Long-term nitrate use in acute myocardial infarction (The Heart Institute of Japan, Department of Cardiology nitrate evaluation program)

Background The lack of any randomized controlled trials demonstrating a beneficial effect of nitrates for the secondary prevention of coronary artery disease leads to a negative recommendation in current practice guidelines. The aim of the present study was to examine the efficacy of nitrate therapy for the treatment of acute myocardial infarction (AMI) in the contemporary revascularization era. Methods and results Of 2,736 consecutive patients with AMI (1,677 on nitrate therapy and 1,059 control patients not receiving nitrates), 1,766 patients were matched according to a propensity score (883 receiving nitrates and 883 control subjects). Before propensity score matching, the patients treated with nitrates were significantly older, had a higher Killip class, and underwent less aggressive revascularization and less modern pharmacotherapy compared with the patients who were not given nitrates. A total of 117 patients (11.0%) died in the control group and 317 patients (18.9%) in the nitrate group (hazard ratio, 1.70; 95% CI, 1.38-2.10; P < 0.001) during a 5-year follow-up period. In contrast, among propensity score-matched patients, 110 patients (12.5%) died in the control group and 126 patients died (14.3%) in the nitrate group (hazard ratio, 1.06; 95% CI 0.82-1.36, P=0.678). The 1-, 3- and 5-year cumulative mortality rates (Kaplan-Meier method) were respectively 4.5%, 9.8%, and 14.1% in the control group versus 5.2%, 9.8%, and 14.8% in the nitrate group. There were also no statistical or clinical differences between the two matched groups with regard to the other endpoints assessed. Conclusions Our results suggest that nitrate therapy does not increase mortality and cardiac events in AMI patients. Our results differ from those of previous observational studies, suggesting that new prospective randomized clinical trials are needed in the current revascularization era.