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


Therapeutics

At-home thrombolysis reduced all-cause mortality and morbidity in patients with acute myocardial infarction

ACP J Club. 1993 Jan-Feb;118:1. doi:10.7326/ACPJC-1993-118-1-001


Source Citation

GREAT Group. Feasibility, safety, and efficacy of domiciliary thrombolysis by general practitioners: Grampian region early anistreplase trial. BMJ. 1992 Sep 5;305:548-53.


Abstract

Objective

To evaluate the efficacy and safety of at-home thrombolysis by general practitioners in patients with suspected acute myocardial infarction.

Design

Randomized, double-blind, placebo-controlled trial.

Setting

29 rural practices admitting patients to teaching hospitals in Aberdeen, Scotland.

Patients

311 patients (mean age 63 y, 216 men) with suspected acute myocardial infarction seen at home by a general practitioner within 4 hours of onset f symptoms. Exclusion criteria were thrombolytic therapy within the past 6 months; surgery or major trauma in the past 10 days; bleeding within the past 6 months; cerebrovascular accident or neurosurgery within 2 months or an intracranial neoplasm or aneurysm; thrombocytopenia or hemorrhagic diathesis or anticoagulant treatment; pregnancy; diabetic proliferative retinopathy; blood pressure > 200/100 mm Hg; or recent resuscitation with chest compression.

Intervention

163 patients received a home intravenous injection of anistreplase, 30 units, followed by placebo in the hospital. 148 patients received a home intravenous injection of placebo, followed by an injection of 30 units of anistreplase in the hospital.

Main outcome measures

Time to thrombolysis, death, Q-wave infarction, left ventricular function, and adverse events.

Main results

The median times to home and hospital anistreplase injections after the onset of symptoms were 101 and 240 minutes, respectively. At 3 months, death (from all causes) occurred in 13 patients (8%) receiving anistreplase at home compared with 23 patients (16%) receiving anistreplase in the hospital (difference -8%, 95% CI -15% to -1%, P = 0.04) (Table). Q-wave infarcts occurred in 65 of the 122 patients (53%) with confirmed infarction receiving treatment at home compared with 76 of the 112 patients (68%) receiving treatment in the hospital (difference -15%, CI -27% to -2%, P = 0.02) (Table). An estimate of left ventricular function—mean stroke distance by Doppler ultrasound—tended to be higher in the group of patients given anistreplase at home within 2 hours of onset of symptoms. Hypotension was the most frequent adverse event after thrombolysis, recorded in 7% of patients. Major bleeding was not more common with anistreplase given in the home.

Conclusion

Giving anistreplase at home rather than later administration in the hospital led to a reduction in 3-month all-cause mortality and fewer Q-wave infarcts.

Source of funding: Not stated.

For article reprint: Dr. J.M. Rawles, Medicines Assessment Research Unit, University of Aberdeen, Foresterhill, Aberdeen AB9 2ZD, United Kingdom. FAX 44-2-24-685-307.


Table. At-home anistreplase vs placebo for acute myocadial infarction (MI)

Outcomes at 3 months Anistreplase Placebo RRR (95% CI) NNT (CI)
Death 8.0% 15.5% 49% (4 to 73) 13 (7 to 219)
Q-wave MI 53.3% 67.9% 22% (3 to 37) 7 (4 to 49)

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


Commentary

A superficial review of this study would suggest that it has little value to clinical practice in North America. Ten minutes from call for medical assistance to arrival in the home by a general practitioner to evaluate a complaint of chest pain is shorter than the registration process in most of our emergency units. Two strong messages, however, are again sent across the Atlantic. First, thrombolytic therapy within 2 hours of symptom onset of acute myocardial infarction dramatically decreases morbidity and mortality compared with later treatment or no treatment. Prehospital administration of therapy is one way to accomplish this, but the time and expense of developing and maintaining this service may be prohibitive. Unfortunately, public education programs have not decreased time to presentation for treatment. Decreasing emergency room time to treatment from a mean of 80 minutes to 20 minutes by considering chest pain evaluation a medical emergency is the most practical solution and would bring 50% of the patients who present within 6 hours of symptom onset to treatment within 2 hours.

Second, in this study, general practitioners made the diagnosis of acute myocardial infarction and administered thrombolytic therapy. The rate of false-positive diagnosis was low (2%), although we are not given the false-negative rate. This questions the necessity of involving specialists, with the attendant delay in treatment, in the initial assessment and treatment of patients with myocardial infarction.

Compared with streptokinase, the standard thrombolytic, anistreplase has more adverse effects (1)* and costs approximately 10 times as much but requires a shorter (5 min) infusion time.

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


Reference

1. ISIS-3 Collaborative Group. ISIS-3: a randomised comparison of streptokinase vs tissue plasminogen activator vs anistreplase and of aspirin plus heparin vs aspirin alone among 41,299 cases of suspected acute myocardial infarction. ISIS-3 (Third International Study of Infarct Survival) Collaborative Group. Lancet. 1992;339:753-70.

*Subsequent to the ISIS trial, the manufacturer of anistreplase has decided not to market the drug in Canada, although it is still available in the United States.— The Editor


Editorial Comment

Long-term follow-up in the GREAT (Grampian Region Early Anistreplase Trial) shows that the early benefit attained by avoiding delays in the administration of thrombolytic therapy may lead to even larger benefits in the long term, presumably by myocardial salvage and its related benefits (2).

2. Rawles JM. Quantification of the benefit of earlier thrombolytic therapy: five-year results of the Grampian Region Early Anistreplase Trial (GREAT). Am J Coll Cardiol. 1997;30:1181-6.