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

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.