Angiotensin Receptor Blockers: Pharmacology, Efficacy, and Safety

Abstract

Key Points and Practical Recommendations• The angiotensin receptor blockers are highly effective antihypertensive agents that are also particularly well tolerated.• There are no major differences in efficacy or other clinical characteristics among older drugs in this class, although some of the newer agents may more effectively reduce blood pressure than older agents.• Major randomized clinical trials have demonstrated that angiotensin receptor blockers provide significant outcomes benefits in conditions such as diabetic nephropathy, chronic heart failure or heart failure following myocardial infarction, hypertension with left ventricular hypertrophy and in patients whose histories of previous events or complicated diabetes puts them at high cardiovascular risk.• In treating hypertension, angiotensin receptor blockers can be used as first-line therapy or added at later stages of treatment titration.• These drugs are very effective in combination with thiazide diuretics or calcium channel blockers and there are several single-pill, fixed-dose combinations of angiotensin receptor blockers with hydrochlorothiazide, amlodipine, or aliskiren. These combinations can be given as initial therapy (where appropriate) or later in the course of treatment. Three-drug combinations (angiotensin receptor blocker plus amlodipine plus hydrochlorothiazide and angiotensin receptor blocker plus aliskiren plus hydrochlorothiazide) are also available. J Clin Hypertens (Greenwich). 2011;13:677-686. Ó2011 Wiley Periodicals, Inc.The renin-angiotensin-aldosterone system (RAAS) plays an important role in protecting vertebrates against cardiovascular collapse due to hypotension and volume loss in the event of traumatic injury that involves blood loss. In certain humans, however, inappropriate or exaggerated activity of the RAAS contributes to the development of hypertension and the initiation of a molecular cascade in tissues with consequent injury to critical organs such as the brain, kidneys, heart, and blood vessels. 1-3 As understanding of the pathologic role of the RAAS in hypertensive vascular disease has unfolded during the past century, so has the interest in developing drugs that could interdict specific components of the RAAS. The first of the RAAS-blocking drugs to become commercially available were the aldosterone antagonists in the 1970s, followed by the angiotensin-converting enzyme (ACE) inhibitors in the 1980s and the angiotensin II receptor blockers (ARBs) in the 1990s. Unlike ACE inhibitors that inhibit the conversion of angiotensin I to II, ARBs bind to the angiotensin II AT 1 receptor, thereby inhibiting the cellular actions of angiotension II mediated by the receptor in which the tissue is located. During the past 20 years, studies in the laboratory and clinic have documented that ARBs, either alone or in combination with drugs of other classes, reduce blood pressure (BP) in hypertensive animals and humans; reduce rates of myocardial infarction (MI), stroke, and progression of renal impairment; and positively impact oth...

Current Research of the Renin-Angiotensin System Effect on Stem Cell Therapy

“…On the other hand, RAS inhibition via ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) has been widely examined in cardiovascular disease beyond their efects in lowering the blood pressure [67]. Despite the daily increasing use of regenerative medicine in treating diferent disorders, the functionality of stem cell transplantation is not suicient in animal models and clinical trials [68].…”

Does Outcome Reporting Bias “Cause” Cancer? Risks Associated with Hidden Data on Angiotensin Receptor Blockers

“…8 There is also evidence from animal models that unopposed AT2R stimulation (when AT1Rs are blocked by ARBs) can lead to tumour progression. 7 Although this has yet to be shown in humans, tumour progression caused by AT2R stimulation is the proposed mechanism for the increased incidence of cancer within ARB treatment groups in clinical trials. [7][8][9] ARBs are commonly prescribed inhibitors of the renin-angiotensin-aldosterone system and are the alternative to angiotensin-converting enzyme (ACE) inhibitors in cases of allergy or intolerance.…”

“…7 Although this has yet to be shown in humans, tumour progression caused by AT2R stimulation is the proposed mechanism for the increased incidence of cancer within ARB treatment groups in clinical trials. [7][8][9] ARBs are commonly prescribed inhibitors of the renin-angiotensin-aldosterone system and are the alternative to angiotensin-converting enzyme (ACE) inhibitors in cases of allergy or intolerance. 11 Indications for ARBs approved by Health Canada are hypertension, heart failure, diabetic nephropathy, and secondary prevention of cardiovascular events.…”

“…The AT1Rs are located in the kidney, heart, brain, vascular smooth muscle cells, placenta, platelets, and fat cells, whereas the AT2Rs are important in fetal development, although their function is not well understood. 6,7 In vitro studies have shown that agonism at both of the angiotensin receptor subtypes (AT1R and AT2R) is involved in the regulation of cellular proliferation, angiogenesis, and tumour progression. 6,[8][9][10] ARBs exert their clinical effect through ATR1 antagonism, and it is postulated that they may have anti-angiogenic properties, thereby suppressing tumour growth.…”

The effect of angiotensin II receptor blockers on hyperuricemia

“…While utilized for similar indications, the available ARBs differ widely in their chemical structures, which correlate to various differences in their pharmacodynamic and pharmacokinetic effects. Overall, ARBs are well tolerated; however, the most common adverse effects include hypotension, hyperkalemia and increased serum creatinine levels [Taylor et al 2011].…”