Combination therapy with candesartan cilexetil 32 mg and hydrochlorothiazide 25 mg provides the full additive antihypertensive effect of the components: A randomized, double-blind, parallel-group study in primary care

Abstract

Background and objective: Fixed-combination tablets of candesartan (orally administered as the pro-drug candesartan cilexetil and hereafter referred to as candesartan) and hydrochlorothiazide (HCTZ) 8/12.5 mg and 16/12.5 mg are effective and well tolerated. However, some patients require higher doses to attain target blood pressure, and combination tablets containing candesartan and HCTZ at the upper end of their respective dose ranges are now being developed. This study aimed to assess the antihypertensive effect and tolerability of the combination of candesartan 32 mg and HCTZ 25 mg versus candesartan 32 mg monotherapy, HCTZ 25 mg monotherapy, and placebo.

Methods: This was a randomized, double-blind, parallel-group study, with 8 weeks of follow-up, carried out in primary-care outpatients. 1524 men or women (age 20-80 years) with mild to moderate primary hypertension and sitting diastolic blood pressure (DBP) 90-114 mmHg after 4 weeks' single-blind placebo treatment were included in the study. Candesartan/HCTZ 32/25 mg combination therapy, candesartan 32 mg monotherapy, HCTZ 25 mg monotherapy, and placebo, allocated in a 5 : 5 : 5 : 1 ratio, were administered once daily. The main outcome measure was adjusted (analysis of covariance) mean reductions in systolic blood pressure (SBP) and DBP.

Results: Mean reductions in SBP and DBP were significantly greater with candesartan/HCTZ 32/25 mg (21/14 mmHg) than with candesartan 32 mg (13/9 mmHg), HCTZ 25 mg (12/8 mmHg) or placebo (4/3 mmHg) [p < 0.001 for all comparisons]. The proportion of patients with controlled blood pressure (SBP <140 mmHg and DBP <90 mmHg) at the end of the study was also significantly greater in the candesartan/HCTZ 32/25 mg group (63%) than in the other treatment groups (p < 0.001 for all comparisons). All study treatments were generally well tolerated.

Conclusion: The antihypertensive effect of candesartan/HCTZ 32/25 mg represents fully additive contributions from each of its components, and is generally well tolerated in patients with mild to moderate primary hypertension. This combination adds to the treatment options for improving blood pressure control in patients with hypertension.