Intermittent nitrate therapy for prior myocardial infarction does not induce rebound angina nor reduce cardiac events

Abstract

Objective: Long-term nitrate therapy for ischemic heart disease may cause drug tolerance which diminishes its beneficial effects; consequently, intermittent administration of nitrates is recommended. With this regimen, however, the potential occurrence of rebound angina during the nitrate-free intervals is a source of concern. Subjects and Methods: We carried out a retrospective study of 606 patients to determine whether rebound angina occurred when conventional continuous nitrate administration was replaced by intermittent administration as part of a long-term therapy protocol for prior myocardial infarction. The subjects were receiving treatment for myocardial infarction and included 293 patients treated with nitrates (Nitrate group) and 313 patients who were not (No-nitrate group). The former included 186 patients who received intermittent nitrate administration (Intermittent group) and 107 patients who received continuous administration (Continuous group). The mean period of observation was 4.3±1.6 months. Results: There were no cases of rebound angina in the Intermittent group. Cardiac events occurred in one case in the No-nitrate group (0.3%), in 4 cases in the Continuous group (3.7%) and in 2 cases in the Intermittent group (1.1%). The incidence of cardiac events was thus significantly increased in the Continuous group compared to the No-nitrate group (p<0.05; odds ratio 9.06; 95% CI 1.41-58.28). The Intermittent group did not significantly differ from the No-nitrate group in the incidence of cardiac events. Conclusion: It is concluded that intermittent administration of nitrates does not cause rebound angina and is therefore safe. A randomized controlled trial is needed to find the long-term effect on cardiac events.