BACKGROUND Ticagrelor reduces ischemic risk in patients with prior myocardial infarction (MI). It remains unclear whether ischemic risk and the benefits of prolonged P2Y12 inhibition in this population remain consistent over time. OBJECTIVES The study sought to investigate the pattern of ischemic risk over time and whether the efficacy and safety of ticagrelor were similar early and late after randomization. METHODS The PEGASUS-TIMI (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis In Myocardial Infarction) 54 trial randomized patients with prior MI (median 1.7 years prior) to ticagrelor 90 mg, ticagrelor 60 mg, or placebo on a background of aspirin. The rates of cardiovascular (CV) death, MI, and stroke as well as TIMI major bleeding were analyzed at yearly landmarks (years 1, 2, and 3). RESULTS A total of 21,162 patients were randomized and followed for 33 months (median), with 28% of patients ≥5 years from MI at trial conclusion. The risk of CV death, MI, or stroke in the placebo arm remained roughly constant over the trial at an ∼3% annualized rate. The benefit of ticagrelor 60 mg was consistent at each subsequent landmark (year 1 hazard ratio [HR]: 0.82; 95% confidence interval [CI]: 0.67 to 0.99; year 2 HR: 0.90; 95% CI: 0.74 to 1.11; and year 3 HR: 0.79; 95% CI: 0.62 to 1.00). TIMI major bleeding was increased with ticagrelor 60 mg at each landmark, but with the greatest hazard in the first year (year 1 HR: 3.22; year 2 HR: 2.07; year 3 HR: 1.65). CONCLUSIONS Patients with a history of MI remain at persistent high risk for CVD, MI, and stroke as late as 5 years after MI. The efficacy of low-dose ticagrelor is consistent over time with a trend toward less excess bleeding. (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562).

中文翻译：

---

在 PEGASUS-TIMI 54 中替格瑞洛治疗既往 MI 患者随时间推移的疗效和安全性

背景替格瑞洛降低了既往心肌梗死 (MI) 患者的缺血风险。目前尚不清楚该人群的缺血风险和长期 P2Y12 抑制的益处是否随着时间的推移保持一致。目的 本研究旨在调查随时间推移的缺血风险模式，以及随机化后早期和晚期替格瑞洛的疗效和安全性是否相似。方法 PEGASUS-TIMI（在心肌梗死阿司匹林溶栓背景下使用替格瑞洛与安慰剂相比预防既往心脏病发作患者的心血管事件）54 项试验将既往心肌梗死患者（中位时间为 1.7 年前）随机分配至替格瑞洛 90 mg，替格瑞洛 60 毫克，或以阿司匹林为背景的安慰剂。心血管 (CV) 死亡率、MI、在每年的里程碑（第 1、2 和 3 年）分析中风和 TIMI 大出血。结果 共有 21,162 名患者被随机分组​​并随访了 33 个月（中位数），其中 28% 的患者在试验结束时发生 MI ≥ 5 年。安慰剂组的 CV 死亡、MI 或中风风险在整个试验期间大致保持不变，年化率约为 3%。替格瑞洛 60 mg 的益处在随后的每个里程碑上都是一致的（第 1 年风险比 [HR]：0.82；95% 置信区间 [CI]：0.67 至 0.99；第 2 年 HR：0.90；95% CI：0.74 至 1.11；和第 3 年 HR：0.79；95% CI：0.62 至 1.00）。TIMI 大出血在每个标志物 60 mg 替格瑞洛时增加，但在第一年危害最大（第 1 年 HR：3.22；第 2 年 HR：2.07；第 3 年 HR：1.65）。结论 有 MI 病史的患者仍处于持续的 CVD 高风险中，MI 和最迟在 MI 后 5 年发生中风。随着时间的推移，低剂量替格瑞洛的疗效与出血量减少的趋势一致。（与阿司匹林[飞马] 背景下的安慰剂相比，使用替格瑞洛预防既往心脏病发作患者的心血管事件；NCT01225562）。