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A role for the renin-angiotensin-aldosterone-system in Severe Acute Respiratory Syndrome-Coronavirus-2 infection and in the development of COronaVIrus Disease-19 disease has generated remarkable concerns among physicians and patients. Even though a suggestive pathophysiological link between renin-angiotensin-aldosterone-system and the virus has been proposed, its pathogenic role remains very difficult to be defined. Although COronaVIrus Disease-19 targets preferentially older people with high prevalence of hypertension and extensive use of renin-angiotensin-aldosterone-system inhibitors, an independent role for hypertension and its therapies is not defined. In this article, we scrutinize evidence from the most representative available studies in which the potential role of renin-angiotensin system inhibitors, specifically angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, was evaluated in the COronaVIrus Disease-19 disease course, with regard to severity of the disease and mortality. We conclude that at this time, the overall available evidence fails to support a pathogenetic speaks against any harmful role for of renin-angiotensin-aldosterone-system inhibitors in COronaVIrus Disease-19. Consequently, we conclude that treatment with renin-angiotensin-aldosterone-system inhibitors should not be discontinued and, therefore, these therapies should not be interrupted. • The SARS-Cov2 utilizes the angiotensin-converting enzyme 2 to enter cells. • Renin angiotensin system inhibitors, increase angiotensin-converting enzyme II levels. • Therefore, these most common anti-hypertensive drugs might influence Covid-19. • Extensive data that has recently become available recently do not support this hypothesis. • We recommend that treatment with renin angiotensin system inhibitors should not be discontinued in Covid-19 patients. [ABSTRACT FROM AUTHOR]

Some cohort studies showed the possibility of renin-angiotensin-aldosterone system (RAAS) blockade in preventing future osteoporotic fractures. The study aimed to evaluate the association between angiotensin converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), and future osteoporotic fracture in a hypertensive population. We queried the Taiwan Longitudinal Health Insurance Database between 2001 and 2012. We used propensity score matching and the total cohort was made up of 57,470 participants (28,735 matched-pairs using or not using RAAS blockers). The mean follow-up period was 6 years. The number of incident fractures was 3757. Hazard ratios (HRs) [95% confidence interval (CI)] of ACEIs and ARBs use with incident fractures were calculated. The incidence of future osteoporotic fracture was significantly lower in the ACEI and ARB user groups but not in the group using an ACEI plus ARB concomitantly, when compared with RAAS blocker nonusers. Comparing ACEI users with RAAS blocker non-users and ARB users with RAAS blocker non-users, the HRs for composite fractures were 0.70 (0.62–0.79) and 0.58 (0.51–0.65), respectively. Sensitivity analysis confirmed a lower incidence of future osteoporotic fracture in patients taking an ACEI for >55 cumulative defined daily doses (cDDDs) and those who received an ARB for >90 cDDDs. These results suggested a lower incidence of future osteoporotic fracture in a hypertensive population who were using an ACEI or ARB compared with RAAS blocker nonusers but not in the group taking an ACEI and ARB concomitantly. • The incidence of future osteoporotic fracture was lower in the ACEI and ARB groups. • The phenomenon was not observed in the group taking an ACEI and ARB concomitantly. • A lower incidence of future osteoporotic fracture was noted if using ACEI >55 cDDDs. • A lower incidence of future osteoporotic fracture was noted if using ARB >90 cDDDs. [ABSTRACT FROM AUTHOR]

Background Diabetes Mellitus (DM) is an important factor of adverse cardiovascular events in acute ST-segment elevation myocardial infarction (STEMI) patients. Renin-angiotensin-aldosterone system (RAAS) inhibitors is associated with improved clinical outcomes, however, there are limited data comparing the effectiveness of two different RAAS inhibitors in STEMI patients with DM undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Methods A total of 3811 eligible STEMI patients with DM were enrolled in Korea Acute Myocardial Infarction Registry (KAMIR). They were stratified into two groups: Angiotensin converting enzyme inhibitors (ACEI) group (n = 2691) and angiotensin receptor blockers (ARB) group (n = 1120). To adjust baseline confounding factors, we performed propensity score matching (PSM) analysis and evaluated individual and composite major clinical outcomes between the two groups up to 2 years. Results After PSM, a total of 1049 well-matched pairs were generated. Baseline clinical, angiographic and procedural characteristics were well-balanced between the two groups. The incidence of death, recurrent myocardial infarction (MI), revascularization and major adverse cardiac events (MACE) were not significantly different between the two groups up to 2 years, Conclusion In the present study, ACEI and ARB showed comparable effectiveness and safety on individual and composite clinical outcomes in STEMI patients with DM who underwent successful PCI with DES at least up to 2 years. [ABSTRACT FROM AUTHOR]

Objective To assess the effectiveness of renin-angiotensin aldosterone system (RAAS) inhibitors to prevent all-cause and cardiovascular death, myocardial infarction and stroke in hypertensive patients considering the number needed to treat (NNT). Methods Data from a meta-analysis of 18 prospective, randomized, controlled morbidity-mortality trials (68 343 RAAS inhibitor; 84 543 control) were used to calculate NNTs for the prevention of all-cause and cardiovascular mortality, myocardial infarction, and stroke. Results Angiotensin-converting enzyme (ACE) inhibitors were used in 7 trials and angiotensin receptor blockers (ARBs) in 11 trials. Mean follow-up was 4.3 years. The annual incidence rate of all-cause mortality was 0.0233 in patients randomized to RAAS inhibitors versus 0.0252 in controls (hazard ratio 0.95, 95% confidence interval 0.91 to 0.99). The corresponding median NNT to prevent one death was 113 (2.5-97.5th percentile, 85 to 168) in favor of RAAS inhibitors, which was driven by ACE inhibitors (NNT 67, 2.5-97.5th percentile, 53 to 92) rather than ARBs (NNT 335, 2.5-97.5th percentile, - 4341 to 5076). Results for cardiovascular mortality (NNT 116 for ACE inhibitors and 409 for ARBs, respectively) and myocardial infarction (NNT 80 and 338, respectively) also appeared to be driven by ACE inhibitors. We found a lower NNT for stroke in favor of ARB (NNT 337 and 131, respectively) although this difference was statistically non-significant. Conclusion Among hypertensive patients, ACE inhibitors but not ARBs, substantially reduce all-cause and cardiovascular mortality and myocardial infarction. [ABSTRACT FROM AUTHOR]

Background Renin–angiotensin system inhibition (RASI) is frequently avoided in aortic stenosis (AS) patients because of fear of hypotension. We evaluated if RASI with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) increased mortality in patients with mild to moderate AS. Methods All patients (n = 1873) from the Simvastatin and Ezetimibe in Aortic Stenosis study: asymptomatic patients with AS and preserved left ventricular (LV) ejection fraction were included. Risks of sudden cardiac death (SCD), cardiovascular death and all-cause mortality according to RASI treatment were analyzed by multivariable time-varying Cox models and propensity score matched analyses. Results 769 (41%) patients received RASI. During a median follow-up of 4.3 ± 0.9 years, 678 patients were categorized as having severe AS, 545 underwent aortic valve replacement, 40 SCDs, 103 cardiovascular and 205 all-cause deaths occurred. RASI was not associated with SCD (HR: 1.19 [95%CI: 0.50–2.83], p = 0.694), cardiovascular (HR: 1.05 [95%CI: 0.62–1.77], p = 0.854) or all-cause mortality (HR: 0.81 [95%CI: 0.55–1.20], p = 0.281). This was confirmed in propensity matched analysis (all p > 0.05). In separate analyses, RASI was associated with larger reduction in systolic blood pressure (p = 0.001) and less progression of LV mass (p = 0.040). Conclusions RASI was not associated with SCD, cardiovascular or all-cause mortality in asymptomatic AS patients. However, RASI was associated with a potentially beneficial decrease in blood pressure and reduced LV mass progression. [ABSTRACT FROM AUTHOR]

Abstract: Background: The renin–angiotensin–aldosterone system is suggested to play a key role in the development of atrial fibrillation through structural and electrical remodeling. This review aims to assess the effectiveness of blockade of the renin–angiotensin–aldosterone system in the prevention of new onset atrial fibrillation. Methods: Electronic databases from 1984 onwards and previous systematic reviews were searched in addition to contacting experts in the field. Two reviewers independently selected eligible randomized controlled trials that reported on new onset atrial fibrillation, and that compared at least one of the following drugs: angiotensin-converting enzyme inhibitors, angiotensin II-receptor blockers, and aldosterone antagonists with conventional therapy or placebo. Results: Fourteen trials including 92,817 randomized patients met the inclusion criteria. RAAS inhibition compared with conventional therapy or placebo reduced new onset atrial fibrillation (RR=0.79; 95% CI; 0.69–0.90, p-value<0.001). ARBs showed a strong effect in the reduction of onset atrial fibrillation (RR=0.78; 95% CI: 0.66–0.92, p-value=0.009), whereas results for ACE inhibitors were not as clear but likely show no effect (RR=0.79, 95% CI: 0.62–1:00, p-value: 0.05). Aldosterone antagonists, did not appear to play a role in the prevention of new onset atrial fibrillation (RR=0.77, 95%CI: 0.55–1.08, p-value: 0.21). Risk reduction was highest among heart failure patients. Conclusions: RAAS inhibition appears to reduce the risk of developing new onset atrial fibrillation in different patient groups with coronary artery disease. Yet these results were considered of low quality evidence and therefore further research with stronger quality trials is required to confirm current results. [Copyright &y& Elsevier]

Two decades of research from CONSENSUS to CHARM using modulators of the renin–angiotensin–aldosterone system (RAAS) in chronic heart failure (CHF) patients have shown convincing clinical benefits, but the majority of clinicians prescribing these drugs are still unclear about what mechanisms are responsible for the observed benefits. Of the candidate mechanisms hitherto proposed, there emerges a theme that best fits the spectrum of known factors from pathophysiology of heart failure to how the drugs enhance longevity of patients. This concept can be summarised as follows: after the onset of heart failure, neurohormones are activated resulting in raised levels of angiotensin, aldosterone and catecholamines, which are all known cardiotoxic agents. Cumulatively over time, they are responsible for accelerated cardiomyocyte attrition, manifesting as a faster reduction of cardiac pumping reserve, leading to worsening heart failure, more neurohormonal activation, thus propagating a vicious cycle spiralling towards an earlier fatality. The vicious cycle can be interrupted by dampening the excessive neurohormonal activities, thereby minimising cardiomyocyte losses and preserving cardiac functional reserve for longer. This culminates in maintenance of a reasonable quality of life and enhanced longevity. Such a mechanistic understanding would enable clinicians to have a better perspective on how to apply data from various clinical trials involving these drugs into clinical practice, to optimise and tailor therapy to the individual patient so that each patient can gain maximal benefits. [Copyright &y& Elsevier]

Abstract: Purpose: To evaluate the association between statins, N-acetylcysteine (NAC) and angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) and postoperative atrial fibrillation (AF). Methods: A total of 590 patients undergoing coronary artery bypass and/or valve surgery were studied. An AF episode lasting >5 min during hospitalization was accepted as endpoint. Results: AF rate was 18% (n =106). Multivariable positive predictors of AF included age ≥65, left atrial diameter ≥45 mm, cross clamp time; negative predictors included use of left internal mammarian artery, NAC, and ACEIs or ARBs. Conclusions: ACEIs or ARBs and NAC is associated with low incidence of postoperative AF, however, this association was not found with statin or combined use these agents. [ABSTRACT FROM AUTHOR]

Abstract: The manuscript is a “Letter to the Editor” concerning the paper: “Ozaydin M, Dede O, Varol E, et al. Effect of renin–angiotensin aldosteron system blockers on postoperative atrial fibrillation. Int J Cardiol 2008; 127: 362–367”. [Copyright &y& Elsevier]