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Meta-analysis: Streptokinase reduces mortality in suspected myocardial infarction

ACP J Club. 1991 Mar-April;114:35. doi:10.7326/ACPJC-1991-114-2-035

Source Citation

Midgette AS, O'Connor GT, Baron JA, Bell J. Effect of intravenous streptokinase on early mortality in patients with suspected acute myocardial infarction. A meta-analysis by anatomic location of infarction. Ann Intern Med. 1990;113:961-8.



To examine the effectiveness of streptokinase on early mortality in suspected acute anterior myocardial infarction and inferior myocardial infarction.

Data sources

A search was done using MEDLINE and the bibliographies of relevant articles for studies in English on the use of intravenous streptokinase in acute myocardial infarction for the period from 1966 to 1989.

Study selection

Randomized trials using intravenous streptokinase in a dose of 1.5 million units, with or without other agents, were selected by reviewing the methods section of each study. The comparison groups were required to use the same treatment protocol, except for use of streptokinase. Of 140 identified studies, 6 met these criteria.

Data extraction

Data were extracted on specific location of infarct, time until beginning of treatment, survival data (21 to 35 d), and additional treatments according to pre-established criteria. All data were extracted by 2 independent observers with identical results.

Main results

The numbers of patients in the trials ranged from 219 to 17 187; 79% were men; mean (or median) age ranged from 57 to 65 years. All studies included data on location of suspected infarction; electrocardiographic criteria used to determine location varied among trials. Of 9155 patients with suspected acute anterior myocardial infarction, the overall mortality was 17% in the control group compared with 13% for patients assigned to streptokinase. {This absolute risk reduction (ARR) of 4% means that 21 patients would need to be treated with streptokinase (compared with various control treatments) to prevent 1 additional death, 95% CI 14 to 48; the relative risk reduction was 28%, CI 21% to 35%}.* Of 9650 patients with suspected acute inferior myocardial infarction, the overall mortality was 8% in the control group and 7% in the group assigned to streptokinase {ARR 1%, CI -0.2% to 1.8%}*.


Patients with suspected acute anterior or inferior myocardial infarctions have lower early mortality when treated with streptokinase. The benefit is greater for patients with anterior infarctions.

Source of funding: Veterans Affairs General Medicine Fellowship.

Address for article reprint: Dr. A.S. Midgette, Veterans Affairs Hospital, White River Junction, VT 05001, USA.

*Numbers calculated from data in article.


Inferior myocardial infarction (MI) is generally distinguished from anterior infarction because some clinical manifestations, such as bradycardia, depend on infarct location. Anterior MIs are also generally larger than inferior MIs and because infarct size correlates with mortality, anterior MIs are associated with a higher mortality rate. Infarction in either location, however, results from acute coronary thrombosis.

The meta-analysis by Midgette and co-workers has 3 key limitations. First, the primary question of interest is whether thrombolytic therapy should be given to patients with inferior infarction, but the authors included only randomized trials of streptokinase, excluding trials of other thrombolytic agents that also provide data relevant to this decision. Second, the reasons for excluding 134 of 140 identified articles from the meta-analysis were not provided. Finally, formal statistical comparisons of results in inferior compared with anterior infarction were not presented.

Despite these limitations, this study makes 2 valuable points. First, thrombolytic therapy reduces mortality in both anterior and inferior MIs (which is not surprising given that the same mechanism produces both types). Second, the absolute benefit in anterior MI (21 patients treated to save 1 life) is much higher than in inferior MI (91 patients treated to save 1 life),* but only because the mortality rate is higher for patients with anterior MI. Because the risk for thrombolytic therapy does not vary according to infarct location, the benefit of therapy is more clearly worth the risk for most patients with anterior MI than for most patients with inferior MI. Therapeutic decision making should be individualized, however, because patients often have findings that alter their risk. Patients with inferior MIs at higher risk (for example, patients with precordial ST-depression or complete heart block) probably have more to gain from thrombolytic therapy, especially if treated soon after symptom onset.

Mark A. Hlatky, MD
Stanford University School of MedicineStanford, California, USA

*The authors estimated that 125 patients were needed to treat to save 1 life, using a weighted analysis — The Editor

Two randomized trials (1, 2) evaluating the effectiveness of streptokinase have been published since this report:


1. ISIS-3 (Third International Study of Infarct Survival) Collaborative Group. ISIS-3: a randomized 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. Lancet. 1992 Mar 28;339:753-70.

2. The GUSTO Investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med. 1993 Sep 2;329:673-82.