Time of administration important? Morning versus evening dosing of valsartan

J Hypertens. 2015 Feb;33(2):385-92. doi: 10.1097/HJH.0000000000000397.

Abstract

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 40 mg (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 160 mg a.m. or p.m. or lisinopril 20 mg a.m. for 4 weeks, then force-titrated to double the initial dose for 8 weeks. At Week 12, hydrochlorothiazide (HCTZ) 12.5 mg was added for 14 weeks if office BP was more than 140/90 mmHg 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 -13.3 mmHg) 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 320 mg results in equally effective 24-h BP efficacy, regardless of dosing time.

Trial registration: ClinicalTrials.gov Identifier: NCT00241124.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Angiotensin II Type 1 Receptor Blockers / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Antihypertensive Agents / administration & dosage*
  • Blood Pressure / drug effects*
  • Blood Pressure Monitoring, Ambulatory
  • Cardiovascular Diseases / drug therapy
  • Double-Blind Method
  • Humans
  • Hydrochlorothiazide / administration & dosage
  • Hypertension / drug therapy*
  • Lisinopril / administration & dosage
  • Male
  • Middle Aged
  • Risk Factors
  • Treatment Outcome
  • Valsartan / administration & dosage*

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Hydrochlorothiazide
  • Valsartan
  • Lisinopril

Associated data

  • ClinicalTrials.gov/NCT00241124