Article

Angiotensin-converting enzyme inhibitors reduce mortality in hypertension: A meta-analysis of randomized clinical trials of renin-angiotensin-aldosterone system inhibitors involving 158 998 patients

Department of Cardiology, Thoraxcenter, Erasmus MC, 's Gravendijkwal 230, 3015 GE Rotterdam, The Netherlands.
European Heart Journal (Impact Factor: 14.72). 04/2012; 33(16):2088-97. DOI: 10.1093/eurheartj/ehs075
Source: PubMed

ABSTRACT Renin-angiotensin-aldosterone system (RAAS) inhibitors are well established for the reduction in cardiovascular morbidity, but their impact on all-cause mortality in hypertensive patients is uncertain. Our objective was to analyse the effects of RAAS inhibitors as a class of drugs, as well as of angiotensin-converting enzyme (ACE) inhibitors and AT1 receptor blockers (ARBs) separately, on all-cause mortality.
We performed a pooled analysis of 20 cardiovascular morbidity-mortality trials. In each trial at least two-thirds of the patients had to be diagnosed with hypertension, according to the trial-specific definition, and randomized to treatment with an RAAS inhibitor or control treatment. The cohort included 158 998 patients (71 401 RAAS inhibitor; 87 597 control). The incidence of all-cause death was 20.9 and 23.3 per 1000 patient-years in patients randomized to RAAS inhibition and controls, respectively. Overall, RAAS inhibition was associated with a 5% reduction in all-cause mortality (HR: 0.95, 95% CI: 0.91-1.00, P= 0.032), and a 7% reduction in cardiovascular mortality (HR: 0.93, 95% CI: 0.88-0.99, P= 0.018). The observed treatment effect resulted entirely from the class of ACE inhibitors, which were associated with a significant 10% reduction in all-cause mortality (HR: 0.90, 95% CI: 0.84-0.97, P= 0.004), whereas no mortality reduction could be demonstrated with ARB treatment (HR: 0.99, 95% CI: 0.94-1.04, P= 0.683). This difference in treatment effect between ACE inhibitors and ARBs on all-cause mortality was statistically significant (P-value for heterogeneity 0.036).
In patients with hypertension, treatment with an ACE inhibitor results in a significant further reduction in all-cause mortality. Because of the high prevalence of hypertension, the widespread use of ACE inhibitors may result in an important gain in lives saved.

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Available from: Jasper J Brugts, Mar 29, 2014
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    • "Furthermore, ACE inactivates bradykinin, a peptide that induces vasodilation [4]. Because of these negative roles, ACE inhibitors were designed to target the ACE active site [5], and these inhibitors have been used as antihypertensive agents clinically [6]. Angiotensin receptor blockers (ARBs) were introduced later, as an attempt to target specific sub-effects of ACE. "
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    • "Furthermore, ACE inactivates bradykinin, a peptide that induces vasodilation [4]. Because of these negative roles, ACE inhibitors were designed to target the ACE active site [5], and these inhibitors have been used as antihypertensive agents clinically [6]. Angiotensin receptor blockers (ARBs) were introduced later, as an attempt to target specific sub-effects of ACE. "
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    ABSTRACT: Angiotensin converting enzyme (ACE) is well-known as a Zn metalloprotease that converts angiotensin-I to angiotensin-II. Since the 1970's, ACE inhibitors have been designed to target the ACE active site and have clinically been used as anti-hypertension drugs. Several ACE inhibitors have also been documented to prevent remodeling of the extracellular matrix (ECM) in the setting of myocardial infarction (MI), but it is not clear whether the entirety of this effect is due to angiotensin-II inhibiting functions. Matrix metalloproteinase (MMP)-9, also a Zn dependent protease, is known as one of the key effectors of ECM remodeling, and has a substrate specificity portfolio that is significantly different from ACE. MMP-9 digests type IV collagen as well as several inflammatory proteins. MMP-9 levels increase after MI in humans and animal models, and cardiac dysfunction and mortality after MI are suppressed by MMP-9 inhibitors and in MMP-9 null mice. In addition, recent reports that ACE inhibitors inhibit MMP-9 in an in vitro assay system and in infarcted left ventricles led us to postulate direct interactions between ACE inhibitors and MMP-9. In this review article, we will discuss the molecular
    ACE Inhibitors: Medical Uses, Mechanisms of Action, Potential Adverse Effects and Related Topics. Volume 1, 10/2013: chapter Molecular Mechanisms and Pharmacological Implications of MMP-9 Inhibition by ACE Inhibitors: pages 179-198 ((( This chapter will be an Open Access article available from Nova website - https://www.novapublishers.com - in 2013. If you want to read it, please try to search my name from "Quick Find" on this site! ))); Nova Science Publishers, Inc.., ISBN: 978-1-62948-383-2
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    • "This led to the discovery of captopril, the first orally active ACE inhibitor (ACEi) [7], followed by the prodrugs such as enalapril and ramipril [8]. ACE inhibition now forms an important cornerstone in the management of hypertension with recent data showing a potential reduction in all-cause mortality by ACE inhibition [9]. "
    ACE Inhibitors in Medicine, Uses, Mechanisms of Action and Potential Adverse Effects., 01/2013: chapter Basis of ACE inhibition in the treatment of infantile haemangioma.; Nova Publishers Inc.
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