Author + information
- Received May 12, 2011
- Accepted May 25, 2011
- Published online August 1, 2011.
- Thao Huynh, MD, MSc⁎,⁎ (, )
- John Birkhead, MB††,
- Kurt Huber, MD∥∥,
- Jennifer O'Loughlin, PhD†,
- Ulf Stenestrand, MD, PhD¶¶,
- Clive Weston, MD§§,
- Tomas Jernberg, MD, PhD##,
- Michael Schull, MD, MSc§,
- Robert C. Welsh, MD¶,
- Ali E. Denktas, MD⁎⁎⁎,
- Andrew Travers, MD⁎⁎,
- Sunil Sookram, MD#,
- Pierre Theroux, MD‡,
- Jack V. Tu, MD, PhD∥,
- Adams Timmis, MA, MD‡‡,
- Richard Smalling, MD, PhD⁎⁎⁎ and
- Nicolas Danchin, MD†††
- ↵⁎Reprint requests and correspondence
: Dr. Thao Huynh, McGill Health University Center, 1650 Avenue Cedar, Room E-5200, Montreal, Quebec H3G-1A4, Canada
Objectives The primary objective of this report was to describe the infrastructures and processes of selected European and North American pre-hospital fibrinolysis (PHL) programs. A secondary objective is to report the outcome data of the PHL programs surveyed.
Background Despite its benefit in reducing mortality in patients with ST-segment elevation myocardial infarction, PHL remained underused in North America. Examination of existing programs may provide insights to help address barriers to the implementation of PHL.
Methods The leading investigators of PHL research projects/national registries were invited to respond to a survey on the organization and outcomes of their affiliated PHL programs.
Results PHL was successfully deployed in a wide range of geographic territories (Europe: France, Sweden, Vienna, England, and Wales; North America: Houston, Edmonton, and Nova Scotia) and was delivered by healthcare professionals of varying expertise. In-hospital major adverse outcomes were rare with mortality of 3% to 6%, reinfarction of 2% to 5%, and stroke of <2%.
Conclusions Combining formal protocols for PHL for some patients with direct transportation of others to a percutaneous coronary intervention hospital for primary percutaneous coronary intervention would allow for tailored reperfusion therapy for patients with ST-segment elevation myocardial infarction. Insights from a variety of international settings may promote widespread use of PHL and increase timely coronary reperfusion worldwide.
Timely reperfusion through the administration of fibrinolytic therapy (FL) or primary percutaneous intervention (PCI) is critical in the management of acute myocardial infarction with ST-segment elevation (1,2). Compared with in-hospital administration, pre-hospital administration of FL (PHL) allows for earlier treatment and better survival rates (3). Whereas primary PCI is the preferred reperfusion therapy, PHL may be superior to primary PCI in reducing mortality among patients with ST-segment elevation myocardial infarction (STEMI) who present early (i.e., less than 2 h after the onset of symptoms) (4,5). For rural populations, PHL may be the only reperfusion strategy that can be provided in a timely manner (6).
PHL requires a complex pre-hospital system of care to enable prompt and accurate recognition of STEMI and skilled management of life-threatening complications of PHL such as arrhythmia, major bleeding, and stroke (6). Despite this complexity, PHL has been endorsed by the European Society of Cardiology (7–9) and has been well established in Europe for over 2 decades (7–9). In contrast, PHL is available in very few American and Canadian regions (10), despite the larger territories and high proportion of rural populations in these countries compared with Europe (10–12).
Insights on the infrastructures and processes that support PHL care in Europe and North America may assist other jurisdictions to implement PHL systems of care. Based on the longer European experience, patients who received PHL in these regions would be likely to have more favorable survival rates and fewer major complications than would patients treated by less-experienced PHL programs. Therefore, European PHL survival data may serve as an optimal benchmark for other PHL programs. The primary objective of this article was to describe the infrastructures and processes of selected European and North American PHL programs. The secondary objective was to report outcome data of the PHL programs surveyed.
Selection of PHL programs
We contacted cardiology experts in STEMI treatment to inquire about available PHL programs in Europe and North America. We obtained 100% response from the leading investigators of the 7 PHL programs contacted: England/Wales, France, Vienna, and Sweden from Europe; Edmonton and Nova Scotia from Canada; and Houston, Texas, from the United States.
Affiliated PHL research programs/national registries
All the participating PHL programs had affiliated research projects which were MINAP (Myocardial Ischemia National Audit Project) in England/Wales (13), FAST-MI (French Registry on Acute ST-Elevation Myocardial Infarction) in France (14), RIKS-HIA (Register of Information and Knowledge About Swedish Heart Intensive Care Admissions) in Sweden, Vienna-STEMI Registry in Vienna, AMICO (Alliance for Myocardial Infarction Care Optimization) in Houston, Vital Heart Response in Edmonton, and the Cardiovascular Health Nova Scotia Program in Nova Scotia.
PHL may have different impacts on STEMI morbidity and mortality depending on the rural-urban mix of the population served and access to hospitals that can deliver alternate reperfusion therapy such as primary PCI. Most recent data relevant to each PHL program included in this study on the territory and population served were extracted from the official Website of United Nation Statistics (available only for the year 2008) (15). We defined “rural” as all “nonurban” regions with a population of less than 1,000 persons, and a population density less than 400 persons per km2 (Organisation for Economic Co-operation and Development's definition) (16). For jurisdictions other than countries, we extracted population and geography data in 2008, from the national statistical Websites that is, for England and Wales (Office for National Statistics of England) (17), for Nova Scotia and Edmonton (Statistics Canada) (18), for Vienna (City of Vienna Information Center) (19), and Houston (United States Census Bureau) (20). Data on the number of hospitals, the proportion of hospitals with PCI facilities (PCI-hospital), and the annual incidence of STEMI within each jurisdiction were provided by the leading investigators of the PHL programs surveyed.
In August 2008, we mailed a self-administered questionnaire (Online Appendix 1) to the lead investigators of 7 participating PHL programs. The questionnaire collected data on pre-hospital services available, as well as information on the infrastructure of the PHL program and how the program worked (i.e., its processes). Questionnaires were completed in full by all the surveyed programs in April 2009. We recontacted respondents in June 2010 to inquire about recent modifications to the PHL programs.
The investigators were also asked to report the aggregate data since the initiation of the PHL program, as well as for the years 2005 to 2008. Outcomes data in these recent three years would be more clinically relevant than outcome data in the past decade because there were numerous recent innovations in the treatment of STEMI. Due to confidentiality issues, we could not obtain individual patient data from the PHL programs surveyed.
There was marked variation in the proportion of the population living in rural areas and the mean population density in the areas surveyed (Table 1). The mean population density varied from 16 persons/km2 in Nova Scotia to 4,189 persons/km2 in Vienna. The proportion of the population living in rural areas varied from 5% in Vienna to 45% in Nova Scotia. Access to PCI-hospital was also limited in Nova Scotia with only 1 PCI-hospital in this Canadian province (ratio of 900,000 persons/PCI-hospital compared with 175,000 persons/PCI-hospital in Houston, Texas).
In most surveyed countries except for Sweden, pre-hospital ECG were available only since the year 2000 (Table 2). Most ambulance personnel were trained to interpret ECG. In Vienna and France, 95% and 100%, respectively, of ambulances were staffed with physicians (Table 3), all other PHL programs surveyed had paramedics and nurses (Sweden) able to provide advanced cardiac life support (i.e., advanced care paramedics). The PHL programs in London, Vienna, Houston, Edmonton, Sweden, and Halifax had integrated regional networks to facilitate direct transfer of patients for primary PCI (Table 4). In Vienna and Sweden, all STEMI patients were transported directly to a PCI-hospital for primary PCI, except for patients who lived in very remote rural areas in Sweden. In England/Wales, at the time of this survey, there was no formal transportation arrangement for primary PCI outside London. In the greater London area, all STEMI patients were transported directly for primary PCI. In Nova Scotia, direct transfer for primary PCI was only possible for patients with STEMI living in Halifax.
Except for England/Wales, where paramedics could independently initiate PHL, PHL could only be administered after transmission of pre-hospital electrocardiogram (ECG) and authorization from responsible physicians in the other PHL programs (Table 4). In Houston, Nova Scotia, and Edmonton, PHL was administered by paramedics; in Sweden, by ambulance nurses; and in France and Vienna, PHL was administered by physicians in the ambulances.
We described the characteristics and outcomes of patients who received PHL in Tables 5 and 6.⇓⇓ Reinfarction was uncommon with cumulative incidences that ranged from 2.4% (France) to 5.8% (England/Wales). Less than 2% of PHL patients (≤0.6% in most programs) experienced in-hospital stroke. The French PHL program had the lowest mortality at 2.7% in-hospital and 4.5% at 1 year, whereas Sweden had the highest in-hospital mortality at 6.5% and 10.7% at 1 year.
Although the efficacy and safety of PHL were demonstrated in several randomized clinical trials (RCTs) (2–5), the generalizability of these results is limited by differences in characteristics of patients and systems of care in the “real-life” context. Real-life patients are often older and sicker with more comorbidities than patients enrolled in RCTs (21). Because of their generally larger samples sizes and longer follow-up durations than RCTs (22,23), data from cohort studies, such as those reported in this article, may offer invaluable insights into the real-life effectiveness of PHL.
There are several barriers to PHL implantation in North America (24). First, the cost of a PHL program may be prohibitive for many pre-hospital agencies (24). Furthermore, emergency physicians may be reluctant to authorize PHL for patients whom they have not yet evaluated for fear of litigation. There may also be misperception that PHL is not necessary considering that 79% of Americans and 59% of Canadians live within an hour of a PCI-hospital (13,26) and therefore should be able to undergo primary PCI in a timely manner. However, the preceding estimate was based purely on geographic distance and without consideration of bad weather and traffic congestion. Despite the large number of PCI-hospitals and shorter distances to PCI-hospitals in Europe, PHL remains a valuable reperfusion strategy endorsed by the European Society of Cardiology (7–9).
Pre-hospital ECG is an essential prerequisite for PHL and endorsed by the American Heart Association and American College of Cardiology (2). However, only a minority of North American pre-hospital medical services can perform ECGs in the ambulances (10,11). Transmission problems might have further prevented implementation of pre-hospital ECG in many regions. Among the PHL programs surveyed, ECG interpretation in the ambulances can either be automated (i.e., interpreted by a computer) or undertaken by paramedics or by nurses. Although ECG transmission could be helpful for patients with unclear diagnoses, well-trained paramedics and nurses could diagnose and treat most STEMI successfully without ECG transmission.
The outcomes reported in this article provided important insights into the effectiveness and safety of PHL within several different contexts and time spans. These results were similar to the outcomes reported by other American PHL programs (26). Denktas et al. (26) reported similarly low incidences of major adverse outcomes (mortality of 3.8%, stroke of 1.8%, and reinfarction of 0.8%). The higher in-hospital and 1-year mortality in patients who received PHL in Sweden, relative to PHL in other jurisdictions may be partially explained by a 5-year difference in mean age. Overall, the relatively low incidences of major adverse outcomes following PHL suggested that this reperfusion strategy could be administered safely and effectively by healthcare professionals of diverse trainings and expertise.
PHL should not be viewed as an alternate option, but rather as a complementary reperfusion strategy to primary PCI for patients with STEMI. An ideal PHL program would incorporate formal protocols that identify patients who would benefit from direct transport for primary PCI where appropriate and those who would benefit from very early FL. This would need to take account of who the patient is (i.e., patient characteristics), where the patient is (i.e., distance from a PCI-hospital), what is available for treatment, and how soon the patient presents after onset of symptoms. In this way, tailored reperfusion therapy would be provided for each STEMI patient depending on his or her circumstances.
In addition to facilitating transfer, integrated regional networks of PCI-hospitals can be invaluable for continuing cardiac care following PHL. After PHL, patients can be transferred to PCI-hospitals and then triaged for selective nonurgent PCI for patients with successful coronary flow restoration with PHL or rescue PCI for patients who did not have unsuccessful PHL. By expediting coronary reperfusion, PHL can prevent undue time delays with the associated increased risks of mortality and irreversible myocardial damage. In addition, PHL may reduce the economic burden of STEMI by decreasing the need for urgent PCI outside regular working hours.
First, comparison of morbidity and mortality data across PHL programs could not be undertaken due to the lack of individual patient data. Second, our description of structures and processes of the PHL programs relied on a self-administered survey by the different administrators. Although we did query some inconsistencies and cross-check with other sources of information (27) and other experts in reperfusion therapy, we did not systematically validate all responses provided by the investigators. Third, our survey did not incorporate economic and quality assurance aspects (e.g., paying process of the fibrinolytic drugs, training and monitoring of outcomes). Finally, the outcome data were derived from observational studies and therefore were subject to all the biases inherent to this type of study such as selection, confounding, and information biases. Despite these limitations, we believe that the outcome data of PHL, as reported in this manuscript, provide valuable information and may serve as benchmark for other programs of reperfusion therapy.
PHL has been successfully deployed in a wide range of geographic territories with varying population densities; access to PCI-hospitals and annual incidences of STEMI. PHL systems comprise a variety of different processes that could be adapted to local contexts. PHL can be safely delivered by healthcare professionals with different levels of training and expertise in a wide variety of settings. Even in areas with rapid access to primary PCI, PHL remains a valuable reperfusion strategy, for patients with expected prolonged time delay from first medical contact to coronary flow restoration by primary PCI.
Combining PHL with formal protocols for direct transportation of patients to a PCI-hospital for primary PCI would allow tailored reperfusion therapy for patients with STEMI. Insights from a variety of international settings may promote widespread use of PHL and increase timely coronary reperfusion worldwide.
The authors wish to dedicate this article to the memory of Dr. Ulf Stenestrand who coauthored this article. He inspired us with his passion and commitment to improve global cardiovascular health. May his memory continue to live.
The authors also wish to acknowledge the invaluable assistance of Dr. Paul Armstrong, Dr. David Persse, and Dr. Lars Wallentin in making this international collaboration possible.
To see the questionnaires, please see the online version of this article.
The MINAP (Myocardial Ischemia National Audit Project) and Cardiovascular Health Nova Scotia were funded mainly by government health agencies. The AMICO, RIKS-HIA, and Vienna STEMI Registry received partial support from pharmaceutical companies, and the Vienna STEMI Registry was partially supported by the Association for the Promotion of Research in Arteriosclerosis, Thrombosis, and Vascular Biology. The Unités des Soins Intensives Coronariens 2000 registry was funded by Aventis. The FAST-MI is a registry of the French Society of Cardiology, funded by unrestricted grants from Pfizer and Servier, and by an additional grant from the Caisse Nationale d'assurance-maladie (National Health Insurance system). Dr. Huynh has received minor grants for organization of educational symposia from RocheCanada in 2009 and 2010. Dr. O'Loughlin holds a Canada Research Chair in the Early Determinants of Adult Chronic Disease. Dr. Stenestrand was the President of the RIKS-HIA Registry. Dr. Schull holds a Canadian Institutes of Health Research Applied Chair in Health Services and Policy Research. Dr. Welsh has received research grants from Boehringer Ingelheim, AstraZeneca, Sanofi-Aventis, Eli Lilly, Portola, Abbott, and Medtronic; and he was on the advisory boards for and received honorarium from AstraZeneca, Bristol-Myers Squibb, Sanofi-Aventis, Roche, and Eli Lilly. Dr. Tu is supported by a Tier 1 Canada Research Chair in Health Services Research and a career investigator award from the Heart and Stroke Foundation of Ontario. Dr. Danchin has received lecturing/consulting fees from AstraZeneca, Eli Lilly, Novo, Sanofi-Aventis and Servier; lecture fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Menarini, Merck-Serono, MSD-Schering-Plough, Servier, and Sanofi-Aventis; and grant support from AstraZeneca, Eli Lilly, GlaxoSmithKline, Merck-Schering-Plough, Novartis, Pfizer, Sanofi-Aventis, Servier and The Medicines Company. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Dr. Ulf Stenestrand is deceased.
- Abbreviations and Acronyms
- fibrinolytic therapy
- percutaneous coronary intervention
- pre-hospital fibrinolysis
- randomized controlled trial
- ST-segment elevation myocardial infarction
- Received May 12, 2011.
- Accepted May 25, 2011.
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