Comparison of once-daily versus twice-daily dosing of valsartan in patients with chronic stable heart failure.
BACKGROUND
The safety of once-daily (qd) dosing of valsartan in heart failure (HF) patients is not known.


OBJECTIVE
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.


CONCLUSIONS
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.
Anand
Inder S
IS
Department of Cardiology, Veterans Administration Medical Center, Minneapolis, MN 55417, USA. anand001@umn.edu
Deswal
Anita
A
Kereiakes
Dean J
DJ
Purkayastha
Das
D
Zappe
Dion H
DH
D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D055316:Cystatin C / Q000097:blood; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D011188:Potassium / Q000097:blood; D012083:Renin / Q000097:blood; D013777:Tetrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014633:Valine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; D055316:Cystatin C; D013777:Tetrazoles; D020097:Natriuretic Peptide, Brain; D000068756:Valsartan; D003404:Creatinine; D012083:Renin; D014633:Valine; D011188:Potassium