Antihypertensive effects and tolerability of candesartan cilexetil alone and in combination with amlodipine

Objective: This study aimed to compare the antihypertensive effect and tolerability of candesartan cilexetil, an angiotensin II type 1 (AT1) receptor blocker with a dose-dependent and long-lasting antihypertensive effect, with that of amlodipine, a widely used long-acting dihydropyridine calcium antagonist, and with that of a combination of candesartan cilexetil and amlodipine. Design: Multicentre, randomised, double-blind, placebo-controlled parallel-group study. Setting: 42 general practice centres in France, Hungary, Poland, South Africa and the United Kingdom. Patients: 341 men and women, aged 21 to 81 years, with primary hypertension and a sitting diastolic blood pressure (DBP) of 95 to 114mm Hg. Interventions: After a 4-week placebo run-in period, patients were randomised to once-daily treatment with candesartan cilexetil 8mg (n = 85), amlodipine 5mg (n = 84), candesartan cilexetil 8mg plus amlodipine 5mg (n = 89), or placebo (n = 83) for 8 weeks. Main Outcome Measures: Differences between treatments in change in blood pressure from randomisation to the end of the study were evaluated using analysis of covariance. Results: All active treatment regimens resulted in marked reductions in sitting and standing blood pressures compared with placebo (p < 0.001). Co-administration of candesartan cilexetil and amlodipine resulted in statistically significant and clinically important greater blood pressure reductions than either drug alone, with differences in adjusted mean systolic blood pressure (SBP)/DBP reductions of 5.6/2.0mm Hg (sitting) and 6.7/3.4mm Hg (standing) vs amlodipine; and of 5.8/0.8mm Hg (sitting) and 6.8/3.9mm Hg (standing) vs candesartan cilexetil (p < 0.05 for combination therapy vs both monotherapies, except for sitting DBP; not significant). All treatments were well tolerated. Conclusions: This study not only confirms the efficacy and tolerability of candesartan cilexetil and amlodipine in patients with primary hypertension, but also shows that their combination results in a clinically important enhancement of antihypertensive effect while maintaining tolerability.