Comparison of once-daily versus twice-daily dosing of valsartan in patients with chronic stable heart failure

Original Research

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Authors: Inder S Anand, Anita Deswal, Dean J Kereiakes, et al

Published Date June 2010 Volume 2010:6 Pages 449 - 455

DOI: http://dx.doi.org/10.2147/VHRM.S11090

Inder S Anand¹, Anita Deswal², Dean J Kereiakes³, Das Purkayastha⁴, Dion H Zappe⁴

¹Veterans Administration Medical Center, Minneapolis, MN, USA; ²Michael E DeBakey VA Medical Center, Houston, TX, USA; ³The Christ Hospital Heart and Vascular Center, Cincinnati, OH, USA; ⁴Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; Clinical trial registration information: www.clinicaltrials.gov/ct2/show/NC T00294086 Unique identification number: NC T00294086

Background: The safety of once-daily (qd) dosing of valsartan in heart failure (HF) patients is not known. Hypothesis: This 10-week, double-blind trial examined the relative safety and efficacy of valsartan administered qd versus twice-daily (bid).

Methods: HF patients (NYHA class II–III) receiving diuretics (87%), angiotensin-converting enzyme inhibitors (98%), beta-blockers (92%), aldosterone antagonists (25%), or digoxin (32%) were randomized to valsartan 40 mg bid (n = 60) or 80 mg qd (n = 55) and titrated to a maximum dose of 320 mg/day; doubling the dose every 2 weeks. Clinical and biochemical parameters were measured at Weeks 2, 4, 6, and 10.

Results: The average dose of valsartan at the end of study was 245 mg in the bid group vs 256 mg in the qd group (P = NS). Similar proportions of patients tolerated qd vs bid dosing (bid 67% vs qd 68%). Outcome measures including reduction in blood pressure, incidence of hypotension, renal impairment, orthostatic dizziness or fatigue, changes in serum K⁺, creatinine, cystatin-C, and estimated glomerular filtration rate were similar between the 2 groups at all time-points. Brain natriuretic peptide levels decreased and plasma renin activity increased from baseline by the same amount in both groups at all time-points.

Conclusion: Valsartan administered qd has a similar safety and tolerability profile with comparable 24-hour RAAS blockade, as assessed by increases in PRA, as bid dosing in patients with moderate to severe (NYHA class II–III) heart failure.

Keywords: heart failure, angiotensin receptor blocker, valsartan