Anticoagulation and Antiplatelet Therapy for Prevention of Venous and Arterial Thrombotic Events in Critically Ill Patients With COVID-19: COVID-PACT
Anticoagulation and Antiplatelet Therapy for Prevention of Venous and Arterial Thrombotic Events in Critically Ill Patients With COVID-19: COVID-PACT
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DOI：
10.1161/circulationaha.122.061533
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发表时间：
2022-11-01
期刊：
影响因子：
37.8
通讯作者：
Morrow, David A.
中科院分区：
文献类型：
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作者：
Bohula, Erin A.;Berg, David D.;Morrow, David A.
背景技术背景：COVID-19重症患者预防性全剂量抗凝和抗血小板治疗的有效性和安全性仍不确定。方法：COVID-PACT（预防重症COVID-19患者动静脉血栓形成事件试验）是一项多中心、2 × 2析因、开放标签、随机对照试验，在重症监护病房水平的COVID-19患者中进行盲法终点裁定。患者被随机分配至全剂量抗凝或标准剂量预防性抗凝治疗组。没有抗血小板治疗的适应症，患者被随机分配接受氯吡格雷或不接受抗血小板治疗。主要疗效结局是出院或28天内静脉或动脉血栓形成、肺栓塞、临床明显深静脉血栓形成、1型心肌梗死、缺血性卒中、全身性栓塞事件或急性肢体缺血或临床无症状深静脉血栓形成所致死亡的分层复合终点。主要疗效分析包括患者接受治疗时的不匹配胜率和首次事件发生时间分析。主要安全性结局为致死性或危及生命的出血。次要安全性结局为中度至重度出血。由于重症监护病房水平的COVID-19发病率下降，招募于2022年3月提前停止（约占计划招募的50%）。结果：在美国的34个中心，390名患者被随机分配到抗凝策略组，292名患者被随机分配到抗血小板策略组（治疗中分析为382名和290名）。在随机化时，99%的患者需要高级呼吸治疗，包括15%需要有创机械通气; 40%在住院期间需要有创通气。比较抗凝治疗策略，全剂量抗凝治疗（12.3%）与标准剂量预防性抗凝治疗（6.4%;获胜率，1.95 [95%CI，1.08-3.55]; P=0.028）的获胜比例更高。主要疗效终点的至事件发生时间分析结果一致（全剂量与标准剂量的发生率分别为19/191 [9.9%]与29/191 [15.2%];风险比为0.56 [95%CI，0.32-0.99]; P=0.046）。主要安全性终点发生在全剂量组4例（2.1%）和标准剂量组1例（0.5%）（P=0.19）;次要安全性终点发生在15例（7.9%）和1例（0.5%; P=0.002）。全因死亡率无差异（风险比，0.91 [95% CI，0.56-1.48]; P=0.70）。结论：在患有COVID-19的重症患者中，全剂量抗凝治疗（而非氯吡格雷）可减少血栓并发症，出血增加，主要由血流动力学稳定患者的输血驱动，死亡率无明显增加。
BACKGROUND: The efficacy and safety of prophylactic full-dose anticoagulation and antiplatelet therapy in critically ill COVID-19 patients remain uncertain.METHODS: COVID-PACT (Prevention of Arteriovenous Thrombotic Events in Critically-ill COVID-19 Patients Trial) was a multicenter, 2x2 factorial, open-label, randomized-controlled trial with blinded end point adjudication in intensive care unit-level patients with COVID-19. Patients were randomly assigned to a strategy of full-dose anticoagulation or standard-dose prophylactic anticoagulation. Absent an indication for antiplatelet therapy, patients were additionally randomly assigned to either clopidogrel or no antiplatelet therapy. The primary efficacy outcome was the hierarchical composite of death attributable to venous or arterial thrombosis, pulmonary embolism, clinically evident deep venous thrombosis, type 1 myocardial infarction, ischemic stroke, systemic embolic event or acute limb ischemia, or clinically silent deep venous thrombosis, through hospital discharge or 28 days. The primary efficacy analyses included an unmatched win ratio and time-to-first event analysis while patients were on treatment. The primary safety outcome was fatal or life-threatening bleeding. The secondary safety outcome was moderate to severe bleeding. Recruitment was stopped early in March 2022 (approximate to 50% planned recruitment) because of waning intensive care unit-level COVID-19 rates.RESULTS: At 34 centers in the United States, 390 patients were randomly assigned between anticoagulation strategies and 292 between antiplatelet strategies (382 and 290 in the on-treatment analyses). At randomization, 99% of patients required advanced respiratory therapy, including 15% requiring invasive mechanical ventilation; 40% required invasive ventilation during hospitalization. Comparing anticoagulation strategies, a greater proportion of wins occurred with full-dose anticoagulation (12.3%) versus standard-dose prophylactic anticoagulation (6.4%; win ratio, 1.95 [95% CI, 1.08-3.55]; P=0.028). Results were consistent in time-to-event analysis for the primary efficacy end point (full-dose versus standard-dose incidence 19/191 [9.9%] versus 29/191 [15.2%]; hazard ratio, 0.56 [95% CI, 0.32-0.99]; P=0.046). The primary safety end point occurred in 4 (2.1%) on full dose and in 1 (0.5%) on standard dose (P=0.19); the secondary safety end point occurred in 15 (7.9%) versus 1 (0.5%; P=0.002). There was no difference in all-cause mortality (hazard ratio, 0.91 [95% CI, 0.56-1.48]; P=0.70). There were no differences in the primary efficacy or safety end points with clopidogrel versus no antiplatelet therapy.CONCLUSIONS: In critically ill patients with COVID-19, full-dose anticoagulation, but not clopidogrel, reduced thrombotic complications with an increase in bleeding, driven primarily by transfusions in hemodynamically stable patients, and no apparent excess in mortality.