Systematic Review: Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers for Treating Essential Hypertension

Matchar, David B.; McCrory, Douglas C; Orlando, Lori A.; Patel, Manesh R.; Patel, Uptal D.; Patwardhan, Meenal; Powers, Benjamin; Samsa, Gregory P.; Gray, Rebecca N

doi:10.7326/0003-4819-148-1-200801010-00189

Cited by 324 publications

(238 citation statements)

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“…The report did note that BP outcomes in trials of longer duration, eg, up to 5 years, were confounded by the coadministration of other antihypertensive drugs in some patients. 35 Since the publication of these reports on the comparative BP-lowering effects of specific ARBs, a new ARB, azilsartan medoxomil (AZL), has been approved by the FDA based on the prespecified primary efficacy criterion of lowering mean 24-hour ambulatory systolic BP rather than the more traditional analysis of seated office trough diastolic BP reduction. 36 There are relatively few studies that have directly compared specific ARBs in the same patient population.…”

Section: Efficacy Of Arbs In Hypertensionmentioning

confidence: 99%

Angiotensin Receptor Blockers: Pharmacology, Efficacy, and Safety

Taylor

Siragy

Nesbitt

2011

The Journal of Clinical Hypertension

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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...

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Section: Efficacy Of Arbs In Hypertensionmentioning

confidence: 99%

Angiotensin Receptor Blockers: Pharmacology, Efficacy, and Safety

Taylor

Siragy

Nesbitt

2011

The Journal of Clinical Hypertension

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“…2 Angiotensin-converting enzyme inhibitors (ACEis) can provide all the same clinical benefits if not more than those provided by ARBs. 3,4 However, ARBs are generally better tolerated as they are associated with a significantly lower risk of cough and angioedema than ACE inhibitors. [4][5][6][7] Renin inhibitors represent a more recently developed class of molecules also designed to inhibit activity of the renin-angiotensin system (RAS) and lower blood pressure.…”

Section: Introductionmentioning

confidence: 99%

Next generation multifunctional angiotensin receptor blockers

Kurtz

Klein

2009

Hypertens Res

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Angiotensin receptor blockers (ARBs) are well-tolerated drugs that are known to be useful for inhibiting activity of the reninangiotensin (RAS) system, treating hypertension and reducing the risk for cardiovascular disease. However, inhibition of the RAS does not control all pathophysiological mechanisms of hypertension or cardiovascular risk and many patients continue to suffer from cardiovascular events and metabolic disturbances despite being treated with an ARB, an angiotensin-converting enzyme inhibitor or both, in addition to other standard therapies for cardiovascular disease. Recently, it has become apparent that bifunctional molecules can be designed that do more than just block AT 1 receptors and that can target additional mechanisms of hypertension, cardiovascular disease and diabetes besides just increased activity of the renin-angiotensin system. Specifically, next generation ARBs are becoming available that are intended to not only antagonize AT 1 receptors, but also block endothelin receptors, function as nitric oxide donors, inhibit neprilysin activity and increase natriuretic peptide levels, or stimulate the peroxisome proliferator-activated receptor c (PPARc). In this review, we: (1) discuss the potential importance of multifunctional ARBs that can reduce cardiovascular and metabolic risk through multiple mechanisms that go beyond just inhibition of the renin-angiotensin system and (2) describe specific examples of next generation ARBs in development that are intended to do more than simply block AT 1 receptors.

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“…This may be the reason why the editorialist commenting on ONTARGET stated, "ARBs have more side effects than ACE inhibitors," 11 despite the common knowledge that they do not. 12 …”

Section: The Misleading Trialmentioning

confidence: 99%