targets for thrombolysis rates and treatment delays have been set with the aim to support clinicians driving improvements in hospital processes and thrombolysis rates. This has been the experience in other countries where large stroke registries and quality improvement efforts have enhanced stroke thrombolysis delivery.3

The first six months of the register showed a national thrombolysis rate of 6.4% against a target of 6%.2 This is lower than rates seen elsewhere, which range from 7% in Australia up to 11% in the UK in 2015.4–6 In-hospital treatment delays were identified as an area for improvement.2 We report trends in thrombolysis rates, treatment delays and short-term outcomes over the first 18 months of the register. The aim was to determine if there have been improvements in treatment rates, delays and short-term outcomes.

Methods

Data from consecutive ischaemic stroke patients treated with intravenous alteplase from January 1, 2015 to June 30, 2016 were prospectively entered into the National Stroke Thrombolysis Register. Information recorded included demographic data, treatment-related times (stroke onset, hospital arrival, computed tomography (CT) scanning and alteplase bolus) and complications of thrombolysis, including symptomatic intracranial haemorrhage (sICH). Symptomatic ICH was defined as local or remote parenchymal haematoma (PH) type II on the post-treatment CT scan, combined with neurologic deterioration of four points or greater on the National Institute of Health Stroke Scale (NIHSS) within 24 hours of treatment.7 Survival at day seven was the major outcome measure. The databases were maintained by stroke nurses and physicians. Data from each hospital was then de-identified and submitted to a central co-ordinator on a quarterly basis.

Stroke thrombolysis rates were calculated using the number of ‘ischaemic strokes’ and ‘strokes unspecified’ as denominators, in accordance with Ministry of Health thrombolysis indicator reporting guidelines. Large district health boards (DHBs) were defined as those with a catchment population of more than 250,000 (seven DHBs) people, medium-sized DHBs 125,000–250,000 (six) and small as less than 125,000 (seven). The 20 DHBs are arranged into four regional stroke networks; the Northern Regional Alliance (Northland, Waitemata, Auckland and Counties-Manukau DHBs); the Midland Region (Waikato, Bay of Plenty, Lakes, Tairawhiti and Taranaki); the Central Region (Hawke’s Bay, MidCentral, Whanganui, Hutt Valley, Wairarapa and Capital and Coast) and the South Island Alliance (Nelson-Marlborough, Canterbury, West Coast, South Canterbury and Southern).

Statistical analyses were performed using Microsoft Excel XLSTAT version 2016.4. The Chi square test was used for categorical outcomes. Quarterly differences were analysed with the Mann-Whitney U test for comparison of two groups and the Kruskal-Wallis test for three or more groups. A test was considered statistically significant with a p-value of less than 0.05.

Results

There were 623 stroke patients [mean (SD) age 70 (15) years, 29% aged ≥80 years, 55% male] treated with intravenous alteplase over the 18 months from January 1, 2015 to June 30, 2016 (Table 1). Of these patients, 71% were European, 15% Māori, 5% Pacific, 5% Asian and 4% Other. Over the same time period, there were 8,857 patients admitted to New Zealand hospitals and coded as ischaemic stroke or stroke unspecified, giving a national stroke thrombolysis rate of 7.0%. Patients were more likely to be thrombolysed in the second than the first nine months of the audit [350 of 4,456 (7.9%) patients versus 273 of 4,401 (6.8%); Chi squared=9.00, p=0.001, respectively]. Half of the patients (50%) were admitted during working hours, defined as 0800–1700 hours, Monday to Fridays (not including holidays) and 27% on weekends or holidays. Twenty-seven patients (4.3%) had stroke while already in-hospital.

There was incomplete time data in 26 (4.2%) of the 623 patients, who were excluded from analysis of some of the treatment delay measures (Table 1). The median (IQR) door-to-needle time reduced over the 18 months of the audit, from 77 (55–105) minutes in January–March 2015, to 64 (49–89) minutes in April–June 2016 (p=0.002). Patients were more likely to be treated within 60 minutes of hospital arrival in the second than the first nine months of the audit [137 of 325 (42%) patients versus 71 of 250, 28%; Chi squared=10.99, p=0.001, respectively]. There was a non-significant reduction in the stroke onset-to-treatment time, shortening from 162 (120–200) minutes to 140 (115–199) minutes (p=0.070). There were no changes in the onset-to-arrival or door-to-CT times between quarters over the study period.

Table 1: Demographics, timing and outcomes of stroke patients treated with intravenous alteplase from January 1, 2015 to June 30, 2016.

* The denominator used was the number of patients coded as ischaemic or stroke unspecified.

Four DHBs thrombolysed more than 65 patients, three DHBs between 40–65, eight DHBs between 10–39 and five small DHBs between 1–9 patients over the 18 months. The seven large DHBs thrombolysed most (416 of 623, 67%) patients (Table 2), with Capital and Coast DHB achieving a thrombolysis rate of 19.6% in one quarter of the audit. Thrombolysis rates increased with size of DHB from 59 of 1,056 (5.6%) patients in small DHBs, to 148 of 2,258 (6.6%) in medium DHBs and 416 of 5,543 patients (7.5%) in large DHBs (Chi squared=6.055, p=0.048). The Northern region thrombolysed the greatest number of patients (194), followed by the Central (161), Midland (140) and South Island (128) regions (Table 3). Thrombolysis rates were highest at 9.5% in the Central region, which also had the shortest median door-to-needle time (64 minutes) and treated the greatest proportion of patients (44%) within 60 minutes of hospital arrival.

Table 2: Treatment delays by DHB size from January 1, 2015 to June 30, 2016.

* The denominator used was the number of patients coded as ischaemic or stroke unspecified.
** Large DHBs (n=7) population >250,000 people
     Medium-sized DHBs (n=6) population 125,000–250,000 people
     Small DHBs (n=7) population <125,000 people.

The increasing treatment rates did not result in any increase in complications or mortality over the six quarters (Table 1). Rates of sICH, the most feared complication of stroke thrombolysis, remained stable over the audit (Chi squared=2.846, p=0.724), and was reported in 27 (4.3%) patients, of whom eight (30%) had died by day seven compared with 5.7% deaths in the 596 patients without sICH. Other complications of stroke thrombolysis included extra-cranial haemorrhage in nine (1.4%) and angioedema in two (0.3%) patients. Tenecteplase was given in error to two stroke patients, with sICH in one, both of whom were alive at day seven. Survival at day seven remained stable over the audit (Chi squared=4.177, p=0.524), and was reported in 93% patients.

Table 3: Treatment delays by regional network from January 1, 2015 to June 30, 2016.

* The denominator used was the number of patients coded as ischaemic or stroke unspecified.

Discussion

This audit has shown that the numbers of people treated with intravenous alteplase has increased over the 18 months of the register. Compared with earlier New Zealand studies, stroke thrombolysis rates nearly tripled from 3% in 2009,8 to 6.4% in mid-2015,9 and 8.4% by mid-2016. The efficiency of in-hospital processes have also improved with reductions in median door-to-needle time of 13 minutes and onset-to-needle time of 22 minutes. The increased thrombolysis rates have not come at the cost of increased sICH or short-term mortality. While this audit was not designed to determine whether the register and the targets set by the National Stroke Network have driven these improvements, it seems reasonable to assume that they have at least played a part.

There is room for improvement. Thrombolysis rates varied from 2–20% between different DHBs. Patients were more likely to be thrombolysed if they presented to large urban DHBs. The DHB with the highest thrombolysis rates was in a small densely populated urban location, while many of those with lower rates were in large sparsely populated regions. For centres without 24-hour local stroke specialist access, Telestroke, where patients are managed by stroke specialists via video-link, has the potential to increase thrombolysis rates. This has been confirmed in the yet to be published 2016 Central Region Telestroke pilot, where an interim evaluation found that out-of-hours thrombolysis rates increased from 7% to 20% (personal communication Dr Annemarei Ranta). There is also potential to increase out-of-hours thrombolysis rates through ambulance bypass to a single afterhours thrombolysis centre, which is currently being considered in the Northern Region.

It is important that DHBs and regional stroke networks work towards reducing stroke onset to thrombolysis treatment times. The sooner alteplase can be administered, the greater the chance of a patient having an improved outcome. Every 10-minute delay in starting alteplase results in one less patient with improved outcome for every 100 patients treated.10,11 Treatment delays can be broadly divided into those which occur before and after hospital arrival. Approximately half of the onset-to-treatment time delays occurred in the pre-hospital phase. The median door-to-needle time of 64 minutes compares favourably with 65–75 minutes reported in large international registries.12,13 However, the register showed that only 43% of patients were thrombolysed within a door-to-needle time of 60 minutes, which is lower than the Brain Attack Coalition target of treating at least 80% of patients within this timeframe.14

Multiple community and organisational changes can shorten treatment delays.15 The nationwide Face Arm Speech Time (FAST) media campaign launched in June 2016 aimed to raise public stroke awareness and reduce hospital presentation times. It is crucial that DHBs and regional stroke networks work in a coordinated way with ambulance services to reduce treatment times. This includes staff education programs and pre-notification via a ‘Code Stroke’ contact system (currently in place in 13 DHBs), where ambulance staff alert a rapid response stroke team about potential thrombolysis candidates. Patients can be met at the door, quickly assessed and directly transferred to the CT scanner where thrombolysis candidates should be given imaging priority. Stroke thrombolysis kits can be kept in the emergency department so that alteplase can be made up and the bolus delivered as soon as intracranial haemorrhage has been excluded. Such measures can result in alteplase treatment starting 22–28 minutes sooner.3,16

The increased numbers of stroke patients thrombolysed, and the reductions in treatment delays, have not resulted in an increase in complications through rushed assessments. Rates of sICH, day seven mortality and other complications were stable over the register period. However, it is of concern that two patients were treated with tenecteplase. Safety campaigns have since been instituted to mitigate such risks, including clinician education, the use of designated stroke thrombolysis kits and an advocacy for supervision from senior medical officers (SMOs).

The register has a number of limitations. We were reliant on the individuals completing the database for its accuracy, with no resources available to support the external review of the thrombolysed patients. We cannot exclude the possibility that increasing thrombolysis rates are due to greater compliance with the register. However, while the register has only been in place since 2015, DHBs have been reporting thrombolysis rates to the Ministry of Health since 2011, so there is some familiarity with this type of reporting. It is possible that complications such as sICH have been under-reported. sICH also requires a degree of expertise in interpreting clinical and imaging data, and there may have been inconsistencies in how definitions were applied. These issues are addressed in regional stroke update days and the national thrombolysis database meetings. A functional scale such as the modified Rankin Scale at three months would be a better measure of outcome than survival at day seven. However, the database is completed by clinicians in 20 very different DHBs, and a decision was made to keep the information recorded as simple as possible, and achievable within currently available clinical resources. The reasons for any DHB or regional variations have not been determined in a systematic way. These are issues that can be explored as the database develops over time.

The National Stroke Network set a target thrombolysis rate for individual DHBs of 6%. The target was exceeded nationally with those with higher thrombolysis rates making up for those with lower rates. The target was not meant to be aspirational but was set to be achievable by the majority of DHBs. The aim was to encourage improved thrombolysis rates over time, bearing in mind that rates of 20% have been achieved nationally and internationally. The Network is continuing to adjust key performance indicators, and stroke thrombolysis targets for individual DHBs have been increased to 8% for 2017 and 10% for 2018.

Summary

Abstract

Aim

To describe trends in treatment delays and short-term outcome over the first 18 months of the New Zealand stroke thrombolysis register.

Method

The National Stroke Network introduced a central register of all ischaemic stroke patients treated with intravenous alteplase on January 1, 2015. The aim was to increase thrombolysis treatment rates and drive improvements in safety.

Results

From January 1, 2015 to June 30, 2016, alteplase was given to 623 patients [344 men, mean (range) age 70 (22-98) years] out of a total of 8,857 ischaemic and unspecified stroke patients, giving a thrombolysis rate of 7.0%. Between the first and second halves of the audit, there were more patients thrombolysed [350 of 4,456 (7.9%) versus 273 of 4,401 (6.8%); p=0.001] and more treated within 60 minutes of hospital arrival [137 of 325 (42%) versus 71 of 250 (28%), p=0.001]. Door-to-needle time reduced from 77 minutes to 64 minutes (p=0.002) and the onset-to-treatment reduced from 162 minutes to 140 minutes (p=0.070). Rates of symptomatic intracranial haemorrhage (4.3% patients) and survival at day seven (93%) were stable.

Conclusion

There have been improvements in stroke thrombolysis rates and treatment delays in New Zealand hospitals since the institution of the National Stroke Network thrombolysis register. The Network will continue to adjust key performance indicators, and stroke thrombolysis targets for individual DHBs have been increased to 8% for 2017 and 10% for 2018.

Author Information

Qiliang Liu, Trainee Intern, Department of Neurology, Auckland City Hospital and University of Auckland; Annemarei (Anna) Ranta, Neurologist and National Clinical Leader Stroke, Department of Neurology, Wellington Regional Hospital and University of Otago; Ginny Abernethy, National Stroke Network Coordinator, Stroke Foundation of New Zealand; P Alan Barber, Professor, Neurologist and Director of the Auckland Hospital Stroke Service, Department of Neurology, Auckland City Hospital and University of Auckland, Auckland.

Acknowledgements

Correspondence

Professor Alan Barber, Neurology Department, Auckland City Hospital, Park Road, Grafton Auckland.

Correspondence Email

a.barber@auckland.ac.nz

Competing Interests

Nil.

  1. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. The New England Journal of Medicine 2008; 359(13):1317–29. doi: 10.1056/NEJMoa0804656
  2. Joshi P, Fink J, Barber PA, et al. Stroke thrombolysis in New Zealand: data from the first 6 months of the New Zealand Thrombolysis Register. The New Zealand Medical Journal 2016; 129(1438):44–9.
  3. Bray BD, Campbell J, Cloud GC, et al. Bigger, faster? Associations between hospital thrombolysis volume and speed of thrombolysis administration in acute ischemic stroke. Stroke; a journal of cerebral circulation 2013; 44(11):3129–35. doi: 10.1161/strokeaha.113.001981
  4. Levi C LR, Smith B, Blandin C, Parson M, Read S. The implementation of intravenous tissue plasminogen activator in acute ischemic stroke - a scientific position statement from the National Stroke Foundation and the Stroke Society of Australasia. Internal Medicine Journal 2009; 39:317–24.
  5. Australian National Stroke Foundation. National Stroke Audit – Acute Services Clinical Audit Report. Melbourne, Australia 2013
  6. Royal College of Physicians Sentinel Stroke National Audit Programme (SSNAP). Clinical audit April–June 2015 report prepared by Royal College of Physicians, Clinical Effectiveness and Evaluation Unit on behalf of the Intercollegiate Stroke Working Party. 2015.
  7. Wahlgren N, Ahmed N, Davalos A, et al. Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet, 2007; 369(9558):275–82. doi: 10.1016/s0140-6736(07)60149-4
  8. Fang MC, Cutler DM, Rosen AB. Trends in thrombolytic use for ischemic stroke in the United States. Journal of hospital medicine 2010; 5(7):406–9. doi: 10.1002/jhm.689
  9. New Zealand Stroke Foundation. National Acute Stroke Services Audit 2009. Wellington, New Zealand: Stroke Foundation of New Zealand 2010
  10. Ebinger M, Kunz A, Wendt M, et al. Effects of golden hour thrombolysis: a Prehospital Acute Neurological Treatment and Optimization of Medical Care in Stroke (PHANTOM-S) substudy. JAMA Neurology 2015; 72(1):25–30. doi: 10.1001/jamaneurol.2014.3188
  11. Saver JL, Fonarow GC, Smith EE, et al. Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke. JAMA 2013; 309(23):2480–8. doi: 10.1001/jama.2013.6959
  12. Kaye P, Shaw L, Madigan B, et al. Emergency department-focused thrombolysis for acute ischaemic stroke. Emergency medicine journal : EMJ 2011;28(2):102-6. doi: 10.1136/emj.2009.088096 [published Online First: 2010/08/21].
  13. Kleindorfer D, Xu Y, Moomaw CJ, et al. US geographic distribution of rt-PA utilization by hospital for acute ischemic stroke. Stroke; a journal of cerebral circulation 2009;40(11):3580-4. doi: 10.1161/strokeaha.109.554626 [published Online First: 2009/10/03].
  14. New Zealand Stroke Foundation. New Zealand Clinical Guidelines for Stroke Management. 2010
  15. Meretoja A, Strbian D, Mustanoja S, et al. Reducing in-hospital delay to 20 minutes in stroke thrombolysis. Neurology 2012;79(4):306-13. doi: 10.1212/WNL.0b013e31825d6011 [published Online First: 2012/05/25].
  16. Meretoja A, Weir L, Ugalde M, et al. Helsinki model cut stroke thrombolysis delays to 25 minutes in Melbourne in only 4 months. Neurology 2013; 81(12):1071–6. doi: 10.1212/WNL.0b013e3182a4a4d2 [published Online First: 2013/08/16].

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