Vark LC, Bertrand M, Akkerhuis KM, et al. 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: 15.2). 04/2012; 33(16):2088-97. DOI: 10.1093/eurheartj/ehs075
Source: PubMed


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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    • "The renin-angiotensin system (RAS) plays important roles in the regulation of electrolytes, blood pressure (BP), and atherosclerosis [1]. Renin catalyzes the first and rate limiting step of the cascade, the conversion of angiotensinogen to angiotensin I [2]. Genetic variants of this system have been developed to test their association with cardiovascular and renal condition [3]. "
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    ABSTRACT: Renin catalyzes the cleavage of angiotensinogen into angiotensin I. Genetic variant C-5312T of renin enhancer has been reported to increase in vitro renin gene transcription. However, no obvious in vivo study was performed to see the renin level in C-5312T when treated with angiotensin receptor blockers (ARB). Therefore, this study aimed to investigate the serum renin level and blood pressure response in ARB treated hypertensive patients. Single nucleotide polymorphism (SNP) of C-5312T was identified in 55 hypertensive patients by using multiplex PCR and renin serum level was assayed by ELISA. The data showed that the increase of serum renin levels after 5 months of ARB treatment was significantly higher in patients with CT/TT genotype (10 pg/mL) than those with CC genotype (4.08 pg/mL) ( P = 0.025). Hypertensive patients with CT/TT genotypes also showed less diastolic pressure reduction than CC genotypes in hypertensive patients with valsartan treatment ( P = 0.04) or telmisartan treatment ( P = 0.03). Finally, these findings suggested that SNP of C-5312T REN enhancer might contribute to higher increased renin serum levels and less diastolic blood pressure response to ARB treatment.
    International Journal of Hypertension 10/2015; 2015(1):930631. DOI:10.1155/2015/930631
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    • "Evidence has been provided that there is an increased risk of renal dysfunction and hyperkalemia, with limited additive efficacy.79 In a recent meta-analysis, all-cause mortality reduction in hypertensive patients was driven primarily by ACEIs compared to ARBs.80 Relevant side effects are displayed in Table 3. "
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    ABSTRACT: Treatment of hypertension in the elderly is expected to become more complex in the coming decades. Based on the current landscape of clinical trials, guideline recommendations remain inconclusive. The present review discusses the latest evidence derived from studies available in 2013 and investigates optimal blood pressure (BP) and preferred treatment substances. Three common archetypes are discussed that hamper the treatment of hypertension in the very elderly. In addition, this paper presents the current recommendations of the NICE 2011, JNC7 2013-update, ESH/ESC 2013, CHEP 2013, JNC8 and ASH/ISH guidelines for elderly patients. Advantages of the six main substance classes, namely diuretics, beta-blockers (BBs), calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and direct renin inhibitors (DRIs) are discussed. Medical and economic implications of drug administration in the very elderly are presented. Avoidance of treatment-related adverse effects has become increasingly relevant. Current substance classes are equally effective, with similar effects on cardiovascular outcomes. Selection of substances should therefore also be based on collateral advantages of drugs that extend beyond BP reduction. The combination of ACEIs and diuretics appears to be favorable in managing systolic/diastolic hypertension. Diuretics are a preferred and cheap combination drug, and the combination with CCBs is recommended for patients with isolated systolic hypertension. ACEIs and CCBs are favorable for patients with dementia, while CCBs and ARBs imply substantial cost savings due to high adherence.
    Clinical Interventions in Aging 03/2014; 9:459-475. DOI:10.2147/CIA.S40154 · 2.08 Impact Factor
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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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