Effect of timolol on mortality and reinfarction after acute myocardial infarction: Prognostic importance of heart rate at rest

Abstract

Long-term timolol treatment after acute myocardial infarction is associated with a significant reduction in mortality and nonfatal reinfarction. To evaluate whether the reduction in mortality and morbidity is exclusively or partly dependent on a reduction in heart rate (HR), cardiac events in the Norwegian Timolol Multicenter Study were analyzed according to resting HR at baseline and at 1 month of follow-up. Resting HR at baseline was a significant predictor of total death and all events (total death plus nonfatal reinfarction) both in placebo- and in timolol-treated patients. In the placebo group the median resting HR was unchanged from baseline to 1 month control (72 beats/min), but was reduced from 72 beats/min to 56 beats/min in the timolol group. Resting HR during follow-up remained a significant predictor of total death. Further, mortality at a given HR during treatment was not markedly different whether the HR was spontaneous or caused by timolol. Timolol treatment was related to a significant reduction in mortality, and this study suggests that the major effect of timolol treatment on mortality after acute myocardial infarction may be attributed to the reduction in HR. Timolol treatment was also associated with an overall reduction in nonfatal reinfarction. However, nonfatal reinfarction was inversely related to resting HR during follow-up, indicating that although coronary artery occlusion in low-risk patients may cause nonfatal reinfarction, the outcome in high-risk patients is more likely to be death. When analyzing mortality and nonfatal reinfarction combined, timolol treatment was related to a reduction in cardiac events at any given HR, suggesting that factors in addition to HR reduction are important in the protective effects of timolol.