Meta-Analysis of Reversal Agents for Severe Bleeding Associated With Direct Oral Anticoagulants

被引:93
作者
Gomez-Outes, Antonio [1 ]
Alcubilla, Pau [2 ]
Calvo-Rojas, Gonzalo [2 ,3 ]
Terleira-Fernandez, Ana Isabel [4 ,5 ]
Suarez-Gea, Luisa [1 ]
Lecumberri, Ramon [6 ,7 ]
Vargas-Castrillon, Emilio [4 ,5 ]
机构
[1] Spanish Agcy Med & Med Devices AEMPS, Div Pharmacol & Clin Drug Evaluat, Madrid, Spain
[2] Hosp Clin Barcelona, Dept Clin Pharmacol, Barcelona, Spain
[3] Univ Barcelona, Barcelona, Spain
[4] Hosp Clinico San Carlos, Dept Clin Pharmacol, IdISSC, Madrid, Spain
[5] Univ Complutense, Dept Pharmacol, IdISSC, Madrid, Spain
[6] Univ Clin Navarra, Hematol Serv, Pamplona, Spain
[7] Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Cardiovasc CIB, Madrid, Spain
关键词
PROTHROMBIN COMPLEX CONCENTRATE; ATRIAL-FIBRILLATION; INTRACRANIAL HEMORRHAGE; DABIGATRAN REVERSAL; ANDEXANET ALPHA; IDARUCIZUMAB; MANAGEMENT; WARFARIN; RIVAROXABAN; SAFETY;
D O I
10.1016/j.jacc.2021.04.061
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUND Direct oral anticoagulants (DOACs) have shown a positive benefit-risk balance in both clinical trials and real-world data, but approximately 2% to 3.5% of patients experience major bleeding annually. Many of these patients require hospitalization, and the administration of reversal agents may be required to control bleeding. OBJECTIVES The aim of this study was to investigate clinical outcomes associated with the use of 4-factor pro thrombin complex concentrates, idarucizumab, or andexanet for reversal of severe DOAC-associated bleeding. METHODS The investigators systematically searched for studies of reversal agents for the treatment of severe bleeding associated with DOAC. Mortality rates, thromboembolic events, and hemostatic efficacy were meta-analyzed using a random effects model. RESULTS The investigators evaluated 60 studies in 4,735 patients with severe DOAC-related bleeding who were treated with 4-factor prothrombin complex concentrates (n = 2,688), idarucizumab (n = 1,111), or andexanet (n = 936). The mortality rate was 17.7% (95% confidence interval [CI]: 15.1% to 20.4%), and it was higher in patients with intracranial bleedings (20.2%) than in patients with extracranial hemorrhages (15.4%). The thromboembolism rate was 4.6% (95% CI: 3.3% to 6.0%), being particularly high with andexanet (10.7%; 95% CI: 6.5% to 15.7%). The effective hemostasis rate was 78.5% (95% CI: 75.1% to 81.8%) and was similar regardless of the reversal agent considered. The rebleeding rate was 13.2% (95% CI: 5.5% to 23.1%) and 78% of rebleeds occurred after resumption of anticoagulation. The risk of death was markedly and significantly associated with failure to achieve effective hemostasis (relative risk: 3.63; 95% CI: 2.56 to 5.16). The results were robust regardless of the type of study or the hemostatic scale used. CONCLUSIONS The risk of death after severe DOAC-related bleeding remains significant despite a high rate of effective hemostasis with reversal agents. Failure to achieve effective hemostasis strongly correlated with a fatal outcome. Thromboembolism rates are particularly high with andexanet. Comparative clinical trials are needed. (J Am Coll Cardiol 2021;77:2987-3001) (c) 2021 by the American College of Cardiology Foundation.
引用
收藏
页码:2987 / 3001
页数:15
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