Telmisartan/Amlodipine: Single-pill combination in hypertension.. - (Page 654)

654 Frampton candesartan cilexetil and eprosartan showed 1-fold activation.[17] Telmisartan, like the full PPARg agonist, pioglitazone, significantly improved glucose tolerance and insulin sensitivity in diet-induced obese mice (p < 0.05 vs vehicle control).[18] However, bodyweight decreased in telmisartan-treated animals, whereas it increased in pioglitazone- or vehicle-treated animals (both p < 0.05 vs telmisartantreated animals).[18] This suggests telmisartan may be an example of a selective PPARg modulator, i.e. it retains the beneficial metabolic properties of (full) PPARg agonists, but avoids the adverse events associated with these agents (e.g. sodium retention, peripheral oedema and weight gain).[16] The ability of telmisartan to activate PPARg appears to be independent of its ability to block AT1 receptors.[18] Telmisartan increased adiponectin levels (a marker of PPARg activation) in many clinical studies; the effect of the drug was greater than that of valsartan, candesartan cilexetil and irbesartan.[15] The remainder of this section focuses on the anti-inflammatory, endothelial, metabolic, cardiovascular and renal effects of telmisartan that have been observed in clinical studies (table II) and which may underlie the demonstrable benefits of the drug in terms of preventing cardiovascular events (section 4). 2.1 Anti-Inflammatory Effects In clinical studies, telmisartan decreased plasma levels of C-reactive protein (a marker of inflammation)[21-23] [table II]. In comparison, valsartan showed no such effect,[23] whereas olmesartan medoxomil had a more pronounced effect than telmisartan in Japanese patients[21] In animal models, telmisartan reduced oxidative stress,[58-61] including that induced by ANG II.[60,61] It also suppressed the expression of cell adhesion molecules and inflammatory cytokines,[62-64] reduced the infiltration of monocyte/macrophages into the vascular wall[64] and decreased the formation Table II. Overview of the pharmacodynamic effects of telmisartan observed in clinical studiesa Anti-inflammatory effects Reduced CRP levels in pts with T2DM with[21] or without[22] hypertension, and in hypertensive pts with metabolic syndrome[23] Endothelial effects Improved endothelial function in pts with hypertension,[24] and in pts with T2DM with[25,26] or without[19] hypertension Reduced arterial stiffness in hypertensive pts with[27] or without[28] T2DM Metabolic effects Improved[24,29-35] or had a neutral effect[36,37] on insulin sensitivity in hypertensive pts with[29,36] or without[24,30,31] T2DM, hypertensive pts with metabolic syndrome,[33-35,37,38]b and pts with T2DM and metabolic syndrome[32] Improved lipid profilec in hypertensive pts with[26,39-41] or without[42] T2DM Cardiovascular effects Reduced BP in a broad spectrum of hypertensive pts, including the elderly and those with T2DM, metabolic syndrome and/or renal impairment[8] Reduced LVH in hypertensive pts[20,43-51] Prevented recurrence of AF in hypertensive pts with a recent history of AF[52] Renal effects Reduced transition from incipient to overt nephropathy and induced remission of albuminuria in pts with T2DM with or without hypertension[53] Slowed decline of GFR in pts with T2DM, hypertension and early nephropathy[54] Reduced proteinuria in pts with T2DM, hypertension and overt nephropathy[55,56] Reduced microalbuminuria in hypertensive pts with[23] or without[57] metabolic syndrome a b c Some studies available only as abstracts/posters.[19,20] Pts had elevated BP or hypertension.[33] Reduced TC,[26,39,40] LDL-C[26,39,40] and/or triglyceride[26,40-42] levels. AF = atrial fibrillation; BP = blood pressure; CRP = C-reactive protein; GFR = glomerular filtration rate; LDL-C = low-density lipoproteincholesterol; LVH = left ventricular hypertrophy; pts = patients; T2DM = type 2 diabetes mellitus; TC = total cholesterol. ª 2011 Adis Data Information BV. All rights reserved. Drugs 2011; 71 (6)

Table of Contents for the Digital Edition of Telmisartan/Amlodipine: Single-pill combination in hypertension..

Telmisartan/Amlodipine: Single-pill combination in hypertension..
Contents
Abstract
Introduction
Pharmacodynamic Properties
Anti-Inflammatory Effects
Endothelial Effects
Metabolic Effects
Cardiovascular Effects
Renal Effects
Cerebrovascular Effects
Pharmacokinetic Properties
Drug Interactions
Therapeutic Efficacy
ONTARGET
TRANSCEND
PRoFESS
Pooled Analyses of the TRANSCEND and PRoFESS studies
Tolerability
Comparisons with Placebo

Telmisartan/Amlodipine: Single-pill combination in hypertension..