Extended prophylaxis for venous thromboembolism after hospitalization for medical illness: A trial sequential and cumulative meta-analysis

• Published in: PLoS medicine 2019-04, Vol.16 (4), p.e1002797
• Main Authors: Bajaj, Navkaranbir S, Vaduganathan, Muthiah, Qamar, Arman, Gupta, Kartik, Gupta, Ankur, Golwala, Harsh, Butler, Javed, Goldhaber, Samuel Z, Mehra, Mandeep R
• Format: Article
• Language: English
• Subjects: Aged; Analysis; Anticoagulants - administration & dosage; Anticoagulants - adverse effects; Authorship; Bias; Bleeding; Cardiology; Care and treatment; Chemoprevention - adverse effects; Chemoprevention - methods; Chemoprevention - statistics & numerical data; Clinical trials; Cohort Studies; Congestive heart failure; Cost benefit analysis; Death; Drug Administration Schedule; Effectiveness; Embolisms; Female; Heart; Heart failure; Hospital admission and discharge; Hospital patients; Hospitalization; Hospitalization - statistics & numerical data; Hospitals; Humans; Internal medicine; Male; Management; Medical research; Medical schools; Medical Subject Headings-MeSH; Medicine; Meta-analysis; Mortality; Patients; Prophylaxis; Randomization; Randomized Controlled Trials as Topic - statistics & numerical data; Research methodology; Retirement benefits; Rivaroxaban; Safety and security measures; Systematic review; Thromboembolism; Thrombosis; Venous Thromboembolism - epidemiology; Venous Thromboembolism - prevention & control; Venous thrombosis
• ISSN: 1549-1676; 1549-1277; 1549-1676
• DOI: 10.1371/journal.pmed.1002797

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. 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. 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. PROSPERO CRD42018109151.