Adding hydrochlorothiazide to olmesartan dose dependently improves 24-h blood pressure and response rates in mild-to-moderate hypertension

OBJECTIVE: To test whether adding hydrochlorothiazide (HCTZ) (12.5 or 25 mg) to olmesartan 20 mg improves 24-h blood pressure in patients whose conventional diastolic blood pressure is inadequately controlled by olmesartan monotherapy. PATIENTS: Male and female patients > or = 18 years with mean sitting diastolic blood pressure (DBP) of 100-115 mmHg, mean sitting systolic blood pressure (SBP) greater than 150 mmHg, mean 24-h DBP of at least 84 mmHg, and at least 30% of DBP daytime readings > 90 mmHg. INTERVENTIONS: Four weeks of single-blind treatment with olmesartan 20 mg once daily, followed in non-responders by 8 weeks of randomized double-blind treatment with placebo or HCTZ (12.5 or 25 mg) once-daily, added to olmesartan. RESULTS: HCTZ 25 mg added to olmesartan 20 mg decreased mean daytime DBP significantly more (P = 0.0012) than placebo added to olmesartan 20 mg. Compared to olmesartan monotherapy, mean 24-h DBP and SBP were significantly reduced by combination therapy with olmesartan/HCTZ 20/12.5 mg (-1.9 mmHg, P = 0.0167 and -3.9 mmHg, P = 0.0018, respectively) and 20/25 mg (-3.7 and -7.4 mmHg respectively, P < 0.0001 for both). Mean 24-h DBP and SBP and mean night-time SBP reductions were significantly greater for HCTZ 25 mg than for HCTZ 12.5 mg. Response rates (mean daytime DBP assessed by ambulatory blood pressure measurement < or = 85 mmHg) approximately doubled following the addition of HCTZ (12.5 mg = 57.6% and 25 mg = 69.5%). CONCLUSION: Combination of olmesartan 20 mg with HCTZ provides significantly better 24-h blood pressure reduction than olmesartan monotherapy in patients with mild-to-moderate hypertension. Moreover, increasing the dose of HCTZ from 12.5 to 25 mg is a reasonable step to reach better daytime and night-time blood pressure control.