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

Objective: This study aimed to compare the antihypertensive effect and tole rability of candesartan cilexetil, an angiotensin II type 1 (AT(1)) recepto r blocker with a dose-dependent and long-lasting antihypertensive effect, w ith that of amlodipine, a widely used long-acting dihydropyridine calcium a ntagonist, and with that of a combination of candesartan cilexetil and amlo dipine. Design: Multicentre, randomised, double-blind, placebo-controlled parallel- group study. Setting: 42 general practice centres in France, Hungary, Poland, South Afri ca 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 randomis ed to once-daily treatment with candesartan cilexetil 8mg (n = 85), amlodip ine 5mg (n = 84), candesartan cilexetil 8mg plus amlodipine 5mg (n = 89), o r placebo (n = 83) for 8 weeks. Main Outcome Measures: Differences between treatments in change in blood pr essure from randomisation to the end of the study were evaluated using anal ysis of covariance. Results: All active treatment regimens resulted in marked reductions in sit ting and standing blood pressures compared with placebo (p < 0.001). Go-adm inistration of candesartan cilexetil and amlodipine resulted in statistical ly significant and clinically important greater blood pressure reductions t han either drug alone, with differences in adjusted mean systolic blood pre ssure (SBP)/DBP reductions of 5.6/2.0mm Hg (sitting) and 6.7/3.4mm Hg (stan ding) vs amlodipine; and of 5.8/0.8mm Hg (sitting) and 6.8/3.9mm Hg (standi ng) vs candesartan cilexetil (p < 0.05 for combination therapy vs both mono therapies, except for sitting DBP; not significant). All treatments were we ll 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 en hancement of antihypertensive effect while maintaining tolerability.