Direct Oral Anticoagulants Versus Phenprocoumon: Mortality, Thromboembolism and Major Hemorrhage. A Systematic Review and Meta-Analysis of Routine Data Studies.

IF 8.7 2区医学 Q1 MEDICINE, GENERAL & INTERNAL

Deutsches Arzteblatt international Pub Date : 2026-07-10 DOI:10.3238/arztebl.m2026.0064

Christiane Engelbertz, Holger Reinecke, Jeanette Köppe

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引用次数: 0

Abstract

Background: In the randomized controlled trials (RCTs) of the non-vitamin K dependent oral anticoagulants (NOACs) that led to their approval, the vitamin K antagonist (VKA) warfarin was used as a comparator drug. The efficacy and safety of NOACs compared to phenprocoumon, the VKA predominantly used in Germany, are unknown, as it has not been studied in RCTs.

Methods: For this systematic review and meta-analysis (registration: CRD42024619047), we systematically searched 3 databases for studies based on routine data that yielded matched or adjusted results for overall mortality, thromboembolism, and major hemorrhage in anticoagulant-naïve patients who were treated with either phenprocoumon or a NOAC.

Results: Seven studies based on German routine data were identified, covering a total of 1 842 015 anticoagulant-naïve patients. In a pooled analysis of all NOACs (apixaban, dabigatran, edoxaban, and rivaroxaban), these were associated with a notably higher risk of mortality (hazard ratio [HR] 1.14, 95% confidence interval [1.00; 1.30]), a higher risk of thromboembolic events (HR 1.08, [1.01; 1.15]), and a lower risk of major hemorrhages (HR 0.80, [0.72; 0.90]) than phenprocoumon. Among individual NOACs, rivaroxaban was associated with a notably higher risk of mortality than phenprocoumon; the other NOACs also displayed a higher risk of mortality than phenprocoumon, but the differences were not statistically significant.

Conclusion: In this meta-analysis of NOACs versus phenprocoumon, the former were found in a pooled analysis to be associated with a higher overall risk of mortality and a higher risk of thromboembolic events on the one hand, but a lower risk of major hemorrhages on the other hand. Warfarin was the comparator drug in all of the clinical trials that led to the approval of NOAC. The findings of this meta-analysis cast doubt on the benefit of the preferential use of NOACs in countries where phenprocoumon is the standard VKA.

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直接口服抗凝剂与Phenprocoumon：死亡率、血栓栓塞和大出血。常规数据研究的系统回顾和荟萃分析。

背景：在获得批准的非维生素K依赖性口服抗凝剂（NOACs）的随机对照试验（RCTs）中，维生素K拮抗剂（VKA）华法林被用作比较药物。与phenprocoumon（德国主要使用的VKA）相比，noac的有效性和安全性尚不清楚，因为它尚未在随机对照试验中进行研究。方法：在这项系统评价和荟萃分析（注册号：CRD42024619047）中，我们系统地检索了3个数据库，以常规数据为基础，对使用phenprocoumon或NOAC治疗的anticoagulant-naïve患者的总体死亡率、血栓栓塞和大出血得出匹配或调整的结果。结果：根据德国常规数据纳入7项研究，共纳入1 842 015例anticoagulant-naïve患者。在对所有noac（阿哌沙班、达比加群、依多沙班和利伐沙班）的汇总分析中，与phenprocoumon相比，noac的死亡风险明显较高（风险比[HR] 1.14, 95%可信区间[1.00;1.30]），血栓栓塞事件风险较高（风险比1.08,[1.01;1.15]），大出血风险较低（风险比0.80,[0.72;0.90]）。在单个noac中，利伐沙班与死亡率风险显著高于苯丙单抗；其他noac的死亡风险也高于phenprocoumon，但差异无统计学意义。结论：在这项NOACs与phenprocoumon的荟萃分析中，合并分析发现前者一方面与较高的总体死亡风险和较高的血栓栓塞事件风险相关，但另一方面与较低的大出血风险相关。华法林是所有临床试验的比较药物这些临床试验导致了NOAC的批准。本荟萃分析的结果对在phenprocoumon为标准VKA的国家优先使用noac的益处提出了质疑。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Deutsches Arzteblatt international 医学-医学：内科

CiteScore

4.10

自引率

5.20%

发文量

306

审稿时长

4-8 weeks

期刊介绍： Deutsches Ärzteblatt International is a bilingual (German and English) weekly online journal that focuses on clinical medicine and public health. It serves as the official publication for both the German Medical Association and the National Association of Statutory Health Insurance Physicians. The journal is dedicated to publishing independent, peer-reviewed articles that cover a wide range of clinical medicine disciplines. It also features editorials and a dedicated section for scientific discussion, known as correspondence. The journal aims to provide valuable medical information to its international readership and offers insights into the German medical landscape. Since its launch in January 2008, Deutsches Ärzteblatt International has been recognized and included in several prestigious databases, which helps to ensure its content is accessible and credible to the global medical community. These databases include: Carelit CINAHL (Cumulative Index to Nursing and Allied Health Literature) Compendex DOAJ (Directory of Open Access Journals) EMBASE (Excerpta Medica database) EMNursing GEOBASE (Geoscience & Environmental Data) HINARI (Health InterNetwork Access to Research Initiative) Index Copernicus Medline (MEDLARS Online) Medpilot PsycINFO (Psychological Information Database) Science Citation Index Expanded Scopus By being indexed in these databases, Deutsches Ärzteblatt International's articles are made available to researchers, clinicians, and healthcare professionals worldwide, contributing to the global exchange of medical knowledge and research.