title: Time of administration important? Morning versus evening dosing of valsartan.
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.
  
  
  CONCLUSIONS
  Once-daily dosing of valsartan 320 mg results in equally effective 24-h BP efficacy, regardless of dosing time.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier: NCT00241124.
authors.affiliation: aNovartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA bNovartis Pharma AG, Basel, Switzerland cDepartment of Medicine, University of Padova, Padova, Italy.
authors.forename: Dion H
authors.initials: DH
authors.lastname: Zappe
authors.forename: Nora
authors.initials: N
authors.lastname: Crikelair
authors.forename: Albert
authors.initials: A
authors.lastname: Kandra
authors.forename: Paolo
authors.initials: P
authors.lastname: Palatini
mesh_terms: D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory; D002318:Cardiovascular Diseases / Q000188:drug therapy; D004311:Double-Blind Method; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage; D006973:Hypertension / Q000188:drug therapy*; D017706:Lisinopril / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D016896:Treatment Outcome; D000068756:Valsartan / Q000008:administration & dosage*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D006852:Hydrochlorothiazide; D000068756:Valsartan; D017706:Lisinopril