Kolkailah Ahmed A, Abdelghaffar Bahaa, Elshafeey Farida, Magdy Rana, Kamel Menna, Abuelnaga Yasmeen, Nabhan Ashraf F, Piazza Gregory
Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic Florida, Weston, FL, USA.
Cochrane Database Syst Rev. 2024 Dec 4;12(12):CD014541. doi: 10.1002/14651858.CD014541.pub2.
Venous thromboembolism (VTE) includes two interrelated conditions, deep vein thrombosis (DVT) and pulmonary embolism (PE). Risk factors include dehydration, prolonged immobilization, acute medical illness, trauma, clotting disorders, previous thrombosis, varicose veins with superficial vein thrombosis, exogenous hormones, malignancy, chemotherapy, infection, inflammation, pregnancy, obesity, smoking, and advancing age. It is estimated that hospitalized patients are 100 times more likely to develop VTE and, compared with surgical patients, medical patients often have more severe forms of VTE. VTE carries a significant risk of morbidity and mortality. Prophylactic strategies, including mechanical and pharmacological methods, are recommended for patients at risk of VTE. Pharmacological prophylaxis is considered the standard practice for acutely ill medical patients at risk of developing VTE in the absence of contraindications. For hospitalized patients, the risk of VTE extends beyond hospital stay and up to 90 days, with most events occurring within 45 days of discharge. Despite that, it remains unclear whether extended-duration anticoagulation for primary VTE prophylaxis would provide benefits without added risks or harm.
To assess the benefits and risks of standard- versus extended-duration anticoagulation for primary VTE prophylaxis in acutely ill medical patients.
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialized Register, CENTRAL, MEDLINE, Embase, CINAHL and Web of Science databases, as well as the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers up to 27 March 2023. We also searched reference lists of all included studies for additional references and searched the last five years of the American Society of Hematology conference proceedings.
We included randomized controlled trials (RCTs) comparing standard-duration versus extended-duration anticoagulation for primary VTE prophylaxis in acutely ill medical patients (adults being treated in a medical inpatient setting).
We used the standard methodological procedures set by Cochrane. At least two authors independently screened titles and abstracts for inclusion and performed data extraction. Two authors independently assessed the risk of bias (RoB) using the Cochrane RoB 2 tool. We analyzed outcomes data using the risk ratio (RR) with 95% confidence intervals (CIs). We used the GRADE approach to assess the certainty of evidence for each outcome. Our outcomes of interest were assessed in the short term (during the treatment period and within 45 days of hospitalization) and long term (assessed beyond 45 days of hospitalization). Primary outcomes were symptomatic VTE, major bleeding, and all-cause mortality. Secondary outcomes were total VTE, a composite of fatal and irreversible vascular events (including myocardial infarction, non-fatal PE, cardiopulmonary death, stroke), fatal bleeding, and VTE-related mortality.
A total of seven RCTs fulfilled our inclusion criteria, comprising 40,846 participants. All studies contributing data to our outcomes were at low risk of bias in all domains. Most studies reported the outcomes in the short term. Extended-duration anticoagulation, compared with standard-duration anticoagulation, for primary VTE prophylaxis in acutely ill medical patients reduced the risk of short-term symptomatic VTE (RR 0.60, 95% CI 0.46 to 0.78; standard-duration 12 per 1000, extended-duration 7 per 1000, 95% CI 6 to 10; number needed to treat for an additional beneficial outcome [NNTB] 204, 95% CI 136 to 409; 4 studies, 24,773 participants; high-certainty evidence). This benefit, however, was offset by an increased risk of short-term major bleeding (RR 2.05, 95% CI 1.51 to 2.79; standard-duration 3 per 1000, extended duration 6 per 1000, 95% CI 5 to 8; number needed to treat for an additional harmful outcome [NNTH] 314, 95% CI 538 to 222; 7 studies, 40,374 participants; high-certainty evidence). Extended-duration anticoagulation, compared with standard-duration, results in little to no difference in short-term all-cause mortality (RR 0.97, 95% CI 0.87 to 1.08; standard-duration 34 per 1000, extended-duration 33 per 1000, 95% CI 30 to 37; 5 studies, 38,080 participants; high-certainty evidence), reduced short-term total VTE (RR 0.75, 95% CI 0.67 to 0.85; standard-duration 37 per 1000, extended duration 28 per 1000, 95% CI 25 to 32; NNTB 107, 95% CI 76 to 178; 5 studies, 33,819 participants; high-certainty evidence), and short-term composite of fatal and irreversible vascular events (RR 0.71, 95% CI 0.56 to 0.91; standard-duration 41 per 1000, extended-duration 29 per 1000, 95% CI 23 to 37; NNTB 85, 95% CI 50 to 288; 1 study, 7513 participants; high-certainty evidence). Extended-duration anticoagulation may result in little to no difference in short-term fatal bleeding (RR 2.28, 95% CI 0.84 to 6.22; standard-duration 0 per 1000, extended-duration 0 per 1000, 95% CI 0 to 1; 7 studies, 40,374 participants; low-certainty evidence), and likely results in little to no difference in short-term VTE-related mortality (RR 0.78, 95% CI 0.58 to 1.05; standard-duration 5 per 1000, extended-duration 4 per 1000 95% CI 3 to 6; 6 studies, 36,170 participants; moderate-certainty evidence).
AUTHORS' CONCLUSIONS: In the short term, extended- versus standard-duration anticoagulation for primary VTE prophylaxis in acutely ill medical patients reduced the risk of symptomatic VTE at the expense of an increased risk of major bleeding. Extended-duration anticoagulation resulted in little to no difference in all-cause mortality. Extended-duration anticoagulation reduced the risk of total VTE and the composite of fatal and irreversible vascular events, but may show little to no difference in fatal bleeding and VTE-related mortality. Further data, with longer follow-up, are needed to determine the optimal agent and duration for primary VTE prophylaxis in acutely ill medical patients.
静脉血栓栓塞症（VTE）包括两种相互关联的病症，即深静脉血栓形成（DVT）和肺栓塞（PE）。风险因素包括脱水、长期制动、急性内科疾病、创伤、凝血障碍、既往血栓形成、伴有浅静脉血栓形成的静脉曲张、外源性激素、恶性肿瘤、化疗、感染、炎症、妊娠、肥胖、吸烟和年龄增长。据估计，住院患者发生VTE的可能性比普通人群高100倍，并且与外科患者相比，内科患者的VTE往往更为严重。VTE具有显著的发病和死亡风险。对于有VTE风险的患者，推荐采取包括机械和药物方法在内的预防策略。在没有禁忌证的情况下，药物预防被认为是有发生VTE风险的急性内科患者的标准做法。对于住院患者，VTE风险不仅限于住院期间，还可延续至出院后90天，大多数事件发生在出院后45天内。尽管如此，对于原发性VTE预防进行延长疗程的抗凝治疗是否能在不增加风险或危害的情况下带来益处仍不明确。
评估在急性内科患者中，标准疗程与延长疗程抗凝用于原发性VTE预防的益处和风险。
Cochrane血管信息专家检索了Cochrane血管专科注册库、CENTRAL、MEDLINE、Embase、CINAHL和Web of Science数据库，以及世界卫生组织国际临床试验注册平台和ClinicalTrials.gov试验注册库，检索截至2023年3月27日的数据。我们还检索了所有纳入研究的参考文献列表以获取更多参考文献，并检索了美国血液学会会议论文集的最近五年内容。
我们纳入了比较标准疗程与延长疗程抗凝用于急性内科患者（在内科住院环境中接受治疗的成年人）原发性VTE预防的随机对照试验（RCT）。
我们采用Cochrane制定的标准方法程序。至少两名作者独立筛选标题和摘要以确定是否纳入，并进行数据提取。两名作者使用Cochrane偏倚风险2工具独立评估偏倚风险（RoB）。我们使用风险比（RR）及95%置信区间（CI）分析结局数据。我们采用GRADE方法评估每个结局的证据确定性。我们感兴趣的结局在短期（治疗期间及住院45天内）和长期（住院45天后评估）进行评估。主要结局为有症状的VTE、大出血和全因死亡率。次要结局为总的VTE、致命和不可逆血管事件的复合结局（包括心肌梗死、非致命性PE、心肺死亡、中风）、致命性出血和VTE相关死亡率。
共有7项RCT符合我们的纳入标准，包括40,846名参与者。所有为我们的结局提供数据的研究在所有领域的偏倚风险均较低。大多数研究报告了短期结局。在急性内科患者中，与标准疗程抗凝相比，延长疗程抗凝用于原发性VTE预防可降低短期有症状VTE的风险（RR 0.60，95%CI 0.46至0.78；标准疗程每1000人中有12例，延长疗程每1000人中有7例，95%CI 6至10；获得额外有益结局所需治疗人数[NNTB] 204，95%CI 136至409；4项研究，24,773名参与者；高确定性证据）。然而，这一益处被短期大出血风险增加所抵消（RR 2.05，95%CI 1.51至2.79；标准疗程每1000人中有3例，延长疗程每1000人中有6例，95%CI 5至8；获得额外有害结局所需治疗人数[NNTH] 314，95%CI 538至222；7项研究，40,374名参与者；高确定性证据）。与标准疗程相比，延长疗程抗凝在短期全因死亡率方面几乎没有差异（RR 0.97，95%CI 0.87至1.08；标准疗程每1000人中有34例，延长疗程每1000人中有33例，95%CI 30至3
