Extended prophylaxis for venous thromboembolism after hospitalization for medical illness: A trial sequential and cumulative meta-analysis
Extended prophylaxis for venous thromboembolism after hospitalization for medical illness: A trial sequential and cumulative meta-analysis
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DOI：
10.1371/journal.pmed.1002797
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发表时间：
2019-04-01
期刊：
影响因子：
15.8
通讯作者：
Mehra, Mandeep R.
中科院分区：
文献类型：
--
作者：
Bajaj, Navkaranbir S.;Vaduganathan, Muthiah;Mehra, Mandeep R.
长期血栓预防（EDT）用于预防内科患者静脉血栓栓塞（VTE）的有效性、安全性和临床重要性尚不清楚。我们比较了EDT在因内科疾病住院患者中的疗效和安全性。方法和结果电子数据库PubMed/MEDLINE、EMBASE、科克伦中心和ClinicalTrials.gov从开始到2019年3月21日进行了检索。我们纳入了报告使用EDT预防VTE的随机临床试验（RCT）。我们进行了试验序贯和累积荟萃分析，以评估EDT对症状性VTE或VTE相关死亡、国际血栓与止血学会（ISTH）严重或致死性出血和全因死亡率的主要疗效终点的影响。计算了预防1起症状性或致死性VTE事件所需治疗的汇总数量（NNT）和导致1起重大或致死性出血事件所需伤害的数量（NNH）。在5项随机对照试验中，40，247例患者（平均年龄：67-77岁，女性比例：48%-54%，最常见的入院原因：心力衰竭），EDT的持续时间范围为24-47天。与标准治疗相比，EDT降低了症状性VTE或VTE相关死亡（0.8% vs 1.2%;风险比[RR]：0.61，95%置信区间[CI]：0.44-0.83; p = 0.002）。在荟萃分析和试验序贯分析中，EDT增加了ISTH严重或致死性出血的风险（0.6% vs 0.3%; RR：2.04，95% CI：1.42-2.91; p < 0.001）。预防一例症状性VTE或VTE相关死亡的合并NNT为250例（95% CI：167-500），而导致一例重大或致死性出血事件的NNH为333例（95% CI：200- 1，000）。该研究的局限性包括变异的入组标准，个体化治疗，EDT的持续时间，和VTE检测协议在整个纳入的trials.Conclusions在这一系统性审查和荟萃分析5随机试验，我们观察到，使用出院后EDT策略为4至6周的时间减少症状性或致命性VTE事件的风险增加的代价，主要或致命性出血。仍需要进一步的研究来确定离散的医学疾病队列的风险和益处，评估成本效益，并制定有针对性地实施这种出院后EDT策略的途径。
Background The efficacy, safety, and clinical importance of extended-duration thromboprophylaxis (EDT) for prevention of venous thromboembolism (VTE) in medical patients remain unclear. We compared the efficacy and safety of EDT in patients hospitalized for medical illness.Methods and findings Electronic databases of PubMed/MEDLINE, EMBASE, Cochrane Central, and ClinicalTrials.gov were searched from inception to March 21, 2019. We included randomized clinical trials (RCTs) reporting use of EDT for prevention of VTE. We performed trial sequential and cumulative meta-analyses to evaluate EDT effects on the primary efficacy endpoint of symptomatic VTE or VTE-related death, International Society on Thrombosis and Haemostasis (ISTH) major or fatal bleeding, and all-cause mortality. The pooled number needed to treat (NNT) to prevent one symptomatic or fatal VTE event and the number needed to harm (NNH) to cause one major or fatal bleeding event were calculated. Across 5 RCTs with 40,247 patients (mean age: 67-77 years, proportion of women: 48%-54%, most common reason for admission: heart failure), the duration of EDT ranged from 24-47 days. EDT reduced symptomatic VTE or VTE-related death compared with standard of care (0.8% versus 1.2%; risk ratio [RR]: 0.61, 95% confidence interval [CI]: 0.44-0.83; p = 0.002). EDT increased risk of ISTH major or fatal bleeding (0.6% versus 0.3%; RR: 2.04, 95% CI: 1.42-2.91; p < 0.001) in both meta-analyses and trial sequential analyses. Pooled NNT to prevent one symptomatic VTE or VTE-related death was 250 (95% CI: 167-500), whereas NNH to cause one major or fatal bleeding event was 333 (95% CI: 200-1,000). Limitations of the study include variation in enrollment criteria, individual therapies, duration of EDT, and VTE detection protocols across included trials.Conclusions In this systematic review and meta-analysis of 5 randomized trials, we observed that use of a post-hospital discharge EDT strategy for a 4-to-6-week period reduced symptomatic or fatal VTE events at the expense of increased risk of major or fatal bleeding. Further investigations are still required to define the risks and benefits in discrete medically ill cohorts, evaluate cost-effectiveness, and develop pathways for targeted implementation of this postdischarge EDT strategy.