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Objectives: This analysis from the LUNAR (Limiting UNdertreatment of lipids in ACS with Rosuvastatin) study assessed lipid changes 1 to 4 days after onset of acute coronary syndromes (ACS), before initiation of study treatment. Background: Early studies indicated that cholesterol levels decrease significantly after ACS. However, most studies were small or did not measure low-density lipoprotein cholesterol (LDL-C) directly, and many used nonfasting or retrospective data. More recent studies suggest less pronounced changes in cholesterol levels after ACS. Methods: The LUNAR trial is a prospective, multicenter, randomized, open-label study in adults hospitalized for acute ST-segment elevation myocardial infarction (STEMI), non-STEMI, or unstable angina (UA). Blood samples were taken at median times after onset of ACS symptoms of 26 h (Day 1, fasting or nonfasting sample), 43 h (Day 2, fasting sample), and 84 h (Day 4, fasting sample) for direct measurement of serum lipid levels before study treatments were started. Results: Of 507 patients available for analysis, 212 were admitted for STEMI, 176 for non-STEMI, and 119 for UA. The LDL-C levels decreased in the 24 h after admission (from 136.2 to 133.5 mg/dl), followed by an increase over the subsequent 2 days (to 141.8 mg/dl). These changes did not seem to be clinically meaningful. Similar changes were observed for total cholesterol and smaller changes for high-density lipoprotein cholesterol; fasting triglyceride levels did not change. Conclusions: Mean lipid levels vary relatively little in the 4 days after an ACS and can be used to guide selection of lipid-lowering medication. (LUNAR Phase IIIb Study Comparing Rosuvastatin and Atorvastatin in Subjects With Acute Coronary Syndromes; NCT00214630) [Copyright &y& Elsevier]

Although angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and β-blockers have been proved to reduce mortality in patients with heart failure post–acute myocardial infarction (AMI), studies show that these agents are consistently underused in this population. Further, morbidity and mortality remain high even when standard-of-care therapies are applied. Thus, new strategies have been sought to better counteract the maladaptive effects of neurohormonal stimulation in post-AMI heart failure. The Eplerenone Post–Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) demonstrated that the selective aldosterone blocker eplerenone, when used in addition to standard therapy, results in significant incremental improvements in survival and morbidity and is safe and well tolerated in this setting. Based on this, major therapeutic guidelines in the United States and Europe now strongly recommend that all eligible patients with concomitant heart failure post-AMI be treated with an aldosterone blocker in addition to an ACE inhibitor (or an ARB) and a β-blocker. To achieve needed improvements in outcomes in this population, early and consistent initiation of these evidence-based, guideline-recommended therapies in all eligible patients is crucial. [Copyright &y& Elsevier]

Objectives: This study sought to assess the impact of the selective aldosterone blocker eplerenone on mortality 30 days after randomization in patients after acute myocardial infarction (AMI) with a left ventricular ejection fraction (LVEF) ≤40% and clinical signs of heart failure. Background: In the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), eplerenone reduced all-cause mortality by 15% (p = 0.008) over a mean follow-up of 16 months when used with standard therapy in patients after AMI with an LVEF ≤40% and clinical signs of heart failure. Methods: We analyzed the effect of eplerenone 25 mg/day initiated 3 to 14 days after AMI (mean, 7.3 days) on the co-primary end points of time to death from any cause and the composite end point of time to death from cardiovascular (CV) causes or hospitalization for CV events, and the secondary end points of CV mortality, sudden cardiac death, and fatal/nonfatal hospitalization for heart failure, after 30 days of therapy in the EPHESUS trial. Results: At 30 days after randomization, eplerenone reduced the risk of all-cause mortality by 31% (3.2% vs. 4.6% in eplerenone and placebo-treated patients, respectively; p = 0.004) and reduced the risk of CV mortality/CV hospitalization by 13% (8.6% vs. 9.9% in eplerenone and placebo-treated patients, respectively; p = 0.074). Eplerenone also reduced the risk of CV mortality by 32% (p = 0.003) and the risk of sudden cardiac death by 37% (p = 0.051). Conclusions: Eplerenone 25 mg/day significantly reduced all-cause mortality 30 days after randomization (when initiated at a mean of 7.3 days after AMI) in addition to conventional therapy in patients with an LVEF ≤40% and signs of heart failure. Based on its early survival benefit, eplerenone should be administered in the hospital after AMI. [Copyright &y& Elsevier]

Heart failure continues to significantly impact morbidity and mortality after acute myocardial infarction (AMI), especially when associated with left ventricular systolic dysfunction (LVSD). Therefore, routine use of optimal therapy for patients with heart failure after AMI is needed in the future. Data from the Eplerenone Post–Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) has demonstrated that addition of eplerenone to standard therapy in patients with LVSD and clinical heart failure post-AMI significantly improves outcomes in these patients, providing the basis for acceptance of aldosterone blockade as an integral component of therapy. However, further studies are needed to more broadly explore the usefulness of aldosterone blockade in heart failure therapy. As research clarifies the many complex pathophysiologic processes involved in post-AMI remodeling, treatment should continue to move beyond symptom-targeted therapies to disease- and mechanism-targeted therapies that will further improve outcomes in the setting of heart failure post-AMI and beyond. [Copyright &y& Elsevier]

Abstract: Objectives: To examine the prevalence of peripheral artery disease (PAD) and the relationship between PAD and cardiovascular (CV) outcomes in subjects with left ventricular systolic dysfunction, heart failure or both after acute myocardial infarction (MI). Background: PAD is associated with poorer prognosis in patients with stable and unstable coronary heart disease but whether PAD is associated with worse outcomes following substantial acute MI is unknown. Methods: Univariate and multivariate Cox proportional hazards modelling was used to compare clinical outcomes in an individual-patient meta-analysis of 4 trials (CAPRICORN, EPHESUS, OPTIMAAL and VALIANT). Results: Of the 28,771 patients randomized, 2357 (8.2%) had PAD. These patients were older and had more co-morbidity and were less likely to be prescribed aspirin or a beta-blocker compared to patients without PAD. Over a mean follow-up of 2.7years, 5121 (17.8%) patients died and 15,055 (52.3%) experienced CV death or hospitalization. PAD was an independent predictor of all individual and composite CV outcomes examined (including heart failure), with the exception of stroke. In patients with PAD (compared to those without PAD), the adjusted hazard ratio (HR) for all-cause mortality was 1.25 (95% CI 1.15–1.37; p<0.001) and the HR for CV death, non-fatal MI, non-fatal stroke or heart failure hospitalization was 1.24 (1.16–1.33; p<0.001). Conclusions: PAD is common and is an independent predictor of worse outcomes in patients already at high risk after MI because of left ventricular systolic dysfunction, heart failure or both. These patients represent an important group for intensive application of secondary preventive therapies. [Copyright &y& Elsevier]

Objectives: We sought to determine whether angiotensin-converting enzyme inhibition (ACE-I) (i.e., quinapril) prevents transient ischemia (exertional and spontaneous) in patients with coronary artery disease (CAD).Background: It is known that ACE-I reduces the risk of death, myocardial infarction (MI), and other CAD-related outcomes in high-risk patients. Numerous studies have confirmed that ACE-I improves coronary flow and endothelial function. Whether ACE-I also decreases transient ischemia is unclear, because no studies have been adequately designed or sufficiently powered to evaluate this issue.Methods: Using a randomized, double-blinded, placebo-controlled, multicenter design, we enrolled 336 CAD patients with stable angina. None had uncontrolled hypertension, left ventricular (LV) dysfunction, or recent MI, and all developed electrocardiographic (ECG) evidence of ischemia during exercise. They were randomly assigned to one of two groups: 40 mg/day quinapril (n = 177) or placebo (n = 159) for 8 weeks. Patients then entered an additional eight-week treatment phase to examine the full dose range. Those assigned to 40 mg quinapril continued that dose and those assigned to placebo were titrated to 80 mg/day. Treadmill testing, the Seattle Angina Questionnaire, and ambulatory ECG monitoring were used to assess responses at baseline and at 8 and 16 weeks.Results: The groups did not differ significantly at entry or in terms of indexes assessing myocardial ischemia at 8 or 16 weeks of treatment. In this low-risk population, ACE-I was not associated with serious adverse events.Conclusions: Our findings suggest short-term ACE-I in CAD patients without hypertension, LV dysfunction, or acute MI is not associated with significant effects on transient ischemia. [Copyright &y& Elsevier]