Efficacy and Safety of Incremental Dosing of a New Single-Pill Formulation of Perindopril and Amlodipine in the Management of Hypertension

BackgroundAngiotensin-converting enzyme inhibitors and calcium channel blockers in combination are widely recommended in hypertension guidelines. The advantages of single-pill combinations (SPCs) are increasingly recognized, so a dosage-adapted combination of perindopril and amlodipine was developed for the initial management of hypertension.ObjectiveThis randomized trial evaluated the blood pressure (BP)-lowering efficacy of four incremental doses of perindopril/amlodipine SPC in adults with mild-to-severe hypertension.MethodsEligible patients (N=1617) were randomized to SPC perindopril 3.5mg/amlodipine 2.5mg (i.e., 3.5/2.5mg) daily, uptitrating as required on a monthly basis up to 14/10mg until BP<140/90mmHg (<130/80mmHg in patients with diabetes). The primary endpoint (proportion with controlled BP at each uptitrated dose) was evaluated at 6months, and safety was evaluated at 9months; 24-h ambulatory BP measurement and BP variability were also investigated. Control-arm participants (n=1653) were randomized to irbesartan 150mg daily, uptitrating over 3months to irbesartan/hydrochlorothiazide 300/25mg.ResultsSignificant increases in BP control were observed with each dosage increment of perindopril/amlodipine, which was well tolerated, rising from 21% (3.5/2.5mg) to 30% (7/5mg), 37% (14/5mg), and 42% (14/10mg) after 1, 2, 3, and 6months, respectively. Reductions in mean systolic and diastolic BP occurred with each incremental dose of perindopril/amlodipine. After 6months, mean BP had fallen by 24.8/10.8mmHg. Irbesartan-based therapy reduced clinic and 24-h BP similarly to perindopril/amlodipine, but perindopril/amlodipine reduced BP variability more in comparison.ConclusionsIncremental uptitration with dosage-adapted perindopril/amlodipine SPC is a safe and effective strategy for managing hypertension.Trial registrationEudraCT (No. 2006-005799-42).