BACKGROUND: There is conclusive evidence from clinical trials that reduction of mortality by fibrinolytic therapy in acute myocardial infarction is related to the time elapsing between onset of symptoms and commencement of treatment. However, the exact pattern of this relation continues to be debated. This paper discusses whether or not appreciable additional gain can be achieved with very early treatment. METHODS: The relation between treatment delay and short-term mortality (up to 35 days) was evaluated using tabulated data from all randomised trials of at least 100 patients (n = 22; 50,246 patients) that compared fibrinolytic therapy with placebo or control, reported between 1983 and 1993. FINDINGS: Benefit of fibrinolytic therapy was 65 (SD 14), 37 (9), 26 (6) and 29 (5) lives saved per 1000 treated patients in the 0-1, 1-2, 2-3, and 3-6 h intervals, respectively. Proportional mortality reduction was significantly higher in patients treated within 2 h compared to those treated later (44% [95% CI 32, 53] vs 20% [15, 25]; p = 0.001). The relation between treatment delay and mortality reduction per 1000 treated patients was expressed significantly better by a non-linear (19.4-0.6x(+)29.3x-1) than a linear (34.7 - 1.6x) regression equation (p = 0.03). INTERPRETATION: The beneficial effect of fibrinolytic therapy is substantially higher in patients presenting within 2 h after symptom onset compared to those presenting later.
BACKGROUND: There is conclusive evidence from clinical trials that reduction of mortality by fibrinolytic therapy in acute myocardial infarction is related to the time elapsing between onset of symptoms and commencement of treatment. However, the exact pattern of this relation continues to be debated. This paper discusses whether or not appreciable additional gain can be achieved with very early treatment. METHODS: The relation between treatment delay and short-term mortality (up to 35 days) was evaluated using tabulated data from all randomised trials of at least 100 patients (n = 22; 50,246 patients) that compared fibrinolytic therapy with placebo or control, reported between 1983 and 1993. FINDINGS: Benefit of fibrinolytic therapy was 65 (SD 14), 37 (9), 26 (6) and 29 (5) lives saved per 1000 treated patients in the 0-1, 1-2, 2-3, and 3-6 h intervals, respectively. Proportional mortality reduction was significantly higher in patients treated within 2 h compared to those treated later (44% [95% CI 32, 53] vs 20% [15, 25]; p = 0.001). The relation between treatment delay and mortality reduction per 1000 treated patients was expressed significantly better by a non-linear (19.4-0.6x(+)29.3x-1) than a linear (34.7 - 1.6x) regression equation (p = 0.03). INTERPRETATION: The beneficial effect of fibrinolytic therapy is substantially higher in patients presenting within 2 h after symptom onset compared to those presenting later.