Vale Claire L, Godolphin Peter J, Fisher David J, Higgins Julian P T, McAleenan Alexandra, Spiga Francesca, Tritschler Tobias, de Barros E Silva Pedro Gabriel Melo, Berg David D, Berger Jeffrey S, Berry Lindsay R, Bikdeli Behnood, Blondon Marc, Bohula Erin A, Cattaneo Marco, Colombo Riccardo, Coluccio Valeria, DeSancho Maria T, Farkouh Michael E, Fuster Valentin, Girardis Massimo, Hochman Judith S, Jensen Thomas P, Jha Vivekanand, Jüni Peter, Kirtane Ajay J, Lawler Patrick, Le Gal Grégoire, Lecumberri Ramon, Lentz Steven R, Lopes Renato D, Lorenzi Elizabeth, Marietta Marco, Miranda Carlos Henrique, Morici Nuccia, Morpeth Susan C, Morrow David A, McQuilten Zoe K, Muñoz-Rivas Nuria, Neal Matthew D, Pant Suman, Parikh Sahil A, Perepu Usha, Sadeghipour Parham, Sethi Sanjum, Sholzberg Michelle, Spyropoulos Alex C, Stone Gregg W, Talasaz Azita Hajhossein, Tong Steven, Totterdell James, Venkatesh Balasubramanian, Wu Maddalena Alessandra, Zarychanski Ryan, Zuily Stephane, Viry Julie, Rylance Jamie, Adhikari Neill K J, Diaz Janet V, Marshall John C, Sterne Jonathan A C, Murthy Srinivas
Ann Intern Med. 2025 Jan;178(1):59-69. doi: 10.7326/ANNALS-24-00800. Epub 2024 Dec 24.
Reported results of clinical trials assessing higher-dose anticoagulation in patients hospitalized for COVID-19 have been inconsistent.
To estimate the association of higher- versus lower-dose anticoagulation with clinical outcomes.
Randomized trials were identified from the World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials.gov with no restriction by trial status or language.
Eligible randomized trials assigned patients hospitalized for COVID-19 to higher- versus lower-dose anticoagulation.
20 eligible trials provided data in a prospectively agreed format. Two further studies were included based on published data. The primary outcome was all-cause mortality 28 days after randomization. Secondary outcomes were progression to invasive mechanical ventilation or death, thromboembolic events, and major bleeding.
Therapeutic- compared with prophylactic-dose anticoagulation with heparins reduced 28-day mortality (OR, 0.77 [95% CI, 0.64 to 0.93]; = 29%; 11 trials, 6297 patients, of whom 5456 required low or no oxygen at randomization). The ORs for 28-day mortality were 1.21 (CI, 0.93 to 1.58; = 0%) for therapeutic-dose compared with intermediate-dose anticoagulation (6 trials, 1803 patients, 843 receiving noninvasive ventilation at randomization) and 0.95 (CI, 0.76 to 1.19; = 0%; 10 trials, 3897 patients, 2935 receiving no or low oxygen at randomization) for intermediate- versus prophylactic-dose anticoagulation. Treatment effects appeared broadly consistent across predefined patient subgroups, although some analyses were limited in power. Higher- compared with lower-dose anticoagulation was associated with fewer thromboembolic events, but a greater risk for major bleeding.
Therapeutic-dose compared with prophylactic-dose anticoagulation reduced 28-day mortality. Mortality was similar for intermediate-dose compared with prophylactic-dose anticoagulation and higher for therapeutic-dose compared with intermediate-dose anticoagulation, although this comparison was not estimated precisely.
No direct funding. (PROSPERO: CRD42020213461).
评估新冠病毒疾病（COVID-19）住院患者高剂量抗凝治疗的临床试验报告结果并不一致。
评估高剂量与低剂量抗凝治疗与临床结局之间的关联。
从世界卫生组织国际临床试验注册平台和美国国立医学图书馆临床试验数据库中检索随机对照试验，不受试验状态或语言限制。
符合条件的随机对照试验将COVID-19住院患者随机分为高剂量抗凝组和低剂量抗凝组。
20项符合条件的试验以前瞻性商定的格式提供数据。根据已发表的数据纳入另外两项研究。主要结局是随机分组后28天的全因死亡率。次要结局是进展为有创机械通气或死亡、血栓栓塞事件和大出血。
与肝素预防性剂量抗凝相比，治疗性剂量抗凝降低了28天死亡率（比值比[OR]，0.77[95%置信区间（CI），0.64至0.93]；P=29%；11项试验，6297例患者，其中5456例随机分组时需要低流量吸氧或无需吸氧）。与中等剂量抗凝相比，治疗性剂量抗凝的28天死亡率OR为1.21（CI，0.93至1.58；P=0%；6项试验，1803例患者，843例随机分组时接受无创通气），中等剂量与预防性剂量抗凝相比，28天死亡率OR为0.95（CI，0.76至1.19；P=0%；10项试验，3897例患者，2935例随机分组时接受无或低流量吸氧）。尽管一些分析的检验效能有限，但在预先定义的患者亚组中，治疗效果总体上是一致的。与低剂量抗凝相比，高剂量抗凝与较少的血栓栓塞事件相关，但大出血风险更高。
与预防性剂量抗凝相比，治疗性剂量抗凝降低了28天死亡率。中等剂量与预防性剂量抗凝相比，死亡率相似；治疗性剂量与中等剂量抗凝相比，死亡率更高，尽管这种比较的估计并不精确。
无直接资金。（国际前瞻性系统评价注册库：CRD42020213461）
