Mortality risk associated with venous thromboembolism: a systematic review and Bayesian meta-analysis

Area of Science:

• Cardiovascular Medicine
• Clinical Trials
• Epidemiology

Background:

• Venous thromboembolism (VTE) is linked to increased mortality, but its direct contribution to death is not well-established.
• Evaluating the impact of VTE reduction on mortality is crucial for clinical practice and research.

Purpose of the Study:

• To determine the causal effect of VTE prevention on overall mortality using data from randomized controlled trials (RCTs).
• To analyze the impact of VTE prevention on secondary endpoints including pulmonary embolism, fatal pulmonary embolism, and major bleeding.

Main Methods:

• Systematic review and meta-analysis of RCTs comparing VTE prevention therapies (anticoagulants/antiplatelets) with placebo or no treatment.
• Inclusion criteria: patients at elevated VTE risk, availability of mortality data. Exclusion criteria: active control agents, unavailable mortality data.
• Bayesian modeling for heterogeneity, with overall mortality as the primary endpoint and PE, fatal PE, and major bleeding as secondary endpoints.

Main Results:

• VTE prevention showed a null effect on overall mortality (RR 1.01, 95% CrI 0.97-1.06).
• Control groups had higher risks of pulmonary embolism (RR 2.22) and fatal pulmonary embolism (RR 1.58), but lower risks of major bleeding (RR 0.60).
• Analysis including negative studies confirmed the null effect on mortality and weakened evidence for fatal PE reduction.

Conclusions:

• The perception of VTE as a frequent cause of death needs revision due to the null effect of prevention on mortality.
• Findings question the utility of composite endpoints in VTE prevention trials and support de-escalation strategies.