Rationale for the use of sartans in patients with arterial hypertension

Abstract

Angiotensin II (ATII) receptor antagonists, the drugs that affect the basic links of neuro-humoral regulation: the renin-angiotensin-aldosterone (RAAS) and sympathicoadrenal systems, have currently found wide use in clinical cardiology. By blocking the specific ATII receptors, the agents of this group contributes to systemic vasodilation, cell growth inhibition, including to the suppressed proliferation of endothelial and smooth muscle cells of the vascular wall, fibro-blasts, and to the inhibited cardiomyocytic hypertrophy. ATII receptor antagonists are referred to as first-line drugs used in the treatment of arterial hypertension (AH) in young patients in whom RAAS activity is generally increased, in that of diabetes mellitus since the drugs of this group are able to reduce the degree of microalbuminuria/proteinuria, and in the complex therapy for chronic heart failure (CHF). One of the representatives of this group is valsartan, a non-heterocyclic derivative, has a double elimination pathway (the liver and kidneys), a sustained 24-hour antihypertensive effect after single administration, which allows its once-daily dosing, by correcting systolic and diastolic blood pressure in more than 70% of patients. It should be emphasized that adjustment of the dose of valsartan is not required in moderately diminished hepatic or renal function. Valsartan failed to exert a negative effect on the level of glycemia and to cause changes in lipid profile and triglyceride levels. The long-term use of valsartan as mono-therapy for AH requires that the safety of treatment should not undergo additional laboratory monitoring. A multicenter, double-blind, placebo-controlled Val-HeFT trial covering 5010 pa-tients with CHF and a left ventricular ejection fraction (EF) of less than 40%, demonstrated that valsartan produced good clinical effects. Although overall mortality (one of the primary end points) was similar in the valsartan and placebo groups; another end point (reductions in the risk of mortality and morbidity) and the frequency of hospitalizations for increased symptoms of CHF was decreased in the valsartan group by 13.2 and 27.5%; respectively. In addition, valsar-tan was found to have a positive effect on a number of secondary end points: quality of life sig-nificantly improved, EF of the left ventricle rose, its dimensions decreased, and the degree of CHF symptoms was reduced, exercise tolerance increased, and the plasma levels of norepineph-rine, atrial natriuretic peptide, and aldosterone were decreased. The adverse reactions caused by ATII antagonists are seen rather rarely, which provides high patient compliance to some extent. The contraindications to the use of ATII antagonists are their hypersensitivity, arterial hypotension, hyperkalemia, dehydration, bilateral renal artery stenosis, pregnancy, childhood.