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A multicenter study on timolol in secondary prevention after myocardial infarction
Insights
Long-term timolol treatment significantly improved survival for patients after myocardial infarction. This beta-blocker reduced overall mortality and sudden cardiac death in study participants.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Patients surviving myocardial infarction face high long-term mortality.
- This mortality is primarily due to sudden cardiac death and recurrent myocardial infarction.
Purpose of the Study:
- To determine if long-term timolol treatment improves prognosis in myocardial infarction survivors.
- To assess the impact of timolol on reducing mortality and sudden cardiac death.
Main Methods:
- A randomized, double-blind, placebo-controlled multicenter trial involving 1884 patients.
- Patients were stratified into three risk groups and followed for 12-33 months.
- Timolol and placebo groups were compared using statistical analyses, including Cox's proportional hazards regression.
Main Results:
- Timolol treatment resulted in a statistically significant 39.3% reduction in mortality compared to placebo (13.3% vs. 21.9%).
- A significant decrease in sudden cardiac death was observed in the timolol group (7.7% vs. 13.9%).
- High patient compliance and low loss to follow-up ensured study validity.
Conclusions:
- Long-term timolol treatment offers significant prognostic benefits for survivors of acute myocardial infarction.
- Timolol effectively reduces mortality, particularly sudden cardiac death, in this patient population.
Abstract:
Patients who survive the acute phase of myocardial infarction have a high mortality in the following years. The mortality is largely due to sudden cardiac death or recurrent myocardial infarction. The main purpose of the present study was to clarify whether long-term treatment with the beta-adrenergic blocking agent timolol would improve prognosis in such patients. In order to recruit the sufficient number of patients to resolve this question a multicenter study was performed. This study, named "The Norwegian Multicenter Study On Timolol After Myocardial Infarction" was designed as a randomized, double-blind, placebo controlled trial. Twenty hospitals in Norway collaborated within an organizational structure aiming to achieve a maximum of standardization of study procedures. From a representative population of patients less than 75 years of age surviving the acute episode of infarction 52% were recruited for the study. The recruitment rate was high at all hospitals. The 1884 patients included were stratified into 3 risk groups before randomization. Risk Group I (18%) were patients with a recurrent infarction. Risk Group II (58%) were patients with a first infarction considered to be at high risk of sudden cardiac death. The rest, Risk Group III (22%) were patients at low risk. The placebo and timolol groups were similar with respect to most of the important baseline characteristics. Minor differences in a few characteristics did not affect the overall results as was shown by various statistical procedures including the Cox's proportional hazards regression model. The patients were followed 12 - 33 months after discharge from hospital with regular clinical examinations performed by the study investigators at the hospitals. Compliance was very good and no patient was lost to follow-up although 23.3% in the placebo group and 29.1% in the timolol group were withdrawn from the study regimen. The study demonstrated that long-term treatment with timolol improved prognosis in survivors of acute myocardial infarction. The most important finding was a highly statistically significant difference in life table mortality of 39.3% between the placebo group (21.9%) and the timolol group (13.3%) (p=0.0003). This difference was first of all due to a lower rate of sudden cardiac death in the timolol group (7.7%) compared to the placebo group (13.9%) (p=0.0001) when including events in the so-called "per protocol period".(ABSTRACT TRUNCATED AT 400 WORDS)