Ambulatory blood pressure in hypertensive patients with left ventricular hypertrophy: efficacy of first-line combination perindopril/indapamide therapy.

BACKGROUND: Ambulatory blood pressure (BP) is more sensitive than office BP and is highly correlated with the left ventricular mass (LVM) of hypertensive patients with left ventricular hypertrophy (LVH). METHODS: In this prospectively designed ancillary study of the PICXEL trial, the effects of first-line combination perindopril/indapamide on ambulatory BP were compared with those of monotherapy with enalapril in 127 patients. Hypertensive patients with LVH received once daily either perindopril 2 mg/indapamide 0.625 mg (n = 65) or enalapril 10 mg (n = 62) for 52 weeks. Dose adjustments were allowed for uncontrolled BP. Twenty-four-hour ambulatory BP and echocardiographic parameters were measured at baseline, week 24, and week 52. RESULTS: At study end, both treatments significantly improved ambulatory BP compared with baseline (p < or = 0.01). Perindopril/indapamide treatment reduced 24-hour and daytime systolic BP (SBP) and pulse pressure (PP) significantly more than enalapril treatment (p < 0.01). No significant between-group differences were noted for diastolic BP (DBP) or for night-time measurements. Trough/peak ratios were higher with perindopril/indapamide than with enalapril (88.5 vs 65.8 for SBP and 86.7 vs 63.9 for DBP, respectively). The global smoothness index was higher with perindopril/indapamide than with enalapril (6.6 vs 5.2 for SBP and 5.6 vs 4.9 for DBP, respectively). With perindopril/indapamide treatment, LVM index was significantly reduced (-9.1 g/m2 from baseline; p vs baseline <0.001). More patients required dose increases with enalapril (87%) than with perindopril/indapamide (71%). No unusual safety elements were noted. CONCLUSIONS: First-line perindopril/indapamide combination decreased ambulatory SBP and PP, and LVM more effectively than enalapril.

Perindopril/indapamide combination more effective than enalapril in reducing blood pressure and left ventricular mass: the PICXEL study.

OBJECTIVE: Few data are available comparing the effects of monotherapy and combination therapy on target organ damage. The PICXEL study compared the efficacy of a strategy based on first-line combination with perindopril/indapamide versus monotherapy with enalapril in reducing left ventricular hypertrophy (LVH) in hypertensive patients. METHODS: In this 1-year multicentre randomized double-blind study, patients received an increasing dosage of perindopril/indapamide (n = 284) or enalapril (n = 272). Changes in blood pressure and echocardiographic measures of LVH were assessed from baseline to the end of treatment. Reading of the echocardiograms was central and blinded for therapy, patient and sequence. RESULTS: Systolic and diastolic blood pressure decreased significantly more in the perindopril/indapamide than in the enalapril group (P < 0.0001 and P = 0.003). The left ventricular mass index decreased by 13.6 +/- 23.9 g/m(2) (mean +/- SD) with perindopril/indapamide (P < 0.0001) and 3.9 +/- 23.9 g/m(2) with enalapril (P < 0.005); these decreases were significantly different (P < 0.0001). The left ventricular internal diameter, posterior and interventricular septal wall thickness decreased significantly with perindopril/indapamide (P < or = 0.0001); the interventricular septal wall thickness decreased significantly with enalapril (P < 0.001). Both treatments were well tolerated. CONCLUSION: A strategy based on first-line combination with perindopril/indapamide achieved better blood pressure decrease with a significantly greater degree of LVH reduction than a strategy based on monotherapy with enalapril in hypertensive patients with LVH.

[Cardiologic and diabetologic aspects of therapy with angiotensin receptor blocking agents]. / Az angiotenzin II-receptor-gátlás klinikai alkalmazásának kardiológiai és diabetológiai aspektusai.

Authors based on studies fullfiling the principles of evidence based medicine review the efficiency and benefits of angiotensin receptor blocking agents in congestive heart failure and hypertension. Special attention is focused on their application in diabetes mellitus. The data support efficacy, good tolerability, beneficial side effect profile as well as cardio- and renoprotective properties of these drugs. Their safety in diabetic as well as and in non-diabetic persons can be underlined.

[Theoretical background of angiotensin II receptor blockade and its features in clinical pharmacology]. / Az angiotenzin II-receptor-gátlás elméleti háttere és klinikofarmakológiai sajátosságai.

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.

[New possibilities in clinical use of angiotensin II receptor inhibitors]. / Az angiotenzin II-receptor-gátlók klinikai alkalmazásának új lehetóségei.

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).