Venous thromboembolism (VTE) prevention strategies do not have an effect on mortality, according to results from a large set of prospective, randomized trials published in The Lancet Haematology. Moreover, VTE is unjustifiably perceived as a cause of mortality and should instead be perceived as a marker of mortality.
To assess the causal effect of VTE reduction on mortality, the authors conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) that evaluated VTE prevention.
They searched major literature databases for studies published between January 1, 1993, and March 19, 2018. Studies of patients who were at elevated risk of VTE and were randomly assigned to receive anticoagulant or antiplatelet therapy vs placebo or no treatment were included in the meta-analysis. The primary endpoint was overall mortality, and secondary endpoints were pulmonary embolism (PE), fatal PE, and major bleeding.
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In total, 4229 studies were screened and 86 RCTs were included in the analysis. The investigators focused on studies that reported statistically significant effects of prevention on VTE endpoints.
There were 52 positive studies, which included data from more than 70,000 patients. Among these studies, patients in the control groups had a significantly increased risk for VTE compared with the treatment groups (median risk ratio [RR], 2.74; 95% credible interval [CrI], 2.32-3.31; P <.0001).
There was no causal effect of VTE prevention on mortality (RR, 1.01; 95% CrI, 0.97-1.06; P =.58). Among patients in control groups, the mortality rate was 9.8% (3391/34,537), and among patients in treatment groups, the mortality rate was also 9.8% (3498/35,795).
However, patients in control groups experienced higher rates of PE (RR, 2.22; 95% CrI, 1.78-2.89; P <.0001) and fatal PE (RR, 1.58; 95% CrI: 1.14-2.19; P =.01) compared with the treatment groups. Patients in the control groups had fewer major bleeding events than patients in the treatment groups (RR, 0.60; 95% CrI: 0.47-0.75; P <.0001).
In addition, the 34 negative studies included in the meta-analysis yielded similar results to those of the positive studies for all endpoints with the exception of fatal pulmonary embolism, which had weaker effect (RR, 1.42; 95% CrI, 1.05-1.91; P =.02).
“The perception that venous thromboembolism is a common cause of mortality should be revised considering the null effect of venous thromboembolism prevention on mortality,” wrote the authors. “Our findings call into question the use of composite endpoints in venous thromboembolism-prevention trials and provide rationale for de-escalation trials.”
The authors highlighted important limitations of their study. They tested an endpoint
without taking the treatment strategy used into consideration; thus, the studies included in the meta-analysis had assessed a variety of drugs and doses. Many of the studies excluded patients who had a very high risk of VTE. Additionally, many patients had competing risks that could have masked VTE prevention benefits, and the meta-analysis may have been underpowered to detect small survival benefits.
Disclosures: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Reference
Klemen ND, Feingold PL, Hashimoto B, et al. Mortality risk associated with venous thromboembolism: a systematic review and Bayesian meta-analysis. Lancet Haematol. 2020;7(8):e583-e593. doi:10.1016/S2352-3026(20)30211-8
