TIMI Study Group, Brigham and Women's Hospital, Heart & Vascular Center, 75 Francis Street, Boston, MA 02115, USA
TIMI Study Group, Brigham and Women's Hospital, Heart & Vascular Center, 75 Francis Street, Boston, MA 02115, USA.
Eur Heart J. 2016 Apr 7;37(14):1133-42. doi: 10.1093/eurheartj/ehv531. Epub 2015 Oct 21.
AIMS: Ticagrelor reduced major adverse cardiovascular event (MACE) by 15-16% in patients with prior myocardial infarction (MI) in PEGASUS-TIMI 54. We hypothesized that patients who recently discontinued P2Y12 inhibition, even years after MI, may be at particular risk of MACE and may derive particular benefit from continuation or reinitiation of therapy. METHODS AND RESULTS: Patients in PEGASUS-TIMI 54 were categorized by time from last P2Y12 inhibitor (days: ≤30, >30-360, >360). The risk of MACE and the efficacy of ticagrelor were compared across categories. In the placebo arm, patients who more recently stopped P2Y12 inhibitor therapy had a greater number of risk factors but still had a higher risk of MACE after multivariable adjustment [≤30 days, hazard ratio (HR)adj 1.47, 95% confidence interval (CI) 1.12-1.93, P = 0.0051; 30 days-1 year, HRadj 1.28, 95% CI 0.98-1.67, P = 0.073] compared with those who stopped >1 year prior (P-trend = 0.0097). The benefit of ticagrelor depended on the time from last dose, with HRs (95% CI) for ticagrelor (pooled doses) vs. placebo of 0.73 (0.61-0.87), 0.86 (0.71-1.04), and 1.01 (0.80-1.27), respectively, by category (P-trend for interaction < 0.001). The benefit in those ≤30 days of stopping was similar regardless of time from MI (<2 years, HR 0.73, 95% CI 0.60-0.89 vs. ≥2 years, HR 0.71, 95% CI 0.50-1.00). CONCLUSION: The benefit of ticagrelor for long-term secondary prevention in patients with prior MI and at least one additional risk factor appeared more marked in patients continuing on or re-starting after only a brief interruption of P2Y12 inhibition, when compared with patients who had proved themselves stable more than 2 years from their MI and off P2Y12 inhibitor therapy for more than a year. The increase in bleeding events with ticagrelor was similar regardless of this time interval. For clinicians considering a strategy of prolonged P2Y12 inhibitor therapy in high-risk patients, these data suggest greater benefit in the continuation of such therapy without interruption after MI, rather than re-initiating such therapy in patients who have remained stable for an extended period. Future analyses may help to clarify further the profile of post-MI patients most likely to benefit from uninterrupted dual antiplatelet therapy. CLINICAL TRIAL REGISTRATION INFORMATION: http://www.clinicaltrials.gov NCT01225562.
目的：替格瑞洛可使既往发生心肌梗死（MI）的患者主要不良心血管事件（MACE）减少 15-16%。我们假设，即使在 MI 发生多年后，最近停止 P2Y12 抑制剂治疗的患者可能特别容易发生 MACE，并且可能特别受益于继续或重新开始治疗。
方法和结果：在 PEGASUS-TIMI 54 中，根据患者最后一次使用 P2Y12 抑制剂的时间（天：≤30、>30-360、>360）对患者进行分类。比较了各个分类中 MACE 的风险和替格瑞洛的疗效。在安慰剂组中，与停药超过 1 年的患者相比，近期停止 P2Y12 抑制剂治疗的患者有更多的危险因素，但多变量调整后 MACE 风险仍然更高[≤30 天，风险比（HR）adj 1.47，95%置信区间（CI）1.12-1.93，P=0.0051；30 天-1 年，HRadj 1.28，95%CI 0.98-1.67，P=0.073]（P趋势=0.0097）。替格瑞洛的获益取决于最后一剂的时间，替格瑞洛（累积剂量）与安慰剂相比的 HR（95%CI）分别为 0.73（0.61-0.87）、0.86（0.71-1.04）和 1.01（0.80-1.27），按类别分组（交互作用 P 趋势<0.001）。停药 ≤30 天的获益与 MI 发生后的时间无关（<2 年，HR 0.73，95%CI 0.60-0.89 vs. ≥2 年，HR 0.71，95%CI 0.50-1.00）。
结论：在既往发生 MI 且至少有一个额外危险因素的患者中，替格瑞洛用于长期二级预防的获益似乎在停药后不久继续或重新开始使用替格瑞洛的患者中更为明显，而在 MI 后超过 2 年且停用 P2Y12 抑制剂治疗超过 1 年的患者中则不明显。替格瑞洛引起的出血事件增加与这一时间间隔无关。对于考虑对高危患者进行长期 P2Y12 抑制剂治疗策略的临床医生来说，这些数据表明，在 MI 后继续不间断地进行此类治疗而不中断，比在已经稳定一段时间的患者中重新开始此类治疗更有获益。未来的分析可能有助于进一步阐明最有可能从不间断双联抗血小板治疗中获益的 MI 后患者的特征。
临床试验注册信息：http://www.clinicaltrials.gov NCT01225562。
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