Renin Angiotensin Aldosterone System Blockade: Little to No Rationale for ACE Inhibitor and ARB Combinations

Holdiness, Amber; Monahan, Ken; Minor, Deborah S.; Shazo, Richard de

doi:10.1016/j.amjmed.2010.07.021

Cited by 15 publications

(6 citation statements)

References 35 publications

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“…It is noteworthy that, in this age group, there are no ARBs, lipid-lowering drugs or antiglaucoma medications that are used. The use of ARBs both as monotherapy [18] or in combination with (ACE) inhibitors [19] has been questioned in last years. Regarding lipid-lowering drugs, a recent meta-analysis revealed no reduction in the overall mortality of women treated with statins for secondary prevention [20].…”

Section: Resultsmentioning

confidence: 99%

Polypharmacy Patterns: Unravelling Systematic Associations between Prescribed Medications

et al. 2013

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ObjectivesThe aim of this study was to demonstrate the existence of systematic associations in drug prescription that lead to the establishment of patterns of polypharmacy, and the clinical interpretation of the associations found in each pattern. MethodsA cross-sectional study was conducted based on information obtained from electronic medical records and the primary care pharmacy database in 2008. An exploratory factor analysis of drug dispensing information regarding 79,089 adult patients was performed to identify the patterns of polypharmacy. The analysis was stratified by age and sex. ResultsSeven patterns of polypharmacy were identified, which may be classified depending on the type of disease they are intended to treat: cardiovascular, depression-anxiety, acute respiratory infection (ARI), chronic obstructive pulmonary disease (COPD), rhinitis-asthma, pain, and menopause. Some of these patterns revealed a clear clinical consistency and included drugs that are prescribed together for the same clinical indication (i.e., ARI and COPD patterns). Other patterns were more complex but also clinically consistent: in the cardiovascular pattern, drugs for the treatment of known risk factors—such as hypertension or dyslipidemia—were combined with other medications for the treatment of diabetes or established cardiovascular pathology (e.g., antiplatelet agents). Almost all of the patterns included drugs for preventing or treating potential side effects of other drugs in the same pattern.ConclusionsThe present study demonstrated the existence of non-random associations in drug prescription, resulting in patterns of polypharmacy that are sound from the pharmacological and clinical viewpoints and that exist in a significant proportion of the population. This finding necessitates future longitudinal studies to confirm some of the proposed causal associations. The information discovered would further the development and/or adaptation of clinical patient guidelines to patients with multimorbidity who are taking multiple drugs.

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Section: Resultsmentioning

confidence: 99%

Polypharmacy Patterns: Unravelling Systematic Associations between Prescribed Medications

et al. 2013

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“…Data from the Randomized Aldactone Evaluation Study (RALES) revealed additional benefits of MR antagonism with spironolactone on overall mortality in patients with advanced heart failure treated with angiotensin‐converting enzyme inhibitors (ACEi) and loop diuretics . Furthermore, recent reviews suggest that dual blockade of RAAS should not be used or has limited effectiveness for treatment of hypertension, heart failure, nephropathy or other cardiovascular‐related complications. However, the benefits of combination therapies including MR blockade are scarce.…”

Section: Introductionmentioning

confidence: 99%

Angiotensin and mineralocorticoid receptor antagonism attenuates cardiac oxidative stress in angiotensin II‐infused rats

Minas

Thorwald

Conte

et al. 2015

Clin Exp Pharma Physio

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Angiotensin II (Ang II) and aldosterone contribute to hypertension, oxidative stress and cardiovascular damage, but the contributions of aldosterone during Ang II-dependent hypertension are not well defined because of the difficulty to assess each independently. To test the hypothesis that during Ang II infusion, oxidative and nitrosative damage is mediated through both the mineralocorticoid receptor (MR) and angiotensin type 1 receptor (AT1), five groups of Sprague-Dawley rats were studied: 1) control, 2) Ang II infused (80 ng/min × 28d), 3) Ang II + AT1 receptor blocker (ARB; 10 mg losartan/kg/d × 21d), 4) Ang II + mineralocorticoid receptor (MR) antagonist (Epl; 100 mg eplerenone/d × 21d) and 5) Ang II + ARB + Epl (Combo; × 21d). Both ARB and combination treatments completely alleviated the Ang II-induced hypertension, whereas eplerenone treatment only prolonged the onset of the hypertension. Eplerenone treatment exacerbated the Ang II-mediated increase in plasma and heart aldosterone 2.3- and 1.8-fold, respectively, while ARB treatment reduced both. Chronic MR blockade was sufficient to ameliorate the AT1-mediated increase in oxidative damage. All treatments normalized protein oxidation (nitrotyrosine) levels; however, only ARB and Combo treatments completely reduced lipid peroxidation (4-hydroxynonenal) to control levels. Collectively, these data suggest that receptor signaling, and not the elevated arterial blood pressure, is the principal culprit in the oxidative stress-associated cardiovascular damage in Ang II-dependent hypertension.

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“…Such an effect would have been anticipated in these individuals as the effective PRA at baseline was 0.11 ng/ml/hour. In addition, the failure of dual therapy with both an ACE inhibitor and ARB to consistently and predictably lead to meaningful reductions in blood pressure could also be similarly predicted, as the number of individuals who would have a persistently elevated effective PRA while taking either an ACE inhibitor or ARB alone, and who would respond significantly to the addition of the other agent, would be small and diluted by those who did not . However, although sound in theory, the concept of calculating an effective PRA requires further study to confirm whether this calculation, as proposed, further improves the utility of PRA in guiding antihypertensive therapy.…”

Section: Unanswered Questions and Future Directionsmentioning

confidence: 99%

Plasma Renin Activity–Guided Strategy for the Management of Hypertension

Olson¹,

DeJongh

Hough

et al. 2012

Pharmacotherapy

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Despite the wide array of antihypertensive agents and the availability of national guidelines regarding treatment for hypertension, the disease remains uncontrolled in nearly 50% of affected patients. Furthermore, the number of patients with resistant hypertension continues to increase. For patients with resistant hypertension, the American Heart Association has advocated for clinical studies to determine appropriate pharmacologic treatment strategies. One proposed strategy involves ambulatory measurement of plasma renin activity (PRA) to guide the selection of antihypertensive therapy. Patients with low PRA would be prescribed natriuretic volume-mediated therapies (e.g., diuretics and calcium channel blockers), whereas those with high PRA would receive antirenin system therapies (e.g., β-blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers). This review focuses on the principles of PRA-guided therapy, its historical development, alternative approaches to classifying patients into categories of response to antihypertensive agents, and recent data supporting the use of plasma renin activity-guided hypertension management.

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Renin Angiotensin Aldosterone System Blockade: Little to No Rationale for ACE Inhibitor and ARB Combinations

Cited by 15 publications

References 35 publications

Polypharmacy Patterns: Unravelling Systematic Associations between Prescribed Medications

Polypharmacy Patterns: Unravelling Systematic Associations between Prescribed Medications

Angiotensin and mineralocorticoid receptor antagonism attenuates cardiac oxidative stress in angiotensin II‐infused rats

Plasma Renin Activity–Guided Strategy for the Management of Hypertension

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