BMJ  2003;327:1-2 (5 July), doi:10.1136/bmj.327.7405.1

Editorial

Prehospital thrombolysis

Will pave the way for accelerated management of acute myocardial infarction

The national service framework for coronary heart disease has set a series of challenging targets for medical practitioners across a range of disciplines, aimed at reducing this leading cause of mortality in the United Kingdom. In many areas, notably the delivery of secondary prevention after acute myocardial infarction, these challenges have largely been met. The benefits of prompt thrombolysis for acute myocardial infarction are well recognised,¹ and early patency of the relevant artery is now the holy grail of management. Difficulties remain, however, in delivering effective and timely treatment, with a target "call to needle" time of less than 60 minutes stated by the national service framework.² Reorganisation of in-hospital care (devolving the administration of thrombolysis to emergency departments, appointment of specialised chest pain triage nurses, and use of bolus lytic agents) has brought about great advances in the past three years, and 76% of eligible patients now receive thrombolysis within 30 minutes of arrival in hospital.³ Problems surrounding transfer to hospital remain, however, particularly for patients who live remote from a medical facility.

The feasibility of prehospital thrombolysis has been shown in studies that have used a variety of models for delivery of treatment, and meta-analysis has confirmed a reduction of all cause in-hospital mortality by 2% per hour of earlier treatment, with no important associated hazards.⁴ In this issue (p 22), Pedley et al describe their experience of adopting this strategy after the closure of the coronary care facility of a small rural district general hospital within their region of Scotland.⁵ They report an impressive median call to needle time of 52 minutes for patients who received prehospital thrombolysis, compared with 80 minutes in a cohort of urban residents and 125 minutes in a similar rural control group treated conventionally. Importantly, 64% of patients treated before arrival in hospital received thrombolysis within 60 minutes of medical contact, compared with 4% of the controls. This adopted policy seemed to be of low risk, caused minimal obstruction to practice, and ran smoothly in a short time frame.

Primary angioplasty offers an alternative means of early restoration of coronary flow in acute myocardial infarction and may be more effective than thrombolytic treatment, as it achieves higher coronary arterial patency rates and improved coronary flow. Other advantages of this mechanical approach include lower rates of reinfarction, bleeding, and stroke, coupled with earlier revascularisation, risk stratification, and rehabilitation. In a recent meta-analysis of the available randomised trials,⁶ primary angioplasty was superior to thrombolysis in reducing early mortality (7% v 9%), non-fatal reinfarction (3% v 7%), stroke (1% v 2%), and a combination of these three end points (8% v 14%) (P < 0.001 for all comparisons). These benefits were sustained at long term follow up, were independent of the thrombolytic agent used, and occurred whether or not the patient required transfer for primary angioplasty. Further recent nationwide studies in the Czech Republic⁷ and Denmark⁸ have confirmed the safety and feasibility of inter-hospital transportation for primary angioplasty and show that clinical advantages persist despite the inherent delay compared with on-site thrombolysis.⁹

The advantages of thrombolysis and primary angioplasty may be complementary and not mutually exclusive. Potential benefits of using thrombolytics or platelet glycoprotein IIb/IIIa receptor antagonists as a preamble to urgent "facilitated" angioplasty include rapid restoration of brisk coronary flow, improvements in angioplasty outcome after pharmacological pretreatment, and enhanced tissue level reperfusion and myocardial salvage.¹⁰ Thus further reductions in mortality and morbidity may be obtained if transfer time could be utilised to administer optimal lytic regimens prior to urgent angioplasty. The adoption of this approach would require a fleet of modern intensive care ambulances with electrocardiographic monitoring, defibrillators, and modern communication facilities, and staffed by trained paramedics and nurses with direct access to angioplasty centres, thereby avoiding time consuming stops in local emergency departments or coronary care units. Given that only 10 ambulance trusts in the United Kingdom are currently trained and equipped to provide prehospital thrombolysis,¹¹ substantial funds would be needed for such developments.

In the real world, of course, immediately providing primary or facilitated angioplasty for all patients with evolving acute myocardial infarction is impractical due to the limited number of (already overburdened) centres where the procedure can be done in a timely fashion by experienced operators. Indeed, a recent manpower statement from the British Cardiac Society concluded that proposed expansions in coronary intervention, including the adoption of angioplasty for infarcts, would require an additional two to three consultant operators in each interventional centre in the United Kingdom, allowing for 2000-3000 procedures per million population; 24 hour emergency cover; and application of the European Working Time Directive.¹²

Thus although the anticipated increase in infarct angioplasty may radically alter acute management in future, early thrombolysis remains the current goal for reperfusion. In the immediate term, prehospital thrombolysis should be strongly considered in rural communities and congested urban areas where transfer to hospital is likely to be delayed. As this practice evolves, the associated changes in infrastructure and ambulance service provision will enable further advances in the rapid treatment of acute myocardial infarction, including the widespread adoption of facilitated and primary angioplasty in dedicated regional myocardial infarction centres.

Department of Cardiology, North-West Regional Cardiothoracic Centre, Wythenshawe Hospital, Manchester M23 9LT (Bernard.Prendergast{at}smuht.nwest.nhs.uk)

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Papers p 22

Competing interests: None declared.

References

1. Fibrinolytic Therapy Trialists' (FTT) Collaborative Group. Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Lancet 1994;343: 311-22.[CrossRef][ISI][Medline]
2. Department of Health. National service framework for coronary heart disease. 2000. www.doh.gov.uk/nsf/coronary.htm (accessed 30 Jun 2003).
3. Myocardial Infarction National Audit Project. MINAP–second heart attack audit results–progress continues. http://www.rcplondon.ac.uk/news/news.asp?PR_id=181 (accessed 30 Jun 2003).
4. Morrison LJ, Verbeek PR, McDonald AC, Sawadsky BV, Cook DJ. Mortality and prehospital thrombolysis for acute myocardial infarction: a meta-analysis. JAMA 2000;283: 2686-92.[Abstract/Free Full Text]
5. Pedley DK, Bissett K, Connolly E, Goodman CG, Golding I, Pringle TH, et al. Prospective observational cohort study of time saved by prehospital thrombolysis for ST elevation myocardial infarction delivered by paramedics. BMJ 2003;327: 22-6.[Abstract/Free Full Text]
6. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 2003;361: 13-20.[CrossRef][ISI][Medline]
7. Widimsky P, Budesinsky T, Vorac D, Groch L, Zelizko M, Aschermann M, et al. Long distance transport for primary angioplasty vs immediate thrombolysis in acute myocardial infarction. Final results of the randomized national multicentre trial–PRAGUE-2. Eur Heart J 2003;24: 94-104.
8. Danish multicenter randomized study on thrombolytic therapy versus acute coronary angioplasty in acute myocardial infarction (DANacute myocardial infarction-2). Late breaking clinical trials. American College of Cardiology, March 2002. www.danami-2.dk (acccessed 30 Jun 2003).
9. Zijlstra F, Patel A, Jones M, Grines CL, Ellis S, Garcia E, et al for the PCAT collaboration. Clinical characteristics and outcome of patients with early (< 2h), intermediate (2-4h) and late (> 4h) presentation treated by primary coronary angioplasty or thrombolytic therapy for acute myocardial infarction. Eur Heart J 2002;23: 550-7.[Abstract/Free Full Text]
10. Li RH, Herrmann HC. Facilitated percutaneous coronary intervention: a novel concept in expediting and improving acute myocardial infarction care. Am Heart J 2000;140: S125-35.[CrossRef][ISI][Medline]
11. Ambulance Service Association National Clinical Effectiveness Programme. www.asancep.org.uk (accessed 30 Jun 2003).
12. British Cardiac Society. BSC Working Group on Cardiology Workforce Requirements. 12 June 2003. www.bcs.com/documents/workforce_document.pdf (accessed 30 Jun 2003).

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