Similar risk reduction of death of extended-release metoprolol once daily and immediate-release metoprolol twice daily during 5 years after myocardial infarction

The pooled results from five placebo-controlled postinfarction studies with metoprolol have shown a significant reduction in total mortality. All five studies used immediate-release metoprolol twice daily. An extended-release formulation of metoprolol for once-daily use has since been developed. The aim of the present study was to compare the two different forms of metopro lol with regard to the risk reduction of death for 5 years postinfarction a nd to analyze whether treatment with the beta-blocker metoprolol is associa ted with a reduced mortality after the introduction of modern therapies suc h as thrombolysis, aspirin, and ACE inhibitors. All patients discharged aft er an acute myocardial infarction (AMI) from Sahlgrenska University Hospita l (SU) during 1986-1987 (n = 740, Period I) and during 1990-1991 (n = 1446, Period II) from both SU and Ostra Hospital, Goteborg, Sweden, were include d in the study during Period I, 56% were prescribed immediate-release metop rolol compared with 61% prescribed extended-release metoprolol during Perio d II. Immediate-release metoprolol was not available for outpatient use dur ing Period II. In a multivariate analysis, all variables significantly asso ciated with either increased or decreased postinfarction mortality during P eriods I and II (univariate analysis of patient characteristics, medical hi story, complications during the AMI medication at discharge) studied were w ith Cox's proportional hazards model. Treatment with immediate-release meto prolol was significantly associated with reduced mortality over 5 years dur ing Period I (relative risk reduction for total mortality, -34%, P = 0.003; 95% CI for RR, 0.51-0.87), and treatment with extended-release metoprolol was significantly associated with reduced mortality during Period II (-34%, P < 0.0001; 95% CI for RR, 0.53-0.82). Thrombolysis and the use of aspirin and ACE inhibitors were more frequently used during Period II. The results showed that postinfarction treatment with extended-release metoprolol give n once daily was associated with a similar risk reduction of death over 5 y ears as immediate-release metoprolol given twice daily. The data, furthermo re, indicate that the beta-blocker metoprolol is associated with a reduced risk of death after the introduction of modern therapy such as thrombolysis , aspirin, and ACE inhibitors.