Recent advances in the secondary prevention of coronary heart disease

Current practice guidelines provide recommendations for the secondary prevention of coronary heart disease. Following the publication of clinical trials in recent years, this review will highlight some controversial issues: the role of angiotensin and aldosterone antagonists after acute myocardial infarction; the effects of angiotensin-converting enzyme inhibitors in patients with stable coronary heart disease and preserved left ventricular ejection fraction; high-intensity lowering of low-density lipoprotein cholesterol; use of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors in the elderly; and the targeting of high-density lipoprotein cholesterol with niacin.     

Adverse cardiorenal effects of aldosterone: is aldosterone antagonism beneficial?

Aldosterone has recently been recognized as an important factor in the development and progression of cardiorenal disease. Animal and human data suggest that aldosterone contributes importantly to several disease states. These include congestive heart failure, coronary heart disease and progression of kidney disease. Recently, the discovery that aldosterone antagonists decrease pathologic injury in the kidneys and nonepithelial tissues, such as the myocardium and endothelium, has generated great controversy regarding the actual mechanisms of benefit of these agents. The available data is reviewed and conclusions drawn regarding the relative benefits of modulating aldosterone effects in the cardiovascular system and the kidney. In particular, the authors review their effects on reductions in cardiovascular events and progression of chronic kidney disease, as well as the safety and tolerability of these agents.     

Should the aldosterone-receptor antagonist – eplerenone – be used after acute myocardial infarction with left ventricular dysfunction?

Eplerenone is a more selective aldosterone-receptor antagonist than spironolactone. Patients who had evidence of left ventricular (LV) dysfunction, were enrolled for treatment with eplerenone or placebo within 3 – 14 days of acute myocardial infarction (MI). During the mean follow-up of 16 months, the primary end point of death from any cause occurred in fewer patients in the eplerenone group than in the placebo group. The other primary end point of death from cardiovascular causes or hospitalisations for cardiovascular events also occurred to a lesser extent in the eplerenone than placebo group. Eplerenone should probably be added to the optimal therapy for use after acute MI with LV dysfunction, provided care is taken to avoid hyperkalaemia.     

Eplerenone for the treatment of cardiovascular disorders

The clinical utility and ultimately guideline recommendations for aldosterone receptor-blocking agents in cardiovascular disorders is clearly mentioned by a number of major clinical outcome trials. This article reviews the pharmacology, clinical efficacy and safety of the two currently available receptor blocking agents: spironolactone and eplerenone. The potential utility of eplerenone and other mineralocorticoid receptor agents beyond current clinical indications will also be examined.     

Pathophysiological roles of aldosterone and mineralocorticoid receptor in the kidney

Aldosterone, a steroid hormone, has traditionally been viewed as a key regulator of fluid and electrolyte homeostasis, as well as blood pressure, through the activation of mineralocorticoid receptor (MR). However, a number of studies performed in the last decade have revealed an important role of aldosterone/MR in the pathogenesis of renal injury. Aldosterone/MR-induced renal tissue injury is associated with increased renal inflammation and oxidative stress, fibrosis, mesangial cell proliferation, and podocyte injury, probably through genomic and non-genomic pathways. However, our preliminary data have indicated that acute administration of aldosterone or a selective MR antagonist, eplerenone, does not change blood pressure, heart rate, or renal blood flow. These data suggest that aldosterone/MR induces renal injury through mechanisms that are independent of acute changes in systemic and renal hemodynamics. In this review, we will briefly summarize the roles of aldosterone/MR in the pathogenesis of renal injury, focusing on the underlying mechanisms that are independent of systemic and renal hemodynamic changes.     

醛固酮对大鼠主动脉bax基因表达的影响

目的 研究醛固酮对大鼠主动脉bax基因表达的影响.方法 32只SD大鼠随机分为空白对照组、腺瘤组、腺瘤+依普利酮组和腺瘤+肼苯哒嗪组.在每只大鼠皮下埋植的微量渗透泵内注入空白溶剂或醛固酮.8周后通过免疫组化、RT-PCR和Western 印迹检测主动脉bax基因的表达.结果 与对照组相比,腺瘤组大鼠主动脉bax mRNA和蛋白表达都显著上调(P＜0.05);依普利酮能够抑制醛固酮对bax基因的诱导作用(P＜0.05);而肼苯哒嗪虽然可以使大鼠收缩压下降,但不能阻止醛固酮对bax基因的作用.结论 醛固酮通过诱导bax基因表达,调节血管平滑肌细胞凋亡和干预细胞周期进程,可能是其导致血管重构的机制之一.     

Use and side-effect profile of spironolactone in a private cardiologist's practice

BACKGROUND: The beneficial effects of spironolactone on the treatment of cardiovascular diseases are well known, but translating these benefits into private practice can be difficult because of the drug's side-effect profile. HYPOTHESIS: When patients are monitored over the long term, spironolactone can be used safely with an acceptable side-effect profile. METHODS: We retrospectively studied 762 patients taking spironolactone over a 7-year period in a cardiologist's referral-based practice and monitored them for side effects from the medication. RESULTS: Data were available on 762 patients. The average age of our patients when started on the medication was 67.2 +/- 0.5 years. Of these, 585 (76.8%) patients were treated for heart failure and 155 (20.3%) for hypertension. An average dose of 38.4 +/- 1.4 mg of spironolactone was used for treatment of all conditions. Of the 762 patients, 81 (10.6%) experienced side effects while using the medication; 40 had hyperkalemia (5.3%), 14 had gynecomastia (1.8%), and 15 had gastritis (2%). Of the patients with hyperkalemia, average creatinine clearance decreased from 64.6 +/- 5.8 ml/min at therapy start to 50.3 +/- 5.5 ml/min at the time of onset of side effects. CONCLUSION: Spironolactone can be used with an acceptable side-effect profile as long as patients are monitored long-term while receiving the medication.     

Eplerenone: the evidence for its place in the treatment of heart failure after myocardial infarction

INTRODUCTION: Heart failure is a frequent complication after acute myocardial infarction (MI) and carries a poor prognosis. Current treatments inhibit the renin-angiotensin-aldosterone system but suppression of aldosterone may be incomplete. The aldosterone antagonist spironolactone has been shown to improve survival in patients with chronic, severe heart failure. Eplerenone is a selective aldosterone antagonist expected to have a lower incidence of hormonal side effects than spironolactone. AIMS: To assess the evidence on the therapeutic value of eplerenone for treatment of heart failure in adults. EVIDENCE REVIEW: The evidence base consists of one large double-blind placebo-controlled multicenter randomized trial in over 6000 patients with postmyocardial infarction (MI) heart failure, comparing eplerenone plus standard therapy with placebo plus standard therapy. All the main outcomes were patient-oriented. Evidence from this trial shows that eplerenone improves survival and reduces cardiovascular hospitalization/mortality, compared with standard treatment alone. The incidence of hormonal side effects is no greater than with placebo. The risk of hyperkalemia is significantly increased, especially in patients with low creatinine clearance. Eplerenone was both more effective and more costly than standard treatment alone. The cost-effectiveness ratio has been estimated at $US10 402-21 876 per life-year gained. PLACE IN THERAPY: Eplerenone reduces mortality compared with current treatment alone in patients with post-MI heart failure, at additional cost. Direct comparative evidence is needed to assess its efficacy versus spironolactone. It may be valuable in patients who are intolerant to the hormonal side effects of spironolactone.