Perindopril: do randomised, controlled trials support an ACE inhibitor class effect? A meta-analysis of clinical trials

BACKGROUND: Due to the lack of face-to-face trials between ACE inhibitors, clinicians and third-party funders may assume they provide similar outcomes. As a result, ACE inhibitors may be prescribed interchangeably and deemed to provide the same outcomes for all patients when used chronically, that is for more than six months. OBJECTIVE: This meta-analysis aims to dispute the assumption of a class effect when prescribing ACE inhibitors (ACEIs), since the evidence from all the clinical trials is not uniform and therefore a direct comparison is impossible. METHODS: Published randomised, controlled trials were selected using an applicable literature search for all ACEIs, irrespective of drug combination, for any cardiovascular outcome (both composite and individual outcomes were included). The average length of ACEI exposure per trial had to be longer than six months). This meta-analysis was performed using odds ratios as the parameter of efficacy in a fixed-effects model. RESULTS/CONCLUSION: Perindopril resulted in significantly fewer patients reaching the primary endpoint versus all other ACEIs combined. The results were consistent for myocardial infarction, stroke and mortality (5 vs 11%, p = 0.0001). Perindopril alone or as part of combination therapy in clinical trials seemed to deliver clear and consistent outcome differences compared to other ACEI trials. In the presence of positive outcomes from robust randomised, controlled trials for perindopril, one cannot assume a class effect for all ACEIs.