(PharmD for Pharmacists student), Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada, and St. Paul's Hospital, Lower Mainland Pharmacy Services, Vancouver, Canada.
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada, and Chilliwack General Hospital, Lower Mainland Pharmacy Services, Chilliwack, Canada.
Am J Health Syst Pharm. 2021 Nov 23;78(23):2132-2141. doi: 10.1093/ajhp/zxab226.
To identify randomized controlled trials that compared antiplatelet monotherapy to combination antiplatelet plus anticoagulant therapy and evaluated major adverse cardiovascular events (MACE) or major adverse limb events (MALE), death, or bleeding in patients with lower extremity peripheral artery disease (PAD).
A systematic search of MEDLINE, Embase, and CENTRAL databases revealed 5 trials. Two trials consisted of patients with stable PAD, while 3 trials examined patients with PAD post revascularization. Antiplatelet therapy was mostly aspirin (81-325 mg daily), and anticoagulation included rivaroxaban 2.5 mg twice daily or warfarin. Duration of follow-up ranged from 12 to 38 months. Two trials had low risk of bias, whereas 3 trials had high/unclear risk of bias. For patients with stable PAD, one trial showed that use of warfarin (or acenocoumarol) with antiplatelet therapy did not reduce MACE, MALE, or cardiovascular or all-cause death but increased the risk of life-threatening bleeding. A second trial demonstrated that low-dose rivaroxaban plus antiplatelet therapy lowered the risk of MACE and MALE, with no effect in preventing cardiovascular or all-cause death, but increased the risk of major bleeding. For patients with PAD post revascularization receiving warfarin and antiplatelet therapy, 2 trials showed no benefit in MACE or MALE but increased or similar rates of all-cause death and major bleeding. In a third trial, low-dose rivaroxaban plus aspirin reduced occurrence of the composite of MACE and MALE but increased major bleeding, with no effect on cardiovascular or all-cause death.
Dual-pathway inhibition with low-dose rivaroxaban and aspirin reduced MACE and MALE in patients with stable or revascularized PAD, but net clinical benefit is questionable.
确定比较抗血小板单药治疗与联合抗血小板加抗凝治疗，并评估下肢外周动脉疾病（PAD）患者主要不良心血管事件（MACE）或主要不良肢体事件（MALE）、死亡或出血的随机对照试验。
系统检索 MEDLINE、Embase 和 CENTRAL 数据库共发现 5 项试验。其中 2 项试验纳入稳定型 PAD 患者，3 项试验纳入 PAD 血运重建后患者。抗血小板治疗主要为阿司匹林（81-325mg 每日），抗凝治疗包括利伐沙班 2.5mg 每日 2 次或华法林。随访时间为 12-38 个月。其中 2 项试验的偏倚风险较低，3 项试验的偏倚风险较高/不明确。对于稳定型 PAD 患者，一项试验表明，华法林（或醋硝香豆素）联合抗血小板治疗并未降低 MACE、MALE、心血管或全因死亡风险，但增加了致命性出血风险。第二项试验表明，低剂量利伐沙班联合抗血小板治疗降低了 MACE 和 MALE 风险，对预防心血管或全因死亡无影响，但增加了大出血风险。对于接受华法林和抗血小板治疗的 PAD 血运重建后患者，2 项试验显示 MACE 或 MALE 无获益，但全因死亡和大出血发生率增加或相似。在第 3 项试验中，低剂量利伐沙班加阿司匹林降低了 MACE 和 MALE 复合终点的发生，但增加了大出血，对心血管或全因死亡无影响。
低剂量利伐沙班联合阿司匹林抑制双重途径可减少稳定型或血运重建型 PAD 患者的 MACE 和 MALE，但净临床获益值得怀疑。
