Cardiovascular Division Department of Medicine Stony Brook University Medical Center Stony Brook NY.
Cardiovascular Division Department of Medicine TIMI Study GroupBrigham and Women's Hospital and Harvard Medical School Boston MA.
J Am Heart Assoc. 2021 Oct 19;10(20):e021412. doi: 10.1161/JAHA.121.021412. Epub 2021 Oct 8.
Background Patients with peripheral artery disease are at increased risk of both major adverse cardiovascular events (MACEs) and limb events. The pathobiology of limb events is likely multifactorial. Observational studies suggest a benefit of statin therapy for reducing the risk of limb ischemic events while randomized trials demonstrate a benefit with more potent antithrombotic therapies, particularly those targeting thrombin. Whether the effects of these therapeutic pathways are independent and complementary is not known. Methods and Results The TRA 2°P-TIMI 50 (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-Thrombolysis in Myocardial Infarction 50) trial demonstrated that vorapaxar significantly reduced MACEs and limb events. The purpose of the current analysis was to evaluate the association of statin use and intensity and the occurrence of MACEs and limb events in 5845 patients with symptomatic peripheral artery disease randomized in TRA 2°P-TIMI 50 and then to understand whether statin use modified the benefits of vorapaxar for MACEs or limb ischemic events. We found that statin therapy was associated with significantly lower risk of MACEs (hazard ratio [HR], 0.77; 95% CI, 0.66-0.89; <0.001) and limb ischemic events (HR, 0.73; 95% CI, 0.60-0.89; =0.002). The benefit of vorapaxar for reducing MACEs and limb events was consistent regardless of background statin (-interaction=0.715 and 0.073, respectively). Event rates were lowest in patients receiving the combination of statin therapy and vorapaxar. Conclusions In conclusion, statin use and intensity is associated with significantly lower rates of MACEs and limb ischemic events. Thrombin inhibition with vorapaxar is effective regardless of background statin therapy. These results suggest that targeting both lipid and thrombotic risk in peripheral artery disease is necessary in order to optimize outcomes.
外周动脉疾病患者发生主要不良心血管事件（MACEs）和肢体事件的风险均增加。肢体事件的病理生理学可能是多因素的。观察性研究表明他汀类药物治疗可降低肢体缺血性事件的风险，而随机试验则表明更有效的抗血栓治疗（特别是针对凝血酶的治疗）具有益处。这些治疗途径的效果是否独立和互补尚不清楚。
TRA 2°P-TIMI 50（血栓素受体拮抗剂在动脉粥样硬化血栓缺血性事件二级预防-心肌梗死溶栓 50）试验表明，沃拉帕沙显著降低了 MACEs 和肢体事件。本分析的目的是评估 5845 例有症状外周动脉疾病患者在 TRA 2°P-TIMI 50 中随机分组后他汀类药物使用和强度与 MACEs 和肢体事件发生的相关性，然后了解他汀类药物的使用是否改变了沃拉帕沙对 MACEs 或肢体缺血性事件的益处。我们发现，他汀类药物治疗与 MACEs（风险比[HR]，0.77；95%置信区间[CI]，0.66-0.89；<0.001）和肢体缺血性事件（HR，0.73；95%CI，0.60-0.89；=0.002）的风险显著降低相关。无论背景他汀类药物如何，沃拉帕沙降低 MACEs 和肢体事件的益处都是一致的（-交互作用分别为 0.715 和 0.073）。接受他汀类药物治疗和沃拉帕沙联合治疗的患者事件发生率最低。
他汀类药物的使用和强度与 MACEs 和肢体缺血性事件的发生率显著降低相关。沃拉帕沙抑制凝血酶的作用与背景他汀类药物治疗无关。这些结果表明，为了优化结局，在外周动脉疾病中靶向脂质和血栓形成风险是必要的。
