Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Prehospital thrombolytic therapy reduced mortality in acute MI

ACP J Club. 1996 July-Aug;125:6. doi:10.7326/ACPJC-1996-125-1-006


Source Citation

Rawles J. Magnitude of benefit from earlier thrombolytic treatment in acute myocardial infarction: new evidence from Grampian region early anistreplase trial (GREAT). BMJ. 1996 Jan 27;312:212-6. [PubMed ID: 8563585]


Abstract

Objective

To determine the benefit of earlier thrombolysis in patients with acute myocardial infarction (MI) who participated in the Grampian Region Early Anistreplase Trial (GREAT).

Design

Randomized, double-blind, controlled trial with 30-month follow-up.

Setting

Teaching hospitals in Aberdeen, Scotland, and 29 rural practices.

Patients

311 patients (mean age 63 y, 70% men) with suspected acute MI who were seen at home by a general practitioner within 4 hours of the onset of symptoms. Exclusion criteria included thrombolytic therapy or bleeding within the past 6 months; surgery or major trauma in the past 10 days; cerebrovascular accident or neurosurgery within 2 months; thrombocytopenia or hemorrhagic diathesis; pregnancy; diabetic proliferative retinopathy; blood pressure > 200/100 mm Hg; or recent resuscitation with chest compression. Follow-up was complete.

Intervention

163 patients received 30 units of anistreplase intravenously at home (median, 101 min from start of symptoms), followed by placebo in the hospital. 148 patients received placebo at home, followed by 30 units of anistreplase intravenously in the hospital (median, 240 min from start of symptoms).

Main outcome measures

Mortality and lives saved/h of earlier treatment.

Main results

At 30 months, fewer deaths occurred in patients who had received home treatment than in those who had received hospital treatment (17% vs 32%, P = 0.001) (Table). In patients presenting 2 hours after the start of symptoms, each delay in thrombolysis of 1 hour led to the loss of 21 lives/1000 within 30 days (CI 1 to 94 lives/1000, P = 0.03) and 69 lives/1000 within 30 months (CI 16 to 141 lives/1000, P = 0.001).

Conclusion

Compared with thrombolysis provided at the hospital, prehospital thrombolysis resulted in a substantial mortality benefit that continued to grow after hospital discharge.

Sources of funding: SmithKline Beecham and Acute Healthcare Research Committee of the Scottish Home and Health Department.

For article reprint: Dr. J. Rawles, Brunnion Minor, Lelant Downs, Hayle, Cornwall TR27 6NT UK. FAX 44-1736-740067.


Table. Prehospital vs hospital anistreplase treatment in acute myocardial infarction*

Outcome at 30 mo Prehospital anistreplase Hospital anistreplase RRR (95% CI) NNT (CI)
Mortality 17% 32% 48% (21 to 66) 7 (4 to 17)

*Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.


Commentary

More than 20 studies have shown that thrombolytic therapy can be safely administered outside the hospital setting and can reduce treatment delays. The Myocardial Infarction Triage and Intervention Trial (1) showed no difference in outcomes whether treatment was done before arrival at the hospital or in the hospital but did show that initiating thrombolytic therapy within 70 minutes of symptom onset reduced mortality from 9% to 1%. Only 4% of the screened patients were eligible for thrombolysis before hospital arrival, which highlights the logistical problem to this approach. The European Myocardial Infarction Project (2) reduced the time to treatment by 55 minutes, but more adverse events occurred while transporting patients who received treatment before hospital arrival. The pooled results from 6 major randomized trials showed a 17% reduction in mortality with therapy administered before hospital arrival (3).

This report from GREAT also supports that a greater benefit is derived from earlier thrombolytic treatment. The study does not give very precise estimates of mortality benefit according to delay of treatment, so the estimate of lives saved/1000 patients may be optimistic. Data from 2 other major trials (4, 5) suggest that 10 lives/1000 treated patients are saved for every 1-hour reduction in time to therapy. In contrast to GREAT, the mega-trials with in-hospital thrombolysis do not show further survival benefit after hospital discharge.

Thrombolytic therapy before hospital arrival seems beneficial, but logistical, medical, and legal barriers to widespread implementation exist in North America. Therefore, the current emphasis is on reducing the time to treatment in the emergency department by the same 30 to 60 minutes achieved in the prehospital studies. In the future, half-dose bolus therapy with alteplase, reteplase, or temecteplase may offer the potential of safely initiating therapy before hospital arrival and then committing to more thrombolysis or other therapies after an evaluation in the emergency department.

Eric R. Bates, MD
University of Michigan Medical CenterAnn Arbor, Michigan, USA


References

1. Weaver DW, Cerqueira M, Hallstrom AP, et al. Prehospital-initiated vs hospital-initiated thrombolytic therapy. The Myocardial Infarction Triage and Intervention Trial. JAMA. 1993;270:1211-6.

2. The European Myocardial Infarction Project Group. Prehospital thrombolytic therapy in patients with suspected acute myocardial infarction. The European Myocardial Infarction Project Group. N Engl J Med. 1993; 329:383-9.

3. 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.

4. Williams DO, Braunwald E, Knatterud G, et al. Mortality and prehospital thrombolysis for acute myocardial infarction. A meta-analysis. Circulation. 1992;84:533-42.

5. The GUSTO Investigators. One-year results of the Thrombolysis in Myocardial Infarction investigation (TIMI) Phase II Trial. N Engl J Med. 1993;329:673-82.