The consistency of the treatment effect of an ACE-inhibitor based treatment regimen in patients with vascular disease or high risk of vascular disease: a combined analysis of individual data of ADVANCE, EUROPA, and PROGRESS trials

Abstract

Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce cardiovascular risk in different groups of patients. Whether these effects can be generalized to the broad group of patients with vascular disease is unknown. Therefore, we undertook a combined analysis using individual data from ADVANCE, EUROPA, and PROGRESS to determine the consistency of the treatment effect of perindopril-based regimen in patients with vascular disease or at high risk of vascular disease. We studied all-cause mortality and major cardiovascular outcomes during a follow-up of about 4 years in the 29 463 patients randomly assigned a perindopril-based treatment regimen or placebo. The perindopril-based regimens were associated with a significant reduction in all-cause mortality [hazard ratio (HR) 0.89; 95% confidence interval (CI) 0.82-0.96; P = 0.006], cardiovascular mortality (HR 0.85; 95% CI 0.76-0.95; P = 0.004), non-fatal myocardial infarction (HR 0.80; 95% CI 0.71-0.90; P < 0.001), stroke (HR 0.82; 95% CI 0.74-0.92; P = 0.002), and heart failure (HR 0.84; 95% CI 0.72-0.96; P = 0.015). Results were consistent in subgroups with different clinical characteristics, concomitant medication use, and across all strata of baseline blood pressure. This study provides strong evidence for a consistent cardiovascular protection with an ACE-inhibitor treatment regimen (perindopril-indapamide) by improving survival and reducing the risk of major cardiovascular events across a broad spectrum of patients with vascular disease.