Randomized clinical trials of transdermal nitroglycerin systems for the treatment of angina: a meta-analysis.

The efficacy of transdermal nitrate patches at 24 hours after application remains controversial. Definitive evaluation has been limited because most randomized trials have had relatively small sample sizes. Therefore, we performed a meta-analysis and combined the results of 17 trials. We assessed exercise test duration as the primary end point. At 3 to 4 hours after patch application, there was a 77-second increase in exercise duration (p = 0.02) for a 5 mg/24 hour dose and a 114-second increase in exercise duration (p = 0.001) for a 10 mg/24 hour dose. At 24 hours, however, the 29-second increase in exercise duration for a 10 mg/24 hour dose was not significant (p greater than 0.1), despite persistent decreases in systolic blood pressure, an increase in heart rate, and a "therapeutic" plasma nitroglycerin concentration. The findings indicate that the 10 mg/24 hour dose is not efficacious at 24 hours after application and support the hypothesis that nitroglycerin's effect on exercise performance is attenuated by nitrate tolerance even though hemodynamic effects and adequate blood levels persist.