Gundersen T, Grøttum P, Pedersen T, Kjekshus J K
Am J Cardiol. 1986 Jul 1;58(1):20-4. doi: 10.1016/0002-9149(86)90234-1.
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.
急性心肌梗死后长期使用噻吗洛尔治疗与死亡率和非致命性再梗死的显著降低相关。为了评估死亡率和发病率的降低是完全还是部分取决于心率（HR）的降低，根据基线时和随访1个月时的静息心率，对挪威噻吗洛尔多中心研究中的心脏事件进行了分析。基线时的静息心率是安慰剂组和噻吗洛尔治疗组中全因死亡和所有事件（全因死亡加非致命性再梗死）的显著预测因素。在安慰剂组中，静息心率从基线到1个月的对照期未发生变化（72次/分钟），但在噻吗洛尔组中从72次/分钟降至56次/分钟。随访期间的静息心率仍然是全因死亡的显著预测因素。此外，无论心率是自发的还是由噻吗洛尔引起的，治疗期间给定心率下的死亡率并无明显差异。噻吗洛尔治疗与死亡率的显著降低相关，并且这项研究表明，噻吗洛尔治疗对急性心肌梗死后死亡率的主要影响可能归因于心率的降低。噻吗洛尔治疗还与非致命性再梗死的总体减少相关。然而，非致命性再梗死与随访期间的静息心率呈负相关，这表明尽管低风险患者的冠状动脉闭塞可能导致非致命性再梗死，但高风险患者的结局更可能是死亡。在分析死亡率和非致命性再梗死合并情况时，噻吗洛尔治疗与任何给定心率下心脏事件的减少相关，这表明除心率降低外的其他因素在噻吗洛尔产生保护作用方面也很重要。
