Studies of outcome following myocardial infarction showed that in suitable patients, fibrinolytic therapy typically prevents 20 to 30 deaths per 1,000 patients treated within the first month. Early aspirin therapy also showed the potential to prevent about 25 deaths and 10 to 15 non-fatal reinfarctions or strokes per 1,000 patients in the month following infarction. Baigent and colleagues conducted a randomized, placebo-controlled study to assess the long-term survival of patients with myocardial infarction receiving either or both of these therapies.
The authors used data from 17,187 patients with suspected acute myocardial infarction who were enrolled in the Second International Study of Infarct Survival from 1985 through 1987. These patients were randomly assigned to receive either 1.5 million IU of streptokinase or placebo for one hour, and either aspirin (162.5-mg, enteric-coated tablets) or placebo daily for one month. Compliance with the assigned treatments was high, and use of additional treatment was at the discretion of the physicians.
Follow-up data were available for about 95 percent of all patients up to 1990, and for 6,213 British patients up to mid-1997. In the overall population studied, there were 1,841 deaths recorded during the first 35 days; 991 deaths from day 36 through the end of year one; 1,478 deaths during years two through four; and 1,230 deaths during years five through 10. Patients receiving streptokinase had 29 fewer early deaths per 1,000 patients during the first 35 days of follow-up than those receiving placebo. This benefit persisted and resulted in 28 fewer deaths for 1,000 patients treated after four years and 23 fewer deaths for 1,000 patients treated after 10 years. The effect was not restricted to specific groups of patients. In particular, patients 70 years and older appeared to benefit as much as younger patients did. Over time there was no gain in survival or any evidence of a “catching up” in mortality following the initial improvement with early streptokinase therapy.
Compared with patients receiving placebo, patients treated with aspirin also showed a significant reduction in early mortality, with 26 fewer deaths per 1,000 patients treated during the first 35 days. As with streptokinase therapy, little further benefit or loss was observed during long-term follow-up. The benefits of the two treatments were additive. The early survival benefit of treatment with the combination of streptokinase plus aspirin resulted in approximately 55 fewer deaths per 1,000 patients by day 35. This benefit persisted in the longer term, with approximately 42 fewer deaths per 1,000 patients treated at 10 years.
The authors conclude that the early survival benefit produced by treatment with both forms of fibrinolytic therapy in patients with acute myocardial infarction appears to be maintained for at least 10 years.