Do drugs interact together in cardiovascular prevention? A meta-analysis of powerful or factorial randomized controlled trials

Therapie. 2022 Nov-Dec;77(6):663-672. doi: 10.1016/j.therap.2022.04.004. Epub 2022 May 1.

Abstract

Aim of the study: To explore whether preventive cardiovascular drugs (antihypertensive, antiplatelet, lipid lowering and hypoglycemic agents) interact together in cardiovascular prevention.

Methods: We searched PubMed®, Web of science™, Embase and Cochrane library for powerful randomized placebo-controlled trials (>1000 patients). We explored whether drug effect on major vascular events changed according to cross-exposure to other drug classes or to cardiovascular risk factors (hypertension or type 2 diabetes), through a meta-analysis of relative odds ratio computed by trial subgroups. A significant interaction was suggested from confidence intervals of the ratio of odds ratios, when they excluded neutral value of 1.

Results: In total, 14 trials with 178,398 patients were included. No significant interaction was observed between co-prescribed drugs or between these medications and type 2 diabetes/hypertension status.

Conclusions: Our meta-analysis is the first one to evaluate drug-drug and drug-hypertension/type 2 diabetes status interactions in terms of cardiovascular risks: we did not observe any significant interaction. This indirectly reinforces the rationale of using several contrasted mechanisms to address cardiovascular prevention; and allows the combination effect prediction by a simple multiplication of their odds ratios. The limited availability of data reported or obtained from authors is a strong argument in favor of data sharing.

Keywords: Drug; Interaction; Major vascular event; Meta-analysis; Pharmacodynamics; Primary/secondary prevention.

Publication types

  • Meta-Analysis

MeSH terms

  • Antihypertensive Agents / therapeutic use
  • Cardiovascular Diseases* / epidemiology
  • Cardiovascular Diseases* / prevention & control
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / epidemiology
  • Diabetes Mellitus, Type 2* / prevention & control
  • Humans
  • Hypertension* / drug therapy
  • Hypertension* / epidemiology
  • Randomized Controlled Trials as Topic

Substances

  • Antihypertensive Agents