Prevention of atrial fibrillation with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: a meta-analysis

OBJECTIVES: This study was designed to identify all randomized clinical trial data evaluating angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for the prevention of atrial fibrillation (AF), to estimate the magnitude of this effect and to identify patient subgroups most likely to benefit. BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) reduce morbidity and mortality in patients with heart failure, vascular disease, and hypertension. Several reports suggest that they may also prevent the development of AF. METHODS: A systematic review of the literature was performed to identify all reports of the effect of ACEIs or ARBs on the development of AF. Eligible studies had to be randomized, controlled, parallel-design human trials of an ACEI or ARB that collected data on the development of AF. RESULTS: A total of 11 studies, which included 56,308 patients, were identified: 4 in heart failure, 3 in hypertension, 2 in patients following cardioversion for AF, and 2 in patients following myocardial infarction. Overall, ACEIs and ARBs reduced the relative risk of AF by 28% (95% confidence interval [CI] 15% to 40%, p = 0.0002). Reduction in AF was similar between the two classes of drugs (ACEI: 28%, p = 0.01; ARB: 29%, p = 0.00002) and was greatest in patients with heart failure (relative risk reduction [RRR] = 44%, p = 0.007). Overall, there was no significant reduction in AF in patients with hypertension (RRR = 12%, p = 0.4), although one trial found a significant 29% reduction in patients with left ventricular (LV) hypertrophy. In patients following cardioversion, there appears to be a large effect (48% RRR), but the confidence limits are wide (95% CI 21% to 65%). CONCLUSIONS: Both ACEIs and ARBs appear to be effective in the prevention of AF. This benefit appears to be limited to patients with systolic left ventricular dysfunction or LV hypertrophy. The use of these drugs following cardioversion appears promising but requires further study.     

Role of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in the management of atrial fibrillation

Atrial fibrillation (AF) is the most common clinical arrhythmia, and is difficult to treat. Current treatment strategies are far from optimal. Antiarrhythmic drug therapy to maintain sinus rhythm is limited by inadequate efficacy and potentially serious side effects. New areas of research include targeting the AF substrate and examining whether drugs can produce atrial structural and/or electrophysiological remodelling, and whether this results in a reduction in AF burden. There are two approaches to the treatment of AF. The first approach is cardioversion and treatment with antiarrhythmic drugs to maintain sinus rhythm. The other approach is the use of rate-controlling drugs allowing AF to persist. In both approaches, the use of anticoagulant drugs is recommended. There is an increasing interest in novel therapeutic approaches that target AF-substrate development. Recent trials suggest that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor II blockers (ARBs) may be useful, particularly in patients with left ventricular hypertrophy, hypertension, chronic heart failure and left ventricular dysfunction. While experimental studies have shown that the pathogenic structural and electrical remodelling of the atria are prevented by inhibition of angiotensin II, the clinical potential and mechanisms of this approach are still under active investigation. The present article will discuss information pertaining to the mechanism of action and clinical use of ACEIs and ARBs in AF. It will also review the current data on the use of ACEIs and ARBs in a high-risk group of AF patients (heart failure, hypertensive with left ventricular hypertrophy, and myocardial infarction), together with the potential benefit of this class type of pharmacological therapy in direct current cardioversion and after radiofrequency catheter ablation.     

房颤的非离子通道药物治疗:ACEI和ARB

临床和实验研究都已证明,肾素-血管紧张素-醛固酮系统(RAAS)在房颤的发生和发展中起关键作用.血管紧张素Ⅱ(AngⅡ)介导心房颤动的形态学底物心房间质纤维化的形成,抑制AngⅡ可以逆转心房颤动时心房重构的发生.血管紧张素转换酶抑制剂(ACEI)和血管紧张素Ⅱ受体阻断剂(ARB)通过对RAAS的干预,阻断AngⅡ介导心房纤维化的特异性信号转导通路,从而阻断心房重构的进程,预防或减少心房颤动的发生,有望成为未来心房颤动的非离子通道药物治疗处理策略.     

Use of beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers to prevent atrial fibrillation

Atrial fibrillation, the most common cardiac arrhythmia in clinical practice, causes significant burden to patients and health care systems worldwide. Attention is being paid to prevention of atrial fibrillation using drugs that retard or prevent atrial.brosis and arrhythmogenic remodeling, which lead to this arrhythmia. Agents that work through the renin-angiotensin-receptor system, the angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, are showing promise in animal and human studies.     

Angiotensin converting enzyme inhibitors and angiotensin II receptor blockers in atrial fibrillation

Atrial fibrillation is the most prevalent clinically relevant arrhythmia; a major cause of morbidity and hospitalization. Additionally, atrial fibrillation carries a significant risk of thrombo-embolic events, specifically cerebrovascular accident. Among the most prevalent risk factors for atrial fibrillation, hypertension not only has the strongest correlation but is also the most prevalent. The renin-angiotensin-aldosterone system represents a prime target for the treatment of hypertension through the use of angiotensin-converting enzymes inhibitors and angiotensin II receptor blockers. In addition to blood pressure control, these medications have been shown to reduce the occurrence of atrial fibrillation. They have been shown to have effects at the cellular level in preventing atrial fibrosis. Additionally, these medications may prevent the development ofatrial fibrillation, reduce the duration of atrial fibrillation, and facilitate electrical cardioversion in patients with the arrhythmia. Therefore, patients with, or at risk for atrial fibrillation may benefit from treatment with renin-angiotensin-aldosterone system antagonists; deriving benefits from these medications beyond simple blood pressure control.     

Comparative effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on blood pressure and the kidney

Many clinicians are uncomfortable about using angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type 1 receptor blockers (AT(1)-blockers) to treat patients with renal disease because of concerns about increasing serum creatinine levels. However, the benefits of these medications, particularly their efficacy in slowing the progression of renal disease, outweigh such concerns. ACE inhibitors are effective in patients with type 1 diabetes and renal disease, as well as in those with nondiabetic renal disease and proteinuria >0.5 g/d. AT(1)-blockers slow the progression of diabetic nephropathy in patients with type 2 diabetes. Although these classes of medications should not be used in patients with severe renal insufficiency (e.g., glomerular filtration rate <20 mL/min), they may be beneficial in patients with mild-to-moderate renal insufficiency. Nonetheless, caution should be exercised in those with a glomerular filtration rate <30 mL/min, and serum creatinine and potassium levels should be checked approximately 1 week after starting treatment. There is also evidence suggesting that these medications lead to greater reductions in blood pressure and proteinuria when used in combination than when alone. The purpose of this paper is to review the mechanisms of action of these two classes of medication, as well as the experimental and clinical evidence that they slow the progression of renal disease.     

Hyperkalemia associated with use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers

The aims of this article are to review the current understanding of hyperkalemia associated with angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) therapy. This includes reviewing the pathophysiology of how these agents affect potassium handling within the kidney, risk factors for developing hyperkalemia, incidence, clinical signs and symptoms, and providing a practical approach to treatment of the patient who is either at risk of, or experiencing, hyperkalemia. ACEi and ARB are effective therapeutic agents used in a variety of clinical scenarios. However, related to their effects on the renin-angiotensin-aldosterone system, their use can be associated with hyperkalemia, particularly in patients who have chronic renal insufficiency. Published incidence estimates of hyperkalemia associated with ACEi or ARB vary, but up to 10% of patients may experience at least mild hyperkalemia. Important considerations when initiating ACEi or ARB therapy include obtaining an estimate of glomerular filtration rate and a baseline serum potassium concentration, as well as assessing whether the patient has excessive potassium intake from diet, supplements, or drugs that can also increase serum potassium. Serum potassium monitoring shortly after initiation of therapy can assist in preventing hyperkalemia. If hyperkalemia does develop, prompt recognition of cardiac dysrhythmias and effective treatment to antagonize the cardiac effects of potassium, redistribute potassium into cells, and remove excess potassium from the body is important.Understanding the mechanism of action of ACEi and ARB coupled with judicious drug use and clinical vigilance can minimize the risk to the patient of developing hyperkalemia. Should hyperkalemia occur, prompt recognition and management can optimize clinical outcome.     

心房颤动患者心房组织血管紧张素Ⅱ受体表达及血管紧张素转换酶抑制剂干预的初步研究

目的探讨心房颤动(房颤)患者心房组织血管紧张素Ⅱ(AngⅡ)受体基因转录和蛋白表达的变化以及血管紧张素转换酶抑制剂(ACEI)干预的影响。方法45例心脏外科手术患者,其中窦性心律和房颤患者各12例,应用低剂量ACEI的窦性心律和房颤患者分别为9例和12例。取右心耳组织通过逆转录聚合酶链反应和免疫组织化学技术测量血管紧张素Ⅱ1型受体(AT1)和血管紧张素Ⅱ2型受体(AT2)mRNA和蛋白的相对表达量。结果窦性心律和房颤患者之间的心房组织AT1和AT2mRNA表达量差异无统计学意义;房颤患者心房组织AT1蛋白表达量明显低于窦性心律患者(2.63±1.00vs4.64±1.48,P<0.001),AT2蛋白表达量明显高于窦性心律患者(6.20±2.17vs3.72±0.88,P<0.05);应用低剂量ACEI的窦性心律和房颤患者分别与未应用ACEI的窦性心律和房颤患者相比,AT1和AT2的mRNA和蛋白表达量差异无统计学意义。结论房颤时AT1蛋白表达下调,AT2蛋白表达上调,相应的mRNA表达水平差异无统计学意义,提示肾素血管紧张素系统参与了房颤的心房结构重构;低剂量ACEI不能逆转房颤AngⅡ受体重构。     

Comparison of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in the primary prevention of myocardial infarction in hypertensive patients

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have slightly different mechanisms of action. As such, it has been hypothesized that these 2 classes of medications differ in their ability to prevent myocardial infarction. In the present case-control study, we found no difference between angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in the primary prevention of nonfatal myocardial infarction among patients with hypertension.     

A cost-effectiveness analysis of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in diabetic nephropathy

The aim of this study was to estimate the cost-effectiveness of renin-angiotensin-aldosterone system blockers in patients with diabetic nephropathy. A cost-effectiveness analysis was performed based on a meta-analysis of studies investigating the effect of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) as part of a treatment regimen on the incidence of end-stage renal disease (ESRD) in patients with diabetic nephropathy. The primary outcome was the cost to prevent 1 patient from developing ESRD. Cost analysis was performed from a third-party payer perspective in 2006 US dollars. As part of a treatment regimen, ARBs significantly reduced the incidence of ESRD and doubling of serum creatinine concentration (P<.05) but not total mortality. The cost to prevent 1 patient from developing ESRD was $31,729 (95% confidence interval, $19,443-$85,442; P<.01), $189,190 (P=.13) and $51,585 (P=.068) for patients receiving ARBs, ACE inhibitors, or either of them, respectively. This study demonstrates that blocking the RAAS, which delays the progression to ESRD, appears to be cost-effective. The current analysis favors ARBs in terms of cost-effectiveness.     

Hypertension mega-trials with cardiovascular end points: effect of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers

Background

The renin-angiotensin-aldosterone system has a pivotal role in the short- and long-term regulation of blood pressure through its principal mediator, angiotensin II. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II-receptor blockers (ARBs) decrease the deleterious effects of angiotensin II on the vasculature and heart, but have different mechanisms of action. Although the blood pressure-lowering effect of ACE inhibitors and ARBs is equivalent to that of most other antihypertensive agents, emerging data suggest that these drug classes may have a greater effect on decreasing cardiovascular morbidity and mortality rates in specific patient populations.

Methods

We reviewed large (approximately ≥5000 patients) hypertension clinical trials using ACE inhibitors and ARBs and with cardiovascular morbidity/mortality end points.

Results

Six trials of ACE inhibitors and 5 trials of ARBs (3 completed, 2 ongoing) were selected for this analysis. Data from these hypertension mega-trials suggest that ACE inhibitors and ARBs may decrease cardiovascular morbidity and mortality rates, especially in patients with diabetes mellitus, renal dysfunction, and left ventricular hypertrophy. However, some trials showed important blood-pressure differences and are therefore partly inconclusive for particular drug effects.

Conclusions

Analysis of recently reported and ongoing mega-trials of renin-angiotensin-aldosterone system inhibitors may support the notion that their vasculoprotective properties confer greater benefit by virtue of their effects beyond blood-pressure reduction. Results from trials that will be completed in the next few years may provide further support of blocking the renin-angiotensin-system in cardiovascular protection in the management of hypertension.