Optimal medical therapy with or without percutaneous coronary intervention in women with stable coronary disease: A pre-specified subset analysis of the Clinical Outcomes Utilizing Revascularization and Aggressive druG Evaluation (COURAGE) trial.

OBJECTIVES: To determine whether sex-based differences exist in clinical effectiveness of percutaneous coronary intervention (PCI) when added to optimal medical therapy (OMT) in patients with stable coronary artery disease. BACKGROUND: A prior pre-specified unadjusted analysis from COURAGE showed that women randomized to PCI had a lower rate of death or myocardial infarction during a median 4.6-year follow-up with a trend for interaction with respect to sex. METHODS: We analyzed outcomes in 338 women (15%) and 1949 men (85%) randomized to PCI plus OMT versus OMT alone after adjustment for relevant baseline characteristics. RESULTS: There was no difference in treatment effect by sex for the primary end point (death or myocardial infarction; HR, 0.89; 95% CI, 0.77-1.03 for women and HR, 1.02, 95% CI 0.96-1.10 for men; P for interaction = .07). Although the event rate was low, a trend for interaction by sex was nonetheless noted for hospitalization for heart failure, with only women, but not men, assigned to PCI experiencing significantly fewer events as compared to their counterparts receiving OMT alone (HR, 0.59; 95% CI, 0.40-0.84, P < .001 for women and HR, 0.86; 95% CI, 0.74-1.01, P = .47 for men; P for interaction = .02). Both sexes randomized to PCI experienced significantly reduced need for subsequent revascularization (HR, 0.72; 95% CI, 0.62-0.83, P < .001 for women; HR, 0.84; 95% CI, 0.79-0.89, P < .001 for men; P for interaction = .02) with evidence of a sex-based differential treatment effect. CONCLUSION: In this adjusted analysis of the COURAGE trial, there were no significant differences in treatment effect on major outcomes between men and women. However, women assigned to PCI demonstrated a greater benefit as compared to men, with a reduction in heart failure hospitalization and need for future revascularization. These exploratory observations require further prospective study.

Effect of soy nuts and equol status on blood pressure, lipids and inflammation in postmenopausal women stratified by metabolic syndrome status.

OBJECTIVE: Soy has been associated with lower risk of cardiovascular disease in Asian countries which consume daily soy. Our study examined whether production of equol, an estrogen metabolite, affected the ability of soy nuts to improve cardiovascular risk factors. MATERIALS/METHODS: Sixty postmenopausal women participated in a randomized, controlled, crossover trial of a Therapeutic Lifestyle Changes (TLC) diet alone and a TLC diet in which 0.5 cup of soy nuts (25 g of soy protein and 101 mg of aglycone isoflavones) replaced 25 g of nonsoy protein daily. Each diet was followed for 8 weeks at the end of which blood pressure (BP), lipid levels, adhesion molecules and inflammatory markers were measured. RESULTS: Women with MetS had significantly higher baseline body mass index (BMI), BP, triglycerides (TG), and soluble intercellular adhesion molecule (sICAM) than women without MetS. In women with MetS on the soy diet, significant reductions in diastolic BP (7.7%; P=0.02), TG (22.9%; P=0.02), C-reactive protein (CRP) (21.4%; P=0.01) and sICAM (7.3%; P=0.03) were noted among equol producers compared to levels on the TLC diet. No significant changes were noted in equol nonproducers. Similarly, in women without MetS, only equol producers had significant reductions in diastolic BP (3.3%, P=0.02) and CRP (30%, P=0.04). In contrast to women with MetS, TG and sICAM levels were not affected in women without MetS, a finding possibly related to lower baseline levels. CONCLUSIONS: Cardiovascular risk reduction with soy nuts is not uniform and may be greater among producers of equol.

Update on ranolazine in the management of angina.

Mortality rates attributable to coronary heart disease have declined in recent years, possibly related to changes in clinical presentation patterns and use of proven secondary prevention strategies. Chronic stable angina (CSA) remains prevalent, and the goal of treatment is control of symptoms and reduction in cardiovascular events. Ranolazine is a selective inhibitor of the late sodium current in myocytes with anti-ischemic and metabolic properties. It was approved by the US Food and Drug Administration in 2006 for use in patients with CSA. Multiple, randomized, placebo-controlled trials have shown that ranolazine improves functional capacity and decreases anginal episodes in CSA patients, despite a lack of a significant hemodynamic effect. Ranolazine did not improve cardiovascular mortality or affect incidence of myocardial infarction in the MERLIN (Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndrome)-TIMI (Thrombolysis In Myocardial Infarction) 36 trial, but significantly decreased the incidence of recurrent angina. More recently, ranolazine has been shown to have beneficial and potent antiarrhythmic effects, both on supraventricular and ventricular tachyarrhythmias, largely due to its inhibition of the late sodium current. Randomized controlled trials testing these effects are underway. Lastly, ranolazine appears to be cost-effective due to its ability to decrease angina-related hospitalizations and improve quality of life.

Low levels of high-density lipoprotein cholesterol and increased risk of cardiovascular events in stable ischemic heart disease patients: A post-hoc analysis from the COURAGE Trial (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation).

OBJECTIVES: This study sought to assess the independent effect of high-density lipoprotein-cholesterol (HDL-C) level on cardiovascular risk in patients with stable ischemic heart disease (SIHD) who were receiving optimal medical therapy (OMT). BACKGROUND: Although low HDL-C level is a powerful and independent predictor of cardiovascular risk, recent data suggest that this may not apply when low-density lipoprotein-cholesterol (LDL-C) is reduced to optimal levels using intensive statin therapy. METHODS: We performed a post-hoc analysis in 2,193 men and women with SIHD from the COURAGE trial. The primary outcome measure was the composite of death from any cause or nonfatal myocardial infarction (MI). The independent association between HDL-C levels measured after 6 months on OMT and the rate of cardiovascular events after 4 years was assessed. Similar analyses were performed separately in subjects with LDL-C levels below 70 mg/dl (1.8 mmol/l). RESULTS: In the overall population, the rate of death/MI was 33% lower in the highest HDL-C quartile as compared with the lowest quartile, with quartile of HDL-C being a significant, independent predictor of death/MI (p = 0.05), but with no interaction for LDL-C category (p = 0.40). Among subjects with LDL-C levels <70 mg/dl, those in the highest quintile of HDL-C had a 65% relative risk reduction in death or MI as compared with the lowest quintile, with HDL-C quintile demonstrating a significant, inverse predictive effect (p = 0.02). CONCLUSIONS: In this post-hoc analysis, patients with SIHD continued to experience incremental cardiovascular risk associated with low HDL-C levels despite OMT during long-term follow-up. This relationship persisted and appeared more prominent even when LDL-C was reduced to optimal levels with intensive dyslipidemic therapy. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; NCT00007657).

Relation of admission high-density lipoprotein cholesterol level and in-hospital mortality in patients with acute non-ST segment elevation myocardial infarction (from the National Cardiovascular Data Registry).

Despite recent therapeutic advances, significant residual risk for in-hospital mortality persists among patients admitted with acute myocardial infarction (MI). Low levels of high-density lipoprotein cholesterol (HDL-C), a known independent predictor of increased cardiovascular events, may be an important modulator of heightened risk after acute MI. We evaluated admission HDL-C levels among 98,276 patients with non-ST elevation myocardial infarction with acute MI from the Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With the Guidelines (ACTION Registry-GWTG) program who were enrolled from 490 United States hospitals from January 2007 to December 2010. Clinical characteristics, treatments, atherosclerotic burden, and in-hospital outcomes were analyzed by quartiles of admission HDL-C (Q1: 10 to 30 mg/dl; Q2: 30.1 to 36.9 mg/dl; Q3: 37 to 45 mg/dl; and Q4: 45.1 to 100 mg/dl). Logistic regression was used to explore the relation among HDL-C quartiles, coronary artery disease severity, and in-hospital mortality. Almost half of the patients with acute MI had low admission levels of HDL-C (less than the median 36.9 mg/dl). Such patients were younger, more often men, white, obese, diabetic, smokers, and had higher rates of previous cardiovascular events. After multivariate adjustment, patients with low HDL-C levels had greater extent of severe angiographic multivessel coronary narrowings and higher mortality. Among the 26% of patients in the lowest HDL-C quartile (≤30 mg/dl), there was a 16% greater risk of in-hospital mortality compared with patients in the highest HDL-C quartile (p = 0.012). In conclusion, low levels of HDL-C were common in patients admitted with acute MI and were associated with more extensive angiographic coronary disease. Very low levels of admission HDL-C were observed in one-quarter of patients and associated with significantly higher in-hospital mortality.

Dabigatran: a new option for anticoagulation in atrial fibrillation and venous thromboembolism.

For several decades now, oral anticoagulation with warfarin has represented the cornerstone of measures to prevent occurrence of ischemic stroke in high-risk patients with atrial fibrillation. However, the mechanism of action and pharmacokinetic profile of this vitamin K antagonist confers a narrow therapeutic range and makes it prone to drug and dietary interactions, requiring frequent monitoring of its effectiveness. The recently introduced oral direct thrombin antagonist, dabigatran, has been shown in phase III clinical trials to be noninferior in efficacy to warfarin for the prevention of thromboembolic events in patients with atrial fibrillation, as well as in treatment of acute venous thromboembolism. In this article, we review the factors necessitating the development of dabigatran, summarize key clinical trial evidence leading to its approval, and discuss its potential role as an alternative to warfarin in current clinical practice.

Duration of dual antiplatelet therapy following percutaneous coronary intervention with drug-eluting stents: a review of recent evidence.

The introduction of drug-eluting stents represented a significant advancement in interventional cardiology, offering a solution to the long-standing problem of restenosis after coronary revascularization. At present, drug-eluting stents are being used in a majority of stent procedures. However, they are mechanistically prone to develop late stent thrombosis and require prolonged therapy with aspirin and a thienopyridine to prevent this complication. Adequate evidence regarding the optimal duration of dual antiplatelet therapy is lacking, and the initial guidelines on this issue were framed empirically in the absence of robust data from clinical trials and analyses. In this article, we briefly review the evolution of dual antiplatelet therapy and discuss the findings from some recent analyses that test both the efficacy as well as the safety of extended and intensive platelet inhibition with aspirin and thienopyridines.

Office-based global cardiometabolic risk assessment: a simple tool incorporating nontraditional markers.

To facilitate comprehensive cardiometabolic risk assessment, we developed a simple 12-point checklist of traditional and emerging risk factors. We recently analyzed data from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI 22) trial of 4162 high-risk patients hospitalized with recent acute coronary syndrome, and found that an increasing cardiometabolic risk factor count was associated with increasing risk of cardiovascular events over the next 2 years. In addition, we observed that the average number of risk factors a given patient had was 5, with some risk factors like obesity having clustering of additional risk factors, suggesting the need to assess the full list of risk factors to be able to provide comprehensive risk factor assessment and modification. We now have developed a 1-page patient encounter sheet to facilitate rapid assessment of these 12 cardiometabolic risk factors in a busy clinical office setting. It is hoped that with the simple risk assessment tool provided, clinicians would be able to comprehensively screen for and treat these traditional and nontraditional risk markers. As such, this could motivate both patients and physicians to work jointly toward reducing global cardiometabolic risk.

Distribution of traditional and novel risk factors and their relation to subsequent cardiovascular events in patients with acute coronary syndromes (from the PROVE IT-TIMI 22 trial).

Current guidelines recommend risk stratification largely based on traditional risk factors such as those in the Framingham Risk Score. We studied the distribution of 12 traditional and non-traditional risk markers (age > or =65 years, male gender, family history of premature coronary heart disease, low-density lipoprotein cholesterol > or =70 mg/dl, high-density lipoprotein cholesterol <40 mg/dl in men and <50 mg/dl in women, systolic blood pressure >130 mm Hg, diabetes mellitus, smoking, C-reactive protein > or =2 mg/L, triglycerides >150 mg/dl, prediabetes defined as a fasting glucose level 100 to 125 mg/dl or hemoglobin A1c >6, and obesity defined as body mass index > or =30 kg/m(2)) in 3,675 patients from the PROVE IT-TIMI 22 trial at 4 months and evaluated the risk of cardiovascular events stratified by the number of risk factors. The median number of risk factors was 5. In individual risk factor subgroups, men, smokers, hypertensives, and patients with increased low-density lipoprotein cholesterol had just that added risk factor compared to their counterparts (median 5 vs 4). In contrast, patients with diabetes, prediabetes, and increased triglycerides, C-reactive protein, or body mass index had not only that, but also another added risk factor (median 6 vs 4). A higher risk factor count was strongly related with increased rate of death, myocardial infarction, unstable angina, stroke, or revascularization, from 0% to 38.6% at 2 years for 0 to > or =9 risk factors (p <0.0001). In conclusion, with the observed "clustering" of risk factors and the link between increasing risk factor count and adverse outcomes in a patient with 1 diagnosed risk factor, a comprehensive review of traditional and novel risk factors is important to fully assess cardiovascular risk.

Complete resolution of a mitral valve vegetation with anticoagulation in seronegative antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is a disorder characterized by recurrent venous or arterial thrombosis and/or fetal loss; involvement of cardiac valves is also seen. A seronegative variant has been described previously. We report a case of a woman with recurrent pregnancy loss, prior strokes, and a negative workup for known antiphospholipid antibodies. During her current pregnancy, she presented with acute stroke and mitral valve vegetation. Her workup for antiphospholipid syndrome and other thrombophilias remained negative even after the stroke. Her mitral valve vegetation resolved completely with aspirin, heparin, and warfarin. We believe this to be the first report of complete resolution of valvular vegetation with antiplatelet and anticoagulant therapy alone in a patient with seronegative antiphospholipid syndrome. Moreover, this appears to be the first report of stroke associated with this condition.

Atorvastatin and cardiovascular risk in the elderly--patient considerations.

Elderly individuals are at increased risk of coronary heart disease (CHD) and account for a majority of CHD deaths. Several clinical trials have assessed the beneficial effects of statins in individuals with, or at risk of developing, CHD. These trials provide evidence that statins reduce risk and improve clinical outcomes even in older patients; however, statin therapy remains under-utilized among the aged. Atorvastatin has been widely investigated among the older subjects and has the greatest magnitude of favorable effects on clinical outcomes of CHD. The pharmacokinetic properties of atorvastatin allow it to be used every other day, a factor which may decrease adverse events and be especially important in the elderly. The purpose of this article is to review the evidence available from randomized clinical trials regarding the safety and efficacy of atorvastatin in primary and secondary prevention of CHD and stroke in older patients and to discuss issues such as drug interactions, patient compliance and cost-effectiveness, which affect prescription of lipid-lowering therapy among older patients.