Telmisartan/Amlodipine: Single-pill combination in hypertension.. - (Page 653)

Telmisartan: A Review 653 Table I. List of study acronyms and their definitions Study ADVANCE AMADEO CHARM DETAIL HOPE INNOVATION LIFE ONTARGET PRoFESS TRANSCEND TRENDY VaL-HeFT VALIANT VALUE VIVALDI Definition Action in diabetes and vascular disease: preterax and diamicron modified release controlled evaluation A comparison of telmisartan versus losartan in hypertensive type 2 diabetic patients with overt nephropathy Candesartan in heart failure: assessment of reduction in mortality and morbidity Diabetics exposed to telmisartan and enalapril Heart outcomes prevention evaluation Incipient to overt: angiotensin II blocker, telmisartan, investigation on type 2 diabetic nephropathy Losartan intervention for endpoint reduction Ongoing telmisartan alone and in combination with ramipril global endpoint trial Prevention regimen for effectively avoiding second strokes Telmisartan randomized assessment study in ACE intolerant subjects with cardiovascular disease Telmisartan versus ramipril on renal endothelium function in type 2 diabetes Valsartan in congestive heart failure trial Valsartan in acute myocardial infarction Valsartan antihypertensive long-term use evaluation [Trial to] investigate the efficacy of telmisartan versus valsartan in hypertensive type 2 diabetic patients with overt nephropathy treatment of essential hypertension in adults.[10] In addition, it is indicated for CVD prevention (i.e. the reduction of cardiovascular morbidity in patients with manifest atherothrombotic CVD [history of coronary heart disease, stroke or peripheral arterial disease] and those with type 2 diabetes and documented target organ damage).[10] This article focuses on the indication for telmisartan in CVD prevention, and reviews pharmacological, clinical and tolerability data relevant to the use of the drug in this setting. Trial acronyms used in this article are defined in table I. 2. Pharmacodynamic Properties ANG II is thought to mediate its pathophysiological effects (e.g. vasoconstriction, oxidative stress and inflammation) through AT1 receptors, which are primarily found in blood vessels, the liver, kidneys, heart and brain. ANG II type 2 (AT2) receptors are located in many of the same organs as AT1 receptors, but are generally thought to have physiologically opposing actions.[11] In vitro, telmisartan showed a high affinity for the AT1 receptor (inhibition constant [Ki] 3.7 nmol/L[12]), but little or no affinity for the AT2 receptor (Ki >10000 nmol/L).[8] The drug ª 2011 Adis Data Information BV. All rights reserved. had the strongest binding affinity to the AT1 receptor among five commercially available ARBs evaluated in an in vitro study,[13] with the rank order of affinity being telmisartan > olmesartan medoxomil > candesartan cilexetil ‡ valsartan ‡ losartan. The corresponding dissociation rate constants were 0.0032, 0.0042, 0.0052, 0.0099 and 0.010 per minute, with dissociation half-lives of 213, 166, 133, 70 and 67 minutes, respectively.[13] Slow dissociation of telmisartan from the AT1 receptor may account for the insurmountable antagonism displayed by the drug.[14] Telmisartan is a partial agonist of the peroxisome proliferator-activated receptor-g (PPAR)-g.[15] Briefly, PPARg is a ligand-activated transcription factor that regulates cell growth, inflammation, lipid metabolism and insulin sensitivity; PPARg agonists have been shown (among other actions) to decrease the risk of atherosclerosis, improve insulin sensitivity and reduce triglyceride levels.[16] At clinically relevant concentrations, telmisartan caused substantial (27-fold) activation of the PPARg in vitro; this corrresponded to 25–30% of the maximum level of activation achieved by the full PPARg agonists pioglitazone and rosiglitazone in this assay.[17] In comparison, irbesartan and losartan showed only slight (2- to 3-fold) activation; olmesartan medoxomil, 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..