Timing of aspirin administration as a determinant of survival of patients with acute myocardial infarction treated with thrombolysis

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Abstract

Unlike thrombolytic agents, there are conflicting data regarding the time-dependent effect of aspirin treatment on outcome in acute myocardial infarction (AMI). We sought to evaluate the impact of timing of aspirin administration (before vs after thrombolysis) on mortality of patients with AMI. Our study included 1,200 patients with ST elevation AMI treated with thrombolysis. Early (n = 364) versus late (n = 836) users were defined as those receiving emergency aspirin before versus after initiation of thrombolysis, respectively. Time (median) from symptom onset to initiation of aspirin treatment was significantly shorter in early versus late users (1.6 vs 3.5 hours; p <0.001). There were no significant differences between the 2 groups with respect to baseline clinical characteristics. Early aspirin users were more likely to develop reischemia, to be treated with β blockers, to be referred to coronary angiography, percutaneous transluminal coronary angioplasty, or coronary artery bypass graft surgery. Early users experienced lower mortality at 7 days (2.5% vs 6.0%, p = 0.01), 30 days (3.3% vs 7.3%, p = 0.008), and 1 year (5.0% vs 10.6%, p = 0.002) than late users. This survival benefit persisted for patients with and without previous aspirin therapy or revascularization and after adjustment for baseline characteristics and therapies at 7 days (odds ratio 0.36, 95% confidence interval 0.15 to 0.79), at 30 days (odds ratio 0.39, 95% confidence interval 0.17 to 0.82), and at 1 year (odds ratio 0.41, 95% confidence interval 0.21 to 0.74). Our study proposes a time-dependent benefit from aspirin in patients with AMI treated with thrombolysis.

Section snippets

Study patients:

The study population was drawn from the ARGAMI-2 study, a double-blind, prospective, 3-arm, parallel, randomized trial comparing 2 dosages of argatroban versus intravenous heparin as adjunctive therapy with recombinant tissue plasminogen activator (rt-PA) or streptokinase in patients with AMI.1 The study was conducted between December 12, 1995, and March 23, 1997, in 25 medical centers in Israel. A total of 1,200 patients aged ≥21 years who provided written consent were included in the trial.

Baseline characteristics:

Among the 1,200 patients enrolled in the study, 364 (30%) received aspirin before initiation of thrombolytic infusion (early users). The remaining 836 patients (70%) were given the first dose of aspirin after thrombolytic infusion was initiated (late users).

The exact time interval from onset of chest pain to administration of aspirin was obtained in 104 of the early aspirin users and in 809 of the late aspirin users. The median time interval was significantly shorter for early versus late

Discussion

The main new finding of our study is a striking reduction in mortality of patients with AMI who are treated with emergency aspirin before versus those who are treated after initiation of thrombolysis infusion. This benefit persists after adjustment for differences between groups and has been identified in patients with and without previous aspirin treatment and with and without revascularization.

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