Assessment of the optimal daily dose of valsartan in patients with hypertension, heart failure, or both.
BACKGROUND
Recent data suggest that use of relatively high doses of angiotensin II-receptor blockers (ARBs) in hypertensive patients at high cardiovascular risk may reduce the incidence of clinical complications to a greater extent than would be predicted based on blood-pressure (BP) lowering alone. There is also evidence that a sustained reduction in BP, however small, may be important in reducing the risk of cardiovascular disease. Therefore, it is necessary to determine the ARB dosages that optimize the efficacy/tolerability ratio.


OBJECTIVE
This article reviews experimental and clinical studies of the ARB valsartan to define the daily dose that provides the best ratio between efficacy and tolerability in patients with hypertension, heart failure, or both.


METHODS
Relevant studies were identified through searches of EMBASE and Science Citation Index for articles published before December 15, 2003. No language restrictions were applied. Search terms were angiotensin II-receptor blockers, cardiovascular disease, hypertension, heart failure, type 2 diabetes mellitus, and angiotensin-converting enzyme inhibitors.


RESULTS
In several randomized, double-blind, dose-finding studies, the antihypertensive effect of valsartan increased in a predictable fashion over a wide dose range (20-320 mg). The antihypertensive efficacy of the 80-mg dose was enhanced by doubling it to 160 mg, and the tolerability profile remained comparable to that of placebo over a broad dose range. Valsartan has been investigated in patients with heart failure at dosages ranging from 40 to 160 mg BID. Because of the need for careful individualization of therapy in these patients, rigid dose standardization may not be appropriate.


CONCLUSIONS
Based on the efficacy/tolerability profile of valsartan at various doses, it appears that 160 mg may be the optimal dose for initial therapy in patients with essential hypertension and in most patients with heart failure.
Verdecchia
Paolo
P
Department of Cardiovascular Disease, Hospital R. Silvestrini, University of Perugia, S. Andrea delle Fratte, 06122 Perugia, Italy. verdec@tin.it
Angeli
Fabio
F
D000804:Angiotensin II / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D013777:Tetrazoles / Q000008:administration & dosage* / Q000627:therapeutic use; D014633:Valine / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000627:therapeutic use; D000068756:Valsartan
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D013777:Tetrazoles; D000804:Angiotensin II; D000068756:Valsartan; D014633:Valine