Rationale for a single-pill combination of perindopril arginine and amlodipine besylate

A systematic review identified 86 outcome-based clinical trials involving perindopril, amlodipine, or other antihypertensive drugs. In fixed-effects meta-analyses of 11 clinical trials (90,208 subjects), amlodipine was associated with a significant 24% increase in heart failure, but a significant decrease in death, cardiovascular death, stroke, coronary heart disease, and first major cardiovascular adverse event. In five clinical trials (52,565 subjects), perindopril was associated with a significant reduction in all six cardiovascular endpoints. Network and Bayesian meta-analyses suggested that (with the exception of amlodipine and heart failure), each agent was at least as effective as an initial diuretic to prevent these events. Short-term trials have demonstrated that the combination of perindopril and amlodipine is safe and effective, with statistically greater lowering of blood pressure than either agent alone and a potential synergistic effect on pedal edema. The single-pill combination of perindopril and amlodipine may be a useful addition to the antihypertensive armamentarium.