Search

The use of angiotensin-receptor blockers has already been outlined in cardiology and diabetology. In extending clinical indications of this drug class their pleiotropic actions might play a role: they are improving endothelial function, and their antiatherogenic effect is not related to antihypertensive action. It may also be important that while some antihypertensive agents are impairing sexual function, angiotensin-receptor blocking agents seem to improve sexual activity in hypertensive men. As there is alternative route for angiotensin II synthesis, there are patients in whom blockade of angiotensin II actions do need more aggressive treatment for proper therapeutic results. The discovery of angiotensin-receptor blocking agents made possible to produce this blockade in the tissues as well, and suggested combined administration of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for better clinical results. In patients with congestive heart failure data from an earlier pilot study (RESOLVD) suggested that combined use of these two drug classes would lead for a more complete blockade of the renin-angiotensin system with better clinical results, especially in those patients in the higher dose ranges. Recent results showed that using this drug combination cardiovascular mortality and hospitalization because of worsening heart failure could significantly be decreased (CHARM-Added study). More important data are expected from the ongoing ONTARGET program (Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial).

The angiotensin (II) receptor (1) blockers are known first of all as antihypertensive drugs, however, due to the role of the tissue renin-angiotensin system (RAS) in different pathological conditions, their clinical importance became more pronounced and are at present more widely used. The article gives an overview of the recent knowledge in this field. Beside of summarizing physiological and the most important pathophysiological aspects of the RAS, as well as pharmacokinetic properties of the different angiotensin receptor blocker drugs used at present in Hungary, the potential differences in blocking of the converting enzyme and the angiotensin II receptors are also reviewed.

The PICXEL study is designed to evaluate the effects of long-term administration of very low-dose combination perindopril 2 mg/indapamide 0.625 mg (Per/Ind) vs enalapril in reducing left ventricular hypertrophy (LVH) in hypertensive patients. This multicentre, controlled, randomised, double-blind, parallel group study is carried-out to assess the variation of left ventricular mass index (LVMI) after treatment, using a centralised control of M-mode echocardiography determinations, and a dedicated software for semi-automatic measurement. Following a 4-week placebo run-in period, hypertensive outpatients aged >/=18 years, with LVH (LVMI >120 and 100 g/m(2) for men and women, respectively), are randomised to receive once daily, over 52 weeks, either Per/Ind or enalapril. According to blood pressure levels, the dose may be adjusted. In addition to clinical examinations, ECG, blood pressure, heart rate and laboratory assessments echocardiographic determinations are performed for selection, at baseline, after 24 weeks and at the end of the study. The main outcome criteria is the change from baseline in LVMI which is considered the primary efficacy criterion; changes in blood pressure and echo-Doppler parameters constitute secondary criteria. Two-sided Student's t-test for independent samples will be used to differentiate the effects of the treatment between groups with alpha = 5%, and the inter-group difference of LVMI variation will be analysed with a power of 90%. A sample size of 500 patients is required making it necessary to randomise at least 550 patients, based on a 10% proportion of potentially non-assessable patients. The results of this study, obtained after applying strict methodological procedures and requirements, are expected to provide valuable and reliable information on the effects of long-term administration of Per/Ind on LVH, and on its potential superiority over enalapril.