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

• Outcomes from clinical trials using perindopril or amlodipine were meta–analyzed.
• Amlodipine increased heart failure by 24%, but decreased five other outcomes.
• Perindopril significantly decreased the incidence of all six cardiovascular outcomes.
• Network and Bayesian meta–analyses of larger datasets corroborated these results.
• The combination of these two agents may be a useful antihypertensive therapy.

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.