Valsartan for the treatment of heart failure.
Heart failure (HF) still has a discouraging prognosis. Therapeutic strategies aim to reduce mortality as well as slow the progression of the disease, improve symptoms and reduce the frequency of hospital admission. Activation of the renin-angiotensin-aldosterone system (RAAS) is a hallmark of several cardiocirculatory diseases, including HF. Drugs for evidence-based therapy of HF are angiotensin-converting enzyme inhibitors (ACEIs), beta-blockers and aldosterone antagonists. A promising alternative is a more complete action on the RAAS through selective blockade of the angiotensin type 1 (AT(1)) receptors, taking into account not only physiopathological issues but also pharmacological, experimental and clinical data. The effect of valsartan, an orally-active, selective antagonist of AT(1) receptors, on the outcome in patients with chronic and symptomatic HF was evaluated in a large-scale, international, placebo-controlled clinical study, the Valsartan in Heart Failure Trial (Val-HeFT). In this study, overall mortality was similar in the valsartan and placebo groups (19.7 and 19.4%, respectively). However, valsartan, in addition to recommended therapy of HF including an ACEI, significantly reduced the combined end point of mortality and morbidity, with a significant reduction in the risk of hospitalisation, paralleled by improvements in New York Heart Association (NYHA) functional class, signs and symptoms and quality of life. Valsartan also improved left ventricular anatomy and function and significantly reduced neurohormonal activation. These results were confirmed and extended by the CHARM trial, where the benefits of candesartan were proved not only in all 7599 patients with HF, but also in the 2548 given an ACEI, the 2028 not given an ACEI and in the 3023 patients with an ejection fraction of > 40%. In conclusion, the first choice for HF remains an ACEI with a beta-blocker, but two new options are emerging. In patients intolerant to ACEI, the combination of valsartan or candesartan with a beta-blocker is proposed, whereas an ACEI with either valsartan or candesartan can be considered in patients intolerant to or with contraindications to beta-blockers.
Latini
Roberto
R
Department of Cardiovascular Research, Istituto di Ricerche Farmacologiche, Mario Negri, via Eritrea 62, 20157 Milan, Italy. latini@marionegri.it
Masson
Serge
S
Staszewsky
Lidia
L
Maggioni
Aldo P
AP
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D001562:Benzimidazoles / Q000493:pharmacokinetics; D001713:Biphenyl Compounds; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D019808:Losartan / Q000493:pharmacokinetics; D013777:Tetrazoles / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000068756:Valsartan
D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine; D019808:Losartan; C081643:candesartan