Subgroup analyses in venous thromboembolism trials reporting pharmacological interventions: A systematic review

Introduction: Randomized controlled trials (RCTs) that conduct subgroup analyses have the potential to provide information on treatment decisions in specific groups of patients from heterogeneous populations. Although we understand several factors can modify the incidence of venous thromboembolism (VTE) and the benefit/risk ratio of anticoagulation treatments, further evidence is warranted to show the heterogeneity of treatment effects in different subgroups of patients.

Aims: The primary purpose was to evaluate the appropriateness and interpretation of subgroup analysis performed on VTE RCTs reporting pharmacological interventions.

Materials and methods: A systematic review of RCTs published between January 2017 and January 2022 was conducted. Claims of subgroup effects were evaluated with predefined criteria. High-quality claims of subgroup effect were further analyzed and discussed.

Results: Overall, 28 RCTs with a generally low bias risk were included. The purposes of the treatments included pharmacologic thromboprophylaxis (17), therapeutic dose anticoagulation (9), and catheter-directed pharmacologic thrombolysis (2). The evaluated subgroup analyses generally presented: a high number of subgroup analyses reported, a lack of prespecification, and a lack of usage of statistical tests for interaction. The authors reported 13 claims of subgroup effect; only two were considered potentially reliable to represent heterogeneity in the direction or magnitude of treatment effect.

Conclusions: Subgroup analyses of VTE RCTs reporting pharmacologic interventions are generally methodologically poor. Most claims of subgroup effect did not meet critical criteria and lacked credibility. Clinicians in this field may proceed with scepticism when assessing claims of subgroup effects due to methodological concerns and misleading interpretations.