Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina (T.Y.W., A.P.).
Departments of Biostatistics, Epidemiology, and Statistics, University of Pittsburgh, Pittsburgh, Pennsylvania (A.S.W.).
Ann Intern Med. 2023 Apr;176(4):515-523. doi: 10.7326/M22-3350. Epub 2023 Mar 21.
Patients hospitalized with COVID-19 have an increased incidence of thromboembolism. The role of extended thromboprophylaxis after hospital discharge is unclear.
To determine whether anticoagulation is superior to placebo in reducing death and thromboembolic complications among patients discharged after COVID-19 hospitalization.
Prospective, randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT04650087).
Done during 2021 to 2022 among 127 U.S. hospitals.
Adults aged 18 years or older hospitalized with COVID-19 for 48 hours or more and ready for discharge, excluding those with a requirement for, or contraindication to, anticoagulation.
2.5 mg of apixaban versus placebo twice daily for 30 days.
The primary efficacy end point was a 30-day composite of death, arterial thromboembolism, and venous thromboembolism. The primary safety end points were 30-day major bleeding and clinically relevant nonmajor bleeding.
Enrollment was terminated early, after 1217 participants were randomly assigned, because of a lower than anticipated event rate and a declining rate of COVID-19 hospitalizations. Median age was 54 years, 50.4% were women, 26.5% were Black, and 16.7% were Hispanic; 30.7% had a World Health Organization severity score of 5 or greater, and 11.0% had an International Medical Prevention Registry on Venous Thromboembolism risk prediction score of greater than 4. Incidence of the primary end point was 2.13% (95% CI, 1.14 to 3.62) in the apixaban group and 2.31% (CI, 1.27 to 3.84) in the placebo group. Major bleeding occurred in 2 (0.4%) and 1 (0.2%) and clinically relevant nonmajor bleeding occurred in 3 (0.6%) and 6 (1.1%) apixaban-treated and placebo-treated participants, respectively. By day 30, thirty-six (3.0%) participants were lost to follow-up, and 8.5% of apixaban and 11.9% of placebo participants permanently discontinued the study drug treatment.
The introduction of SARS-CoV-2 vaccines decreased the risk for hospitalization and death. Study enrollment spanned the peaks of the Delta and Omicron variants in the United States, which influenced illness severity.
The incidence of death or thromboembolism was low in this cohort of patients discharged after hospitalization with COVID-19. Because of early enrollment termination, the results were imprecise and the study was inconclusive.
National Institutes of Health.
COVID-19 住院患者发生血栓栓塞的几率增加。出院后延长血栓预防的作用尚不清楚。
确定抗凝治疗是否优于安慰剂，以降低 COVID-19 住院后出院患者的死亡和血栓栓塞并发症的发生率。
前瞻性、随机、双盲、安慰剂对照临床试验。（ClinicalTrials.gov：NCT04650087）。
2021 年至 2022 年期间在美国 127 家医院进行。
年龄在 18 岁或以上，因 COVID-19 住院 48 小时或以上且准备出院的成年人，不包括需要或禁忌抗凝的患者。
每天两次给予 2.5 毫克阿哌沙班与安慰剂，持续 30 天。
主要疗效终点为 30 天内死亡、动脉血栓栓塞和静脉血栓栓塞的复合终点。主要安全性终点为 30 天内大出血和临床相关非大出血。
由于预计事件发生率较低且 COVID-19 住院率下降，在 1217 名参与者随机分配后提前终止了入组。中位年龄为 54 岁，50.4%为女性，26.5%为黑人，16.7%为西班牙裔；30.7%的患者世界卫生组织严重程度评分为 5 分或以上，11.0%的患者国际静脉血栓栓塞预防注册的风险预测评分大于 4 分。阿哌沙班组的主要终点发生率为 2.13%（95%CI，1.14 至 3.62），安慰剂组为 2.31%（CI，1.27 至 3.84）。大出血分别发生在 2 名（0.4%）和 1 名（0.2%）阿哌沙班组和安慰剂组参与者中，临床相关非大出血分别发生在 3 名（0.6%）和 6 名（1.1%）阿哌沙班组和安慰剂组参与者中。在第 30 天，有 36 名（3.0%）参与者失访，阿哌沙班组和安慰剂组分别有 8.5%和 11.9%的参与者永久性停止了研究药物治疗。
SARS-CoV-2 疫苗的推出降低了住院和死亡的风险。研究入组横跨了美国 Delta 和 Omicron 变体的高峰期，这影响了疾病的严重程度。
在 COVID-19 住院后出院的患者中，死亡或血栓栓塞的发生率较低。由于提前终止入组，结果不够精确，研究结果不确定。
美国国立卫生研究院。
