Benefits Of Angiotensin-converting Enzyme Inhibitors Research Articles

Abstract 19292: The Efficacy of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Patients with Coronary Artery Disease and No Heart Failure in the Modern Statin Era: a Meta-Analysis of Randomized-Controlled Trials

Background: Data from randomized-controlled trials regarding the efficacy of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) in patients with coronary artery disease (CAD) but no evidence of heart failure are inconclusive. Current ACC/AHA guidelines support their use in this population. The variation in efficacy of ACEi and ARBs in improving cardiovascular (CV) outcomes may be related to the rising use of statin therapy in the past two decades. Methods: We conducted literature review of randomized-controlled trials with ACEi or ARBs as the single intervention, focusing on studies involving patients with CAD including patients with left ventricular dysfunction but no clinical symptoms of heart failure. The MEDLINE database was searched for publications between 1/1/1980 and 12/31/2012 with searched terms including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, coronary artery disease, cardiovascular events, and myocardial infarction. Of the 1553 potentially relevant publications, 19 (14 ACEi and 5 ARB) met the inclusion criteria for a total of 99,631 randomized patients followed for a mean of 38 months. We evaluated the endpoints of CV mortality, all-cause mortality, non-fatal MI, and stroke. The relationship between endpoints across the 19 trials and the percentage of patients on statins in each trial (with available data) were evaluated using meta-regression analysis, expressed as highest standardized regression coefficient, Beta. Results: ACEi and ARB therapy across the 19 trials was associated with decreased CV mortality (OR 0.85; 95% CI 0.78-0.93) and all-cause mortality (OR 0.92; 95% CI 0.86-0.98). When adjusted for the percentage of statin, 46% of patients in the cohort, there was a significant linear decrease in the odds of CV mortality reduction with ACEi and ARB therapy (Beta = 0.01; p = 0.034). Conclusion: In patients with CAD and no evidence of heart failure, the additive benefits of ACEi and ARBs in decreasing CV mortality are blunted by statin therapy. The exact mechanism(s) for this result is unclear and further investigation is warranted. The modification of current ACC/AHA practice guidelines should be considered.

SAFETY OF PREOPERATIVE USE OF ANGIOTENSIN-CONVERTING ENZYME INHIBITORS AND ANGIOTENSIN RECEPTOR BLOCKERS IN PATIENTS UNDERGOING CARDIAC SURGERY: A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE

Although the long-term benefits of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) in myocardial infarction and heart failure have been repeatedly proven, reports concerning their continuation in patients scheduled for cardiac surgery have produced conflicting results. The purpose of this meta-analysis was to assess the impact of preoperative ACEI/ARB on short term outcomes following cardiac surgery. We performed a meta-analysis of articles comparing preoperative ACEI/ARB with no ACEI/ARB in patients undergoing cardiac surgery. The EMBASE, MEDLINE and CENTRAL databases were searched until the first week of October 2013. Two reviewers performed independent article review and study quality assessment. Data on atrial fibrillation, vasopressor requirements, acute kidney injury and mortality all occurring in the first month following surgery were collected. Since most included studies were retrospective, the generic inverse variance method was used to analyse adjusted odds ratios, calculating pooled odds ratios (ORs) and associated 95% confidence intervals (CIs) using a random effects model. We retrieved 24 studies (2 randomized trials, 20 cohort studies and 2 case-control studies) enrolling a total of 52 378 patients. Preoperative administration of ACEI/ARB significantly increased postoperative atrial fibrillation (OR: 1.15; 95% CI: 1.01 - 1.31) and vasopressor requirements (OR: 1.65; 95% CI: 1.25 - 2.22). However, no differences in mortality (OR: 0.96; 95% CI: 0.8 - 1.16) or acute kidney injury (OR: 1.05; 95% CI: 0.86 - 1.26) were observed. Preoperative use of ACEI or ARB is potentially associated with an increased risk of adverse events following heart surgery, including atrial fibrillation and greater vasopressor requirements. Large randomized trials are required to confirm these findings.

Brain-Penetrating Angiotensin-Converting Enzyme Inhibitors and Cognitive Change in Patients with Dementia due to Alzheimer's Disease

Controversy over benefits of angiotensin-converting enzyme inhibitors (ACEIs) for treatment of dementia due to Alzheimer's disease (AD) led to this alternative investigational approach by the employment of pharmacogenetic methods, correlating the cognitive change of patients with late-onset AD with the presence of common ACE gene promoter polymorphisms, and stratifying the sample in groups of patients who responded or not to the brain-penetrating ACEIs Captopril or Perindopril. A trend was found for treatment with brain-penetrating ACEIs to slow cognitive decline in AD patients with the haplotype rs1800764 (CC): rs4291 (TT) (p = 0.024), and also non-significantly for independent carriers of rs1800764 or rs4291.

Which patients should be on renin-angiotensin system blockers after coronary surgery?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'which patients should be on renin-angiotensin system blockers after coronary surgery?' Using the reported search, 12 papers represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The 12 studies included 5 prospective randomized controlled trials (RCTs) and 1 meta-analysis. One RCT of 2553 stable patients post-coronary artery bypass surgery (CABG) with left ventricular (LV) ejection fraction ≤40% showed that angiotensin-converting enzyme inhibition (ACEI) therapy can and probably should be delayed beyond 7 days due to increased cardiovascular morbidity and mortality associated with immediate postoperative initiation of ACEI treatment. Another study showed that the cardioprotective benefits of ACEI following CABG are persistent with respect to an LV ejection fraction below or above 40% and whether percutaneous coronary intervention (PCI) or CABG was performed. A large multicentre international study of 4224 patients undergoing CABG looking at a composite outcome of rates of cardiac, cerebral and renal events and in-hospital mortality showed that continuous treatment with ACEI compared with no ACEI was associated with reductions of risks of non-fatal events (P = 0.009, odds ratio 0.69, 95% confidence interval 0.52-0.91). Addition of ACEI de novo following surgery was also associated with significant reduction in the risk of the composite outcome (P = 0.004) and of a cardiovascular event (P = 0.04). We conclude that angiotensin-converting enzyme inhibitor treatment plays an important role in minimizing ischaemic events after CABG even in low-risk patients. The cardioprotective benefits of these drugs are persistent at mid- and long-term follow-up, with respect to LV ejection fraction below or above 40% and whether PCI or CABG was performed. Not only continuation of angiotensin-converting enzyme inhibition early after surgery but also adding ACEI de novo postoperatively can be associated with better cardiovascular and renal outcomes.

Cardiovascular protection by -blockade in hypertensive haemodialysis patients: the Hypertension in Haemodialysis Patients Treated With Atenolol or Lisinopril (HDPAL) trial

In the pioneer years of chronic haemodialysis (HD), hypertension was recognized as the main undisputable cause of death in end-stage kidney disease (ESKD) patients [1]. Nearly a halfcentury later, sparse data in various countries indicate that control of hypertension in the HD population still remains a major unmet clinical need worldwide. In the USA, the prevalence of hypertension exceeds 80% [2], in Great Britain it is about 50% [3] and in Italy about 70% [4]. Progress in this area has been in part hindered by the ‘reverse epidemiology’ scenario that characterizes the HD population. Uncertainty about blood pressure (BP) targets and methods of measurement is such that the Renal Association guidelines cautiously state that ‘It would be sensible to avoid sustained BP extremes and, in order to try to provide some guidance, we suggest that systolic blood pressure during the interdialytic period on HD and for peritoneal dialysis (PD) patients should not regularly exceed >160 mmHg’ [3]. Low pre-dialysis BP rather than high BP is associated with death risk. Furthermore, in sharp contrast to a large meta-analysis in individuals in the general population without a background of cardiovascular events [5], the pre-dialysis relationship between BP and death risk in end-stage kidney disease (ESKD) is definitely non-linear [6]. However, peri-dialytic BP measurements are inherently inadequate metrics of the BP burden because measurements before dialysis overestimate the underlying average BP while post-dialysis BP underestimates the same parameter. In studies applying ambulatory blood pressure monitoring (ABPM) in the HD population without severe heart failure, the link between BP and clinical outcomes is comparable with that registered in the general population with the same technique [7]. Indeed, high average ambulatory systolic pressure [8] and nocturnal systolic hypertension [9] during the dialysis intervals are strong death predictors in HD patients. Notwithstanding the public health relevance of the problem and the peculiar risk profile of the ESKD population, the number of randomized, controlled trials (RCTs) testing antihypertensive drugs in dialysis patients is very limited indeed. A meta-analysis performed in 2009 [10] identified only eight randomized trials. Of these, one was performed in patients on peritoneal dialysis, two dealt with normotensive or hypotensive patients affected by left ventricular systolic dysfunction or heart failure and another trial (FOSIDIAL) selected patients with left ventricular hypertrophy (LVH), independent of BP [11]. After this meta-analysis, the OCTOPUS trial was published [12]. Thus, we have just four relatively small RCTs specifically focusing on drug treatment of hypertension in HD patients without severe heart failure (NYHA class III or IV) (Fig. 1). Of these trials, one tested a calcium antagonist (amlodipine) [13] and three various angiotensin II receptor blockers (ARBs): candesartan in the first [14]; candesartan, losartan or valsartan in the second [15] and olmesartan in the third [12]). In trials testing ARBs, the antihypertensive effect of these drugs was comparable with that achieved by other drugs. Nonetheless, of these three trials, two documented a reduction in the risk of cardiovascular events (−47% [3] and −71% [4]). If we consider also the FOSIDIAL trial where about half of the patients were hypertensive, the combined analysis (random-effects) of trials based on ARBs and angiotensin-converting enzyme inhibitors (ACEi) shows a 31% risk reduction [RR: 0.69, 95% confidence interval (95% CI) 0.45–1.05, P = 0.086], which just fails to achieve statistical significance. Because BP in patients randomized to ACEi or ARBs in these trials was almost identical to that in patients randomized to other drugs, the apparent benefit of ACEi or ARBS appears attributable to the interference with angiotensin II effects on the cardiovascular system beyond vasoconstriction. These results are similar to those of a recent meta-analysis reporting a substantial, BP-independent, benefit of ACEi and ARBs in over 100 000 high-risk patients without heart failure [16] most of whom were hypertensive. IN F O C U S

Préservation de la fonction rénale résiduelle en dialyse

There are evidences supporting a positive impact of renal residual function (RRF) on survival and quality of life of dialysis patients. Many strategies are available in clinical practices to maintain RRF. Hemodiafiltration seems to be better that conventional hemodialysis and similar to peritoneal dialysis. Arterial hypotension in hemodialysis or dehydration in peritoneal dialysis are deleterious in terms of preservation of RRF. Loop diuretics increase urine volume and natriuresis, not RRF. Radiocontrast and aminoglycosides may be used safely. The benefits of ACE inhibitors and angiotensin II receptor blockers are debated but have positive effect on blood pressure control and cardiac function. Neither biocompatible solutions nor the modality of peritoneal dialysis have demonstrated benefits on RRF.

Genetic variation-optimized treatment benefit of angiotensin-converting enzyme inhibitors in patients with stable coronary artery disease

The objective of this study was to examine the relationship between renin-angiotensin system genotypes and the pharmacogenetics of angiotensin-converting enzyme (ACE) inhibitors in Chinese patients with coronary artery disease (CAD). Patients with angiographic CAD were recruited from 1995 to 2003. The baseline characteristics and genetic polymorphisms [ACE gene insertion/deletion (I/D) polymorphisms, six polymorphisms of the angiotensinogen (AGT) gene, and A-1166C polymorphisms of the angiotensin-II type I receptor gene (AGT1R)] were established. Patients were divided into two groups (ACE inhibitor or no ACE inhibitor) and followed for up to 12 years. Kaplan-Meier curves and Cox regression models were used to determine the survival and major cardiovascular events (MACE) event-free survival trends. Pharmacogenetic effects were determined by several Cox regression models. Of the 784 patients, 432 were treated with ACE inhibitors and 352 were not. ACE inhibitors were associated with a lower MACE rate at 4000 days. In addition, the ACE I/D gene D and AGT1R gene C alleles were associated with a higher MACE rate on the basis of a multivariate regression analysis. This effect was attenuated by the pharmacogenetic interaction of ACE inhibitors and the ACE gene (ACE inhibitors* ACE gene, hazard ratio: 0.8, 95% confidence interval: 0.62-0.94, P=0.03). ACE inhibitors were associated with a significant decrease in MACE in Chinese patients diagnosed with CAD. Genetic variants were also associated with event-free survival, but their effects were modified by the use of ACE inhibitors.

Circulation Editors' Picks

<i>Circulation</i> Editors' Picks

Effect of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Antagonists in Atherosclerosis Prevention

Atherosclerosis is a highly complex biological process that has become the scourge of modern civilization. Endothelial dysfunction is the first step in the development of atherosclerosis. The renin-angiotensin-aldosterone system (RAAS) plays an important role in the development of endothelial dysfunction and atherosclerosis. Several studies have shown that in vitro blockade of the RAAS is associated with improvement in markers of endothelial dysfunction and inflammation. Many clinical trials have demonstrated a clear benefit of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) manifested by a reduction of cardiovascular events. These findings suggest that ACEIs and ARBs can play an important role in prevention of atherosclerosis and in the delay of its progression. In this review we focus on the importance of RAAS blockade to prevent or delay progression of atherosclerosis and its impact on reduction of cardiovascular events.

Circulation: Clinical Summaries

<i>Circulation:</i> Clinical Summaries

The Primary Benefits of Angiotensin-Converting Enzyme Inhibition on Cardiac Remodeling Occur During Sleep Time in Murine Pressure Overload Hypertrophy

Our objective was to test the hypothesis that there is a significant diurnal variation for the therapeutic benefit of angiotensin-converting enzyme (ACE) inhibitors on pressure-overload cardiovascular hypertrophy. Physiological and molecular processes exhibit diurnal rhythms that may affect efficacy of disease treatment (chronotherapy). Evidence suggests that the heart primarily remodels during sleep. Although a growing body of clinical and epidemiological evidence suggests that the timing of therapy, such as ACE inhibition, alters diurnal blood pressure patterns in patients with hypertension, the benefits of chronotherapy on myocardial and vascular remodeling have not been studied. We examined the effects of the short-acting ACE inhibitor, captopril, on the structure and function of cardiovascular tissue subjected to pressure overload by transverse aortic constriction (TAC) in mice. Captopril (15 mg/kg intraperitoneally) or placebo was administered at either murine sleep time or wake time for 8 weeks starting 1 week after surgery. TAC mice given captopril at sleep time had improved cardiac function and significantly decreased heart: body weight ratios, myocyte cross-sectional areas, intramyocardial vascular medial wall thickness, and perivascular collagen versus TAC mice given captopril or placebo during wake time. Captopril induced similar drops in blood pressure at sleep or wake time, suggesting that time-of-day differences were not attributable to blood pressure changes. These beneficial effects of captopril were correlated with diurnal changes in ACE mRNA expression in the heart. The ACE inhibitor captopril benefited cardiovascular remodeling only when administered during sleep; wake-time captopril ACE inhibition was identical to that of placebo. These studies support the hypothesis that the heart (and vessels) remodel during sleep time and also illustrate the importance of diurnal timing for some cardiovascular therapies.

Imagine how many lives you save: angiotensin-converting enzyme inhibition for atherosclerotic vascular disease in the present era of risk reduction

Introduction: Angiotensin-converting enzyme (ACE) inhibition is clearly beneficial in patients with hypertension, heart failure, and post-myocardial infarction left ventricular (LV) dysfunction. However, whereas initial trials had reported a benefit of ACE inhibition in high-risk vascular patients, current trials of ACE inhibition have failed to demonstrate a clear benefit in vascular patients who are receiving risk-reduction interventions. The purpose of this review is to analyze the reasons behind the failure of the most recent trials of ACE inhibitors in vascular patients without overt LV dysfunction. The reader will gain an understanding of the time-dependent trend towards a reduction in the absolute benefit conferred by ACE inhibition in patients with vascular atherosclerosis as risk reduction interventions are increasingly implemented.Areas covered: Major trials with a follow-up period of at least 1 year assessing the use of ACE inhibitors in patients with a history of cardiac or vascular events were identified via a PubMed literature search. All-cause and cardiovascular mortality outcomes were reported for each trial, as well as the use of aspirin, lipid-lowering drugs and β-blockers, and the mean LV ejection fraction.Expert opinion: The findings of recent trials do not support the use of ACE inhibitors in vascular patients who, adherent with risk reduction therapy, do not have hypertension, diabetes, or LV dysfunction.

Modern treatment of patients at risk: still a HOPE for ACE inhibitors?

Indications for angiotensin-converting enzyme (ACE) inhibitors include heart failure, postmyocardial infarction, diabetes mellitus and proteinuric chronic renal disease. ACE inhibitors provided life-saving benefits in patients with heart failure or left ventricular systolic dysfunction. On the other hand, there are conflicting data regarding the ability of ACE inhibitors to reduce the incidence of cardiovascular events in patients with vascular disease and preserved left ventricular systolic function. Results of the main randomized clinical trials that evaluated the benefit of ACE inhibitors in patients with vascular disease are discussed in this editorial. In particular, the different prognostic impact of ACE inhibitors in high-risk patients with and without heart failure or preserved left ventricular systolic function is examined in detail. The possible impact of lipids and statins on the effect of ACE inhibitors is also discussed. In our opinion, the available data indicate that ACE inhibitors should continue to be used in all patients with documented coronary artery disease or different phenotypes of high vascular risk, even in a context of modern and aggressive preventive strategies.

Herzinsuffizienz und Komorbiditäten

Noncardiac Comorbidities are frequent and may be overlooked during routine CHF management. They have great impact on hospitalisations and mortality. The most important comorbidities in heart failure patients are renal insufficiency, diabetes mellitus, chronic obstructive pulmonary disease, sleeping disorders like obstructive and central apnea syndrom, and anemia. The most powerful predictor for mortality is renal insufficiency. It's important to recognize the different causes of renal failure. Defining the volume status and the cardiac output is crucial for the guidance of therapy. The management of diuretic resistance is of special interest and often challenging. Diabetes mellitus is an independent risk factor for heart failure. The benefit of ACE inhibitors and Angiotensin receptor blockers for HF and DM is accepted. The management of Diabetes in HF depends on side-effect profiles of the numerous anti-diabetic drugs. Metformin is safe even in HF patients. Thiazolidinediones should be avoided in NYHA class III/IV because of fluid retention. In COPD patients there is an underuse of betablockers and the prediction of mortality with this comorbidity could be partially caused by that. The principle goal of treatment of sleeping disorders is to avoid hypoxia during night. CPAP therapy improves live quality and HF symptoms. Anemia is often diagnosed, the best therapy - erythropoetin plus iron or iron alone - remains controversial. Iron supplementation without anemia could be an option for better quality of life. To handle all these comorbidities in heart failure patients becomes more and mor complex. Heart failure nurses can help us to manage these growing population.

Reviewing the benefits of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in diabetic nephropathy – are they drug specific or class specific?

Hypertension is prevalent in patients with type 2 diabetes mellitus and contributes to substantial morbidity and mortality. Preventing microalbuminuria (MAU) is important in these patients because MAU is associated with an increased risk of end-stage renal disease and cardiovascular events. Current hypertension treatment recommendations are based on drug 'class' effects. For the treatment of hypertension in patients with diabetes, important agent-specific effects should be brought into consideration in the choice of drug. For these patients, and especially in the presence of kidney disease, the choice of agent must effectively target not only blood pressure reduction, but also prevention and treatment of MAU for optimal organ outcomes. A review of the current evidence suggests a diversity of MAU-associated risk reduction according to agent within the angiotensin receptor blocker and angiotensin-converting enzyme inhibitor classes, ranging from nonefficacy to significant efficacy. Recommendations should clearly state absolute risk reduction according to agent, based on the best available evidence.

Optimal dose of angiotensin‐converting enzyme inhibitor or angiotensin II receptor blocker for renoprotection

Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB) have become the cornerstone in the treatment of chronic kidney disease (CKD), as numerous lines of evidence have shown that these agents have a blood pressure lowing independent anti-proteinuric effect. However, despite the benefits of ACEI or ARB therapy, a substantial proportion of patients still experience renal morbidity and mortality. Considering the prognostic impact of proteinuria reduction, it is currently assumed that titration of ACEI or ARB for optimal anti-proteinuric effect would be a logical step towards improvement of renoprotection. Recent published studies, performed with higher than recommended doses of either ACEI or particularly ARB, suggest that the approach is associated with a further decrement in urinary protein excretion and probably improved renal outcome. Although most patients achieve their maximum benefit at standard doses, there is a residual group of patients who may do so at higher doses of renin-angiotensin system inhibitors. Because patients who would benefit from higher doses are not identifiable a priori, a titration process might be cogent in order to provide more robust anti-proteinuric benefit to such patients.

Are We Ready to Screen the General Population for Microalbuminuria?

The United States Preventive Services Task Force does not recommend screening for proteinuria in adults[1][1]; however, this recommendation has not be reviewed since 1989 and therefore cannot take into consideration newer information on benefits of angiotensin-converting enzyme inhibitors (ACEIs) or

Digoxin

Despite more than 200 years of research, the role of digoxin in contemporary medicine remains controversial. It is an old drug but with a remarkably sophisticated and rather modern pharmacological profile. It was the first neuroendocrine modulator to enhance parasympathetic tone and possibly reduce sympathetic activity.1 It is the only available oral inotropic agent. It is probably also a diuretic.2 In common with many other agents for heart failure, good dose-ranging studies have not been conducted, and the optimal dose is uncertain. Well-designed randomized controlled trials conducted in the pre–β-blocker era suggested that digoxin could improve symptoms and exercise capacity,3,4 but a large trial that enrolled patients mostly with mild symptoms suggested no overall effect on mortality, although it did report a substantial (28%) reduction in hospitalization for worsening heart failure.5 A small increase in sudden death was balanced by a reduction in death from worsening heart failure. Whether these benefits were mediated by changes in autonomic tone, in heart rate, in sodium balance, or through inotropic effects is unclear. Article see p 90 At this time, the clinical community’s attention turned from the potential, but still equivocal, effects of digoxin on morbidity and mortality to the striking benefits of aldosterone receptor antagonists6 and β-blockers7 and, subsequently, cardiac resynchronization therapy8 on prognosis. Digoxin became largely ignored in discussions and debate, its use declined rapidly (Table⇓ and Figure), and the role of digoxin for managing heart failure was left unresolved. View this table: Table. Summary Characteristics of Landmark Trials of Heart Failure View this table: Table. Continued Figure. Plot of proportions of patients with atrial fibrillation or treated with digoxin in landmark trials of heart failure. AF, atrial fibrillation. The benefits of angiotensin-converting enzyme inhibitors, β-blockers, and aldosterone antagonists could simply be so overwhelming that any additional benefit from …

Role of Angiotensin‐Converting Enzyme Inhibitors, Angiotensin II Receptor Blockers, and Aldosterone Antagonists in the Prevention of Atrial and Ventricular Arrhythmias

Atrial arrhythmias, ventricular arrhythmias, and sudden cardiac death (SCD) are significant health problems and an economic burden to society. The renin-angiotensin-aldosterone system (RAAS) may play a key role in the occurrence of structural and electrical remodeling, potentially explaining the development of atrial and ventricular arrhythmias. Angiotensin II has been shown to regulate cardiac cell proliferation and to modulate cardiac myocyte ion channels. Results of post hoc analyses from prospective clinical trials appear to show that angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are most effective in the prevention of new-onset atrial fibrillation in patients with heart failure. It is difficult to determine if these agents are useful in the prevention of new-onset atrial fibrillation after myocardial infarction, and available evidence suggests that the benefit of ACE inhibitors and ARBs for prevention of new-onset atrial fibrillation in patients with hypertension appears limited to those with left ventricular hypertrophy. Patients with structural changes in cardiac muscle, such as those with heart failure and left ventricular hypertrophy, appear to benefit the most from RAAS blockade, possibly due to the theory of reversal of cardiac remodeling. There is no evidence, to our knowledge, that either ACE inhibitors or ARBs facilitate direct electrical current cardioversion in patients with atrial fibrillation; however, it appears that RAAS blockade may be useful in the prevention of recurrent atrial fibrillation after direct electrical current cardioversion. Whether ACE inhibitors may prevent life-threatening ventricular arrhythmias or SCD is unclear. Aldosterone antagonists appear to be useful for the prevention of SCD in patients with left ventricular systolic dysfunction. Results from ongoing clinical trials are anticipated to provide further insight on the potential roles of RAAS inhibitors for the prevention of cardiac arrhythmias.

Benefits of ACE Inhibitors in Diabetes

Angiotensin-converting enzyme (ACE) inhibitors have been FDA-approved for treating refractory hypertension since 1981. Since then, clinical investigations support the benefits of ACE inhibition (ACE-I) in pathologies like congestive heart failure, myocardial infarction, diabetes mellitus, chronic renal insufficiency, and atherosclerotic cardiovascular disease. Both, clinical trials and animal models of type I and type II diabetes have shown that hyperactivity of the angiotensin II signaling pathway contributes to the development of diabetes and its complications, and that blockade of the renin-angiotensin system prevents new onset diabetes and reduces the risk of diabetic complications. Furthermore, ACE inhibitors are generally well tolerated and have few contraindications. This article describes ACE as a target molecule and gives an overview on the clinical evidence that supports the use of ACE inhibitors in diabetes.