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Background: Despite the known benefit of intensive statin therapy for reducing future cardiovascular events, its effectiveness in women has been questioned by some.Methods and Results: In the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) trial, 911 (21.9%) women and 3251 (78.1%) men were randomized to intensive statin (atorvastatin 80 mg) versus standard therapy (pravastatin 40 mg) therapy for a median duration of 2.1 years. The primary end point was death, myocardial infarction, unstable angina; revascularization (occurring after 30 days); or stroke. Safety end points included elevations in liver function tests, creatine kinase, and myalgias/myositis. Women had a reduction in low-density lipoprotein (LDL) of 42.8% from baseline at 30 days (to a median of 60 mg/dL) in the intensive therapy arm, with 88.8% reaching the LDL goal of <100 mg/dL and 65.0% of <70 mg/dL, compared with a 16.8% reduction in LDL (to a median of 88 mg/dL) in the standard therapy arm. Women receiving intensive statin therapy had a significant 25% relative reduction over standard dose (hazard ratio, 0.75; 95% CI, 0.57 to 0.99; P=0.04) for the primary composite end point compared with a 14% reduction for men (hazard ratio, 0.86; 95% CI, 0.75 to 0.99; P=0.04; P-interaction, 0.38). No differences were observed between sexes for safety (all P-interaction ≥0.11).Conclusions: This trial provides evidence that both women and men derived benefit from intensive statin therapy after acute coronary syndrome, and thus, sex should not be a factor in determining who should be treated with intensive statin therapy. [ABSTRACT FROM AUTHOR]

Context: High platelet reactivity while receiving clopidogrel has been linked to cardiovascular events after percutaneous coronary intervention (PCI), but a treatment strategy for this issue is not well defined.Objective: To evaluate the effect of high-dose compared with standard-dose clopidogrel in patients with high on-treatment platelet reactivity after PCI.Design, Setting, and Patients: Randomized, double-blind, active-control trial (Gauging Responsiveness with A VerifyNow assay-Impact on Thrombosis And Safety [GRAVITAS]) of 2214 patients with high on-treatment reactivity 12 to 24 hours after PCI with drug-eluting stents at 83 centers in North America between July 2008 and April 2010.Interventions: High-dose clopidogrel (600-mg initial dose, 150 mg daily thereafter) or standard-dose clopidogrel (no additional loading dose, 75 mg daily) for 6 months.Main Outcome Measures: The primary end point was the 6-month incidence of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis. The key safety end point was severe or moderate bleeding according to the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) definition. A key pharmacodynamic end point was the rate of persistently high on-treatment reactivity at 30 days.Results: At 6 months, the primary end point had occurred in 25 of 1109 patients (2.3%) receiving high-dose clopidogrel compared with 25 of 1105 patients (2.3%) receiving standard-dose clopidogrel (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.58-1.76; P = .97). Severe or moderate bleeding was not increased with the high-dose regimen (15 [1.4%] vs 25 [2.3%], HR, 0.59; 95% CI, 0.31-1.11; P = .10). Compared with standard-dose clopidogrel, high-dose clopidogrel provided a 22% (95% CI, 18%-26%) absolute reduction in the rate of high on-treatment reactivity at 30 days (62%; 95% CI, 59%-65% vs 40%; 95% CI, 37%-43%; P < .001).Conclusions: Among patients with high on-treatment reactivity after PCI with drug-eluting stents, the use of high-dose clopidogrel compared with standard-dose clopidogrel did not reduce the incidence of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis.Trial Registration: clinicaltrials.gov Identifier: NCT00645918. [ABSTRACT FROM AUTHOR]

Aims The NCDR ACTION Registry-GWTG collects detailed in-hospital clinical, process-of-care and outcomes data for patients admitted with acute myocardial infarction (AMI) in the USA. The registry is a national AMI surveillance system that contributes to the scientific enquiry process of AMI care through the facilitation of local and national quality improvement efforts. Interventions No treatments are mandated, participating centres receive routine quality-of-care and outcomes performance feedback reports and access to quality of care tools, such as dosing algorithms and standing orders. Population AMI patients are retrospectively identified. No informed consent is required, as data are anonymised. From January 2007 to date, 147 165 records have been submitted from 383 participating US hospitals. Patients with a primary diagnosis of ST-segment elevation myocardial infarction or non-ST-segment elevation myocardial infarction are eligible for enrolment in the registry. These patients must have ischemic symptoms and electrocardiogram changes, and/or positive cardiac markers within 24 hours of initial presentation. Baseline data Approximately 350 fields encompassing patient demographics, medical history and risk factors, hospital presentation, initial cardiac status, medications and associated doses, reperfusion strategy, procedures, laboratory values, and outcomes. Data are manually entered by study personnel; there are non-financial incentives at the hospital level. Completeness within the registry is noteworthy with most fields at less than 5% missing. Endpoints Main outcome measures include American College of Cardiology/American Heart Association myocardial infarction performance indicators, as well as in-hospital patient outcomes. Data are available for research by application to: http://www.ncdr.com. [ABSTRACT FROM AUTHOR]

At the most severe end of the spectrum of acute coronary syndromes is ST-segment elevation myocardial infarction (STEMI), which usually occurs when a fibrin-rich thrombus completely occludes an epicardial coronary artery. The diagnosis of STEMI is based on clinical characteristics and persistent ST-segment elevation as demonstrated by 12-lead electrocardiography. Patients with STEMI should undergo rapid assessment for reperfusion therapy, and a reperfusion strategy should be implemented promptly after the patient's contact with the health care system. Two methods are currently available for establishing timely coronary reperfusion: primary percutaneous coronary intervention and fibrinolytic therapy. Percutaneous coronary intervention is the preferred method but is not always available. Antiplatelet agents and anticoagulants are critical adjuncts to reperfusion. This article summarizes the current evidence-based guidelines for the diagnosis and management of STEMI. This summary is followed by a brief discussion of the role of noninvasive stress testing in the assessment of patients with acute coronary syndrome and their selection for coronary revascularization. [ABSTRACT FROM AUTHOR]

Background: Allograft-prosthetic composite reconstruction of the proximal part of the tibia is one option following resection of a skeletal tumor. Previous studies with use of this technique have found a high prevalence of complications, including fracture, infection, extensor mechanism insufficiency, and loosening. To address some of these problems, we adopted certain measures, including muscle flap coverage, meticulous tendon reconstruction, rigid implant fixation, and careful rehabilitation. The goal of the present study was to evaluate the functional outcome and complications in patients undergoing allograft-prosthetic composite reconstruction of the proximal part of the tibia.Methods: Twelve patients who underwent allograft-prosthetic composite reconstruction of the proximal part of the tibia after tumor resection were retrospectively evaluated at a median follow-up of forty-nine months. Clinical records and radiographs were reviewed to evaluate patient outcome, healing at the allograft-host junction, function, construct survival, and complications.Results: Nine patients had no extensor lag, and three patients had 5 degrees to 15 degrees of extensor lag. The mean amount of knee flexion was 103 degrees (range, 60 degrees to 120 degrees ). The mean Musculoskeletal Tumor Society score was 24.3 (81%) of a maximum of 30. Complete bone union occurred in nine patients, and partial union occurred in three patients. At the time of writing, no secondary bone-grafting procedures had been required to achieve union, and no revision or removal of the reconstruction had been performed. Rotational or free flaps provided satisfactory wound coverage in all patients. A deep infection occurred in one patient whose allograft and prosthesis were successfully retained after treatment with surgical débridement and intravenous antibiotics.Conclusions: After osteoarticular resection of destructive tumors of the proximal part of the tibia, an allograft-prosthetic composite reconstruction can provide consistently good functional results with an acceptably low complication rate. Technical aspects of the procedure that may favorably affect outcome include soft-tissue coverage with muscle flaps and rigid fixation with a long-stemmed implant. [ABSTRACT FROM AUTHOR]

AZD6140, the first reversible oral P2Y12 receptor antagonist, exhibits greater and more consistent inhibition of platelet aggregation than the irreversible thienopyridine clopidogrel. As a result of its reversible effect, AZD6140 may pose less risk for bleeding when antiplatelet treatment cannot be stopped at least 5 days before coronary artery bypass graft (CABG) surgery or other invasive procedures. The Dose conflrmation Study assessing anti-Platelet Effects of AZD6140 vs. clopidogRel in NSTEMI (DISPERSE2) trial showed overall comparable bleeding rates with antiplatelet treatment with AZD6140 90 mg twice daily or 180 mg twice daily vs. clopidogrel 75 mg once daily in 984 patients with non-ST-elevation acute coronary syndromes. A post hoc exploratory analysis of bleeding outcomes in the subset of 84 patients undergoing CABG in DISPERSE2 suggests reduced risk for total bleeding (41% and 58% vs. 62%), all major bleeding (38% and 50% vs. 62%), and life-threatening bleeding (22% and 38% vs. 54%) with AZD6140 90 mg ( n = 32) and 180 mg ( n = 26) vs. clopidogrel ( n = 26) respectively. Trends suggested that major bleeding rates were reduced with AZD6140 (combined groups) vs. clopidogrel when treatment was stopped <= 5 days prior to surgery (39% vs. 63%, p = 0.15) but not when treatment was stopped > 5 days before surgery (50% vs. 60%). This observation is consistent with the reversible binding of AZD6140 to the P2Y12 receptor. Further prospective studies are planned to assess the relationship between this potential clinical benefit of AZD6140 and the reversibility of its antiplatelet effects. [ABSTRACT FROM AUTHOR]

Context: Although an invasive strategy is frequently used in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS), data from some trials suggest that this strategy may not benefit women.Objective: To conduct a meta-analysis of randomized trials to compare the effects of an invasive vs conservative strategy in women and men with NSTE ACS.Data Sources: Trials were identified through a computerized literature search of the MEDLINE and Cochrane databases (1970-April 2008) using the search terms invasive strategy, conservative strategy, selective invasive strategy, acute coronary syndromes, non-ST-elevation myocardial infarction, and unstable angina.Study Selection: Randomized clinical trials comparing an invasive vs conservative treatment strategy in patients with NSTE ACS.Data Extraction: The principal investigators for each trial provided the sex-specific incidences of death, myocardial infarction (MI), and rehospitalization with ACS through 12 months of follow-up.Data Synthesis: Data were combined across 8 trials (3075 women and 7075 men). The odds ratio (OR) for the composite of death, MI, or ACS for invasive vs conservative strategy in women was 0.81 (95% confidence interval [CI], 0.65-1.01; 21.1% vs 25.0%) and in men was 0.73 (95% CI, 0.55-0.98; 21.2% vs 26.3%) without significant heterogeneity between sexes (P for interaction = .26). Among biomarker-positive women, an invasive strategy was associated with a 33% lower odds of death, MI, or ACS (OR, 0.67; 95% CI, 0.50-0.88) and a nonsignificant 23% lower odds of death or MI (OR, 0.77; 95% CI, 0.47-1.25). In contrast, an invasive strategy was not associated with a significant reduction in the triple composite end point in biomarker-negative women (OR, 0.94; 95% CI, 0.61-1.44; P for interaction = .36) and was associated with a nonsignificant 35% higher odds of death or MI (OR, 1.35; 95% CI, 0.78-2.35; P for interaction = .08). Among men, the OR for death, MI, or ACS was 0.56 (95% CI, 0.46-0.67) if biomarker-positive and 0.72 (95% CI, 0.51-1.01) if biomarker-negative (P for interaction = .09).Conclusions: In NSTE ACS, an invasive strategy has a comparable benefit in men and high-risk women for reducing the composite end point of death, MI, or rehospitalization with ACS. In contrast, our data provide evidence supporting the new guideline recommendation for a conservative strategy in low-risk women. [ABSTRACT FROM AUTHOR]

Context: Abdominal obesity is associated with metabolic abnormalities and increased risk of atherosclerotic cardiovascular disease. However, no obesity management strategy has demonstrated the ability to slow progression of coronary disease.Objective: To determine whether weight loss and metabolic effects of the selective cannabinoid type 1 receptor antagonist rimonabant reduces progression of coronary disease in patients with abdominal obesity and the metabolic syndrome.Design, Setting, and Patients: Randomized, double-blinded, placebo-controlled, 2-group, parallel-group trial (enrollment December 2004-December 2005) comparing rimonabant with placebo in 839 patients at 112 centers in North America, Europe, and Australia.Interventions: Patients received dietary counseling, were randomized to receive rimonabant (20 mg daily) or matching placebo, and underwent coronary intravascular ultrasonography at baseline (n = 839) and study completion (n = 676).Main Outcome Measures: The primary efficacy parameter was change in percent atheroma volume (PAV); the secondary efficacy parameter was change in normalized total atheroma volume (TAV).Results: In the rimonabant vs placebo groups, PAV (95% confidence interval [CI]) increased 0.25% (-0.04% to 0.54%) vs 0.51% (0.22% to 0.80%) (P = .22), respectively, and TAV decreased 2.2 mm3 (-4.09 to -0.24) vs an increase of 0.88 mm3 (-1.03 to 2.79) (P = .03). In the rimonabant vs placebo groups, imputing results based on baseline characteristics for patients not completing the trial, PAV increased 0.25% (-0.04% to 0.55%) vs 0.57% (0.29% to 0.84%) (P = .13), and TAV decreased 1.95 mm3 (-3.8 to -0.10) vs an increase of 1.19 mm3 (-0.73 to 3.12) (P = .02). Rimonabant-treated patients had a larger reduction in body weight (4.3 kg [-5.1 to -3.5] vs 0.5 kg [-1.3 to 0.3]) and greater decrease in waist circumference (4.5 cm [-5.4 to -3.7] vs 1.0 cm [-1.9 to -0.2]) (P < .001 for both comparisons). In the rimonabant vs placebo groups, high-density lipoprotein cholesterol levels increased 5.8 mg/dL (4.9 to 6.8) (22.4%) vs 1.8 mg/dL (0.9 to 2.7) (6.9%) (P < .001), and median triglyceride levels decreased 24.8 mg/dL (-35.4 to -17.3) (20.5%) vs 8.9 mg/dL (-14.2 to -1.8) (6.2%) (P < .001). Rimonabant-treated patients had greater decreases in high-sensitivity C-reactive protein (1.3 mg/dL [-1.7 to -1.2] [50.3%] vs 0.9 mg/dL [-1.4 to -0.5] [30.9%]) and less increase in glycated hemoglobin levels (0.11% [0.02% to 0.20%] vs 0.40% [0.31% to 0.49%]) (P < .001 for both comparisons). Psychiatric adverse effects were more common in the rimonabant group (43.4% vs 28.4%, P < .001).Conclusions: After 18 months of treatment, the study failed to show an effect for rimonabant on disease progression for the primary end point (PAV) but showed a favorable effect on the secondary end point (TAV). Determining whether rimonabant is useful in management of coronary disease will require additional imaging and outcomes trials, which are currently under way.Trial Registration: clinicaltrials.gov Identifier: NCT00124332. [ABSTRACT FROM AUTHOR]

Obese patients are at increased risk for developing numerous cardiometabolic complications, including hypertension, insulin resistance, diabetes mellitus, dyslipidemia, and cardiovascular disease (CVD). These complications are associated with an increase in mortality and appear to be related to the changes in adipocytcs that occur with obesity. The enlarged adipocytes found in obese individuals release more glycerol, free fatty acids, and proinflammatory factors and less adiponectin. Some of these changes result in insulin resistance, which appears to be integral to the development of the obesity-associated cardiometabolic complications. Weight loss and increased physical activity are key to reducing the risk for obese individuals to develop cardiovascular complications. However, many patients also require drug therapy. Because many obese patients have multiple cardiometabolic complications, ideally, drug therapy that has positive effects on multiple CVD risk factors should be used. Therapies directed at obesity, such as sibutramine and endocannabinoid receptor blockers (eg, rimonabant), have shown improvements in weight, blood pressure, the lipid profile, and glucose levels. [ABSTRACT FROM AUTHOR]