Time of administration important? Morning versus evening dosing of valsartan

Objective: Studies suggest that bedtime dosing of an angiotensin-converting enzyme (ACE)-inhibitor or angiotensin receptor blocker shows a more sustained and consistent 24-h antihypertensive profile, including greater night-time blood pressure (BP) reduction. We compared the antihypertensive effects of morning (a.m.) and evening (p.m.) dosing of valsartan on 24-h BP. Methods: This 26-week, multicentre, randomized, double-blind study evaluated the efficacy and safety of valsartan 320 mg, dosed a. m. or p. m., versus lisinopril 40mg (a.m.), a long-acting ACE-inhibitor, in patients with grade 1-2 hypertension and at least one additional cardiovascular risk factor. Patients (n = 1093; BP = 156 +/- 11/91 +/- 8 mmHg; 62 years, 56% male, 99% white) received (1 : 1 : 1) valsartan 160mg a. m. or p. m. or lisinopril 20mg a. m. for 4 weeks, then force-titrated to double the initial dose for 8 weeks. At Week 12, hydrochlorothiazide (HCTZ) 12.5mg was added for 14 weeks if office BP was more than 140/90mmHg and/or ambulatory BP more than 130/80 mmHg. Results: Mean 24-h ambulatory SBP change from baseline to Weeks 12 and 26 was comparable between valsartan a. m. (-10.6 and -13.3mmHg) and p. m. (-9.8 and -12.3 mmHg) and lisinopril (-10.7 and -13.7 mmHg). There was no benefit of valsartan p. m. versus a. m. on night-time BP, early morning BP and morning BP surge. Evening dosing also did not improve BP lowering in patients requiring add-on HCTZ or in nondippers at baseline. All treatments were well tolerated. Conclusion: Once-daily dosing of valsartan 320mg results in equally effective 24-h BP efficacy, regardless of dosing time.