Abstract 3398: Comparison of Once Versus Twice a Day Valsartan Dosing in Heart Failure -Results of the DESTINY Trial

Abstract

Background. Valsartan causes a sustained 24-hour reduction in blood pressure (BP) in hypertensive patients, when given once a day (q.d.). Because many CHF patients have low baseline BP and concomitant chronic kidney disease, valsartan was prescribed twice a day (b.i.d.) in Val-HeFT (Valsartan in Heart Failure Trial) to avoid any possible adverse effects like symptomatic hypotension and worsening renal dysfunction with the q.d. dosing. Methods and Results. DESTINY-HF ( D iovan E valuation of S afety T w I ce vs o N ce dail Y study in H eart F ailure) was a 10-week double blind randomized trial designed to test the safety of q.d. (n=55) vs b.i.d. (n=60) dosing of valsartan in patients with NYHA class II–III heart failure receiving diuretics (87%), ACE-I (98%), beta-blockers (92%), aldosterone antagonists (25%) and digoxin (32%) over a 12-week period. Valsartan was started in the dose of 40 mg b.i.d. vs 80 mg q.d. and titrated to a maximum of 320 mg per day by doubling the dose every 2 weeks. Clinical and biochemical measurements were made at 2, 4, 6, and 10 weeks. The baseline characteristics of the two groups were similar. The average dose of valsartan at the end of study was 245 mg vs 256 mg in the bid vs qd dose groups (p=NS). The % of patients who tolerated the up-titration regimen at week 2, 4 and 6 and at the end of study were not significantly different between the dose groups (b.i.d. vs q.d., 75 vs 75, 74 vs 85, 77 vs 78, and 67 vs 68; p=NS). There was no difference in the reduction of systolic or diastolic BP, or in the incidence of hypotension, renal impairment, orthostatic dizziness or syncope between the groups at any time point. Changes in serum K + , creatinine, cystatin-C, and estimated GFR were also not different between the groups at any time point. Brain natriuretic peptide decreased, and by the same amount in both groups at all time points. Conclusions. These data demonstrate that the use of valsartan in q.d. dosing has the same safety profile as b.i.d. dosing in patients with moderate to severe heart failure.