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

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00294086.

Keywords: angiotensin receptor blocker; heart failure; valsartan.

Figures

Figure 1

Percentage of patients tolerating valsartan once-daily (qd) or twice-daily (bid) dosing regimen using observed cases. Using data from observed cases, the percentage of patients able to tolerate the dosing regimen at the end of the study was 78% for bid dosing and 72% for qd dosing (P = 0.56). Inability to tolerate the dosing regimen was defined as any of the following: serum potassium ≥6.0 mEq/L, elevations in serum creatinine ≥2.5 mg/dL and increased by >50% from baseline, reduction in standing SBP (<90 mmHg), symptoms related to hypotension (eg, syncope, faintness, or orthostatic dizziness), worsening of NYHA functional class (eg, fatigue or breathlessness) in patients with stable CHF (NYHA class II–III).