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In a multicenter double-blind study, 227 patients with suspected acute myocardial infarction (AMI) were randomized within 12 hr from onset of symptoms to treatment with nifedipine (112 patients) or placebo (115 patients). AMI was confirmed in 74 patients on nifedipine and in 83 on placebo. Patients with AMI received nifedipine 5.5 +/- 2.9 hr (mean +/- SD) after onset of symptoms. Infarct size was assessed by the release of creatine kinase isoenzyme MB (CK-MB). Infarct size index (CK-MB geq/m2) was 25 +/- 16 (n = 71) in the nifedipine group and 23 +/- 13 (n = 77) in the placebo group (NS). After the first 10 mg of nifedipine systolic blood pressure fell from 147 +/- 30 to 135 +/- 28 mm Hg (p less than .01) and heart rate rose from 75 +/- 18 to 79 +/- 19 beats/min (p less than .01). No change was observed after the first placebo dose. The treatment was continued for 6 weeks. Over this period there were 10 deaths in each group. Early treatment with nifedipine in patients with AMI does not seem to reduce infarct size as determined by enzyme level.

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.

The influence of long-term timolol treatment on plasma lipids was analysed in cohorts of the Norwegian timolol multicentre study. The prognostic importance of high-density lipoprotein (HDL) cholesterol concentration after myocardial infarction was also examined. One year timolol treatment was related to a significant reduction in HDL cholesterol levels, from 1.32 mmol l-1 to 1.26 mmol l-1 (P less than 0.05). After one year the HDL cholesterol levels were significantly lower in the timolol treated patients (1.26 mmol l-1) than in the placebo treated patients (1.32 mmol l-1, P less than 0.01). However, the HDL cholesterol values after myocardial infarction had no prognostic importance, and in the placebo group total mortality was the same in patients with low HDL cholesterol (less than 1.25 mmol l-1) and high HDL cholesterol (greater than or equal to 1.25 mmol l-1), respectively 15.0% and 14.8%. Timolol treatment was related to a reduction in mortality both in patients with low (24%, NS) and with high (43%, P less than 0.05) HDL cholesterol levels. Thus, any deleterious effects of timolol on serum lipids did not attenuate its protective effect on the damaged myocardium.

The original Norwegian Multicenter Study on Timolol after Myocardial Infarction was a double-blind, randomized study comparing the effect of timolol with that of placebo for up to 33 months after acute myocardial infarction. The initial results showed that the cumulated mortality rate was 39.4 per cent lower among 945 patients randomly assigned to timolol treatment than among 939 patients randomly assigned to placebo (P = 0.0003). After the end of the double-blind period the majority of participating patients in the timolol group continued to receive beta-adrenergic blockade, whereas the majority of placebo-treated patients continued without such blockade. During an extended follow-up of participating patients up to 72 months after randomization, the mortality curves of the two groups continued to rise in parallel. Cumulated mortality rates were 32.3 per cent in the placebo group and 26.4 per cent in the timolol group (P = 0.0028). We conclude that the previously observed early beneficial effect of beta-adrenergic blocking therapy is maintained for at least six years after infarction.