24-Hour ambulatory blood pressure control with triple-therapy amlodipine, valsartan and hydrochlorothiazide in patients with moderate to severe hypertension

To determine the effectiveness and safety of once-daily combination therapy with amlodipine, valsartan and hydrochlorothiazide for reducing ambulatory blood pressure (ABP) in patients with moderate to severe hypertension, a multicenter, double-blind study was performed (N=2271) that included ABP monitoring in a 283-patient subset. After a single-blind, placebo run-in period, patients were randomized to receive amlodipine/valsartan/hydrochlorothiazide (10/320/25 mg), valsartan/hydrochlorothiazide (320/25 mg), amlodipine/valsartan (10/320 mg) or amlodipine/hydrochlorothiazide (10/25 mg) each morning for 8 weeks. Efficacy assessments included change from baseline in 24-h, daytime and night time mean ambulatory systolic BP (SBP) and diastolic BP (DBP). Statistically significant and clinically relevant reductions from baseline in all these parameters occurred in all treatment groups (P<0.0001, all comparisons versus baseline). At week 8, least squares mean reductions from baseline in 24-h, daytime and night time mean ambulatory SBP/DBP were 30.3/19.7, 31.2/20.5 and 28.0/17.8 mm Hg, respectively, with amlodipine/valsartan/hydrochlorothiazide; corresponding reductions with dual therapies ranged from 18.8–24.1/11.7–15.5, 19.0–25.1/12.0–16.0 and 18.3–22.6/11.1–14.3 mm Hg (P⩽0.01, all comparisons of triple versus dual therapy). Treatment with amlodipine/valsartan/hydrochlorothiazide maintained full 24-h effectiveness, including during the morning hours; all hourly mean ambulatory SBP and mean ambulatory DBP measurements were ⩽130/85 mm Hg at end point. Amlodipine/valsartan/hydrochlorothiazide combination therapy was well tolerated. Once-daily treatment with amlodipine/valsartan/hydrochlorothiazide (10/320/25 mg) reduces ABP to a significantly greater extent than component-based dual therapy and maintains its effectiveness over the entire 24-h dosing period

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\u200amg, dosed a.m. or p.m., versus lisinopril 40\u200amg (a.m.), a long-acting ACE-inhibitor, in patients with grade 1-2 hypertension and at least one additional cardiovascular risk factor. Patients (n\u200a=\u200a1093; BP\u200a=\u200a156\u200a\ub1\u200a11/91\u200a\ub1\u200a8\u200ammHg; 62 years, 56% male, 99% white) received (1\u200a:\u200a1\u200a:\u200a1) valsartan 160\u200amg a.m. or p.m. or lisinopril 20\u200amg a.m. for 4 weeks, then force-titrated to double the initial dose for 8 weeks. At Week 12, hydrochlorothiazide (HCTZ) 12.5\u200amg was added for 14 weeks if office BP was more than 140/90\u200ammHg and/or ambulatory BP more than 130/80\u200ammHg. RESULTS:: Mean 24-h ambulatory SBP change from baseline to Weeks 12 and 26 was comparable between valsartan a.m. (-10.6 and -13.3\u200ammHg) and p.m. (-9.8 and -12.3\u200ammHg) and lisinopril (-10.7 and -13.7\u200ammHg). 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 320\u200amg results in equally effective 24-h BP efficacy, regardless of dosing time