Time of administration important? Morning versus evening dosing of valsartan

Zappe, Dion H.a; Crikelair, Noraa; Kandra, Albertb; Palatini, Paoloc

doi: 10.1097/HJH.0000000000000397
ORIGINAL PAPERS: Therapeutic aspects

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.

aNovartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA

bNovartis Pharma AG, Basel, Switzerland

cDepartment of Medicine, University of Padova, Padova, Italy

Correspondence to Dion H. Zappe, Clinical Development, Novartis Pharmaceuticals, One Health Plaza, East Hanover, NJ 07936, USA. Tel: +1 8627782935; fax: +1 9737812657; e-mail: dion.zappe@novartis.com

Abbreviations: ABPM, ambulatory blood pressure monitoring; ACE, angiotensin-converting enzyme; ANCOVA, analysis of covariance; ARB, angiotensin receptor blocker; CABS, coronary artery bypass surgery; CI, confidence interval; HCTZ, hydrochlorothiazide; maDBP, mean ambulatory DBP; maSBP, mean ambulatory SBP; MI, myocardial infarction; msDBP, mean sitting DBP; msSBP, mean sitting SBP; PCTA, percutaneous transluminal coronary angioplasty; RAAS, renin–angiotensin–aldosterone system; SAE, serious adverse event; SD, standard deviation; T2DM, type 2 diabetes mellitus

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Received March 28, 2014

Received in revised form August 26, 2014

Accepted August 26, 2014

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