Heart Centers for Women: Historical Perspective on Formation and Future Strategies to Reduce Cardiovascular Disease.

Heart Centers for Women (HCW) developed as a response to the need for improved outcomes for women with cardiovascular disease (CVD). From 1984 until 2012, more women died of CVD every single year in comparison with men. Initially, there was limited awareness and sex-specific research regarding mortality or outcomes in women. HCW played an active role in addressing these disparities, provided focused care for women, and contributed to improvements in these gaps. In 2014 and 2015, death from CVD in women had declined below the level of death from CVD in comparison with men. Even though awareness of CVD in women has increased among the public and healthcare providers and both sex- and gender-specific research is currently required in all research trials, not all women have benefitted equally in mortality reduction. New strategies for HCW need to be developed to address these disparities and expand the current HCW model. The HCW care team needs to direct academic curricula on sex- and gender-specific research and care; expand to include other healthcare professionals and other subspecialties; provide new care models; address diversity; and include more male providers.

Safety and Tolerability of CSL112, a Reconstituted, Infusible, Plasma-Derived Apolipoprotein A-I, After Acute Myocardial Infarction: The AEGIS-I Trial (ApoA-I Event Reducing in Ischemic Syndromes I).

BACKGROUND: Human or recombinant apolipoprotein A-I (apoA-I) has been shown to increase high-density lipoprotein-mediated cholesterol efflux capacity and to regress atherosclerotic disease in animal and clinical studies. CSL112 is an infusible, plasma-derived apoA-I that has been studied in normal subjects or those with stable coronary artery disease. This study aimed to characterize the safety, tolerability, pharmacokinetics, and pharmacodynamics of CSL112 in patients with a recent acute myocardial infarction. METHODS: The AEGIS-I trial (Apo-I Event Reducing in Ischemic Syndromes I) was a multicenter, randomized, double-blind, placebo-controlled, dose-ranging phase 2b trial. Patients with myocardial infarction were stratified by renal function and randomized 1:1:1 to CSL112 (2 g apoA-I per dose) and high-dose CSL112 (6 g apoA-I per dose), or placebo for 4 consecutive weekly infusions. Coprimary safety end points were occurrence of either a hepatic safety event (an increase in alanine transaminase >3 times the upper limit of normal or an increase in total bilirubin >2 times the upper limit of normal) or a renal safety event (an increase in serum creatinine >1.5 times the baseline value or a new requirement for renal replacement therapy). RESULTS: A total of 1258 patients were randomized, and 91.2% received all 4 infusions. The difference in incidence rates for an increase in alanine transaminase or total bilirubin between both CSL112 arms and placebo was within the protocol-defined noninferiority margin of 4%. Similarly, the difference in incidence rates for an increase in serum creatinine or a new requirement for renal replacement therapy was within the protocol-defined noninferiority margin of 5%. CSL112 was associated with increases in apoA-I and ex vivo cholesterol efflux similar to that achieved in patients with stable coronary artery disease. In regard to the secondary efficacy end point, the risk for the composite of major adverse cardiovascular events among the groups was similar. CONCLUSIONS: Among patients with acute myocardial infarction, 4 weekly infusions of CSL112 are feasible, well tolerated, and not associated with any significant alterations in liver or kidney function or other safety concern. The ability of CSL112 to acutely enhance cholesterol efflux was confirmed. The potential benefit of CSL112 to reduce major adverse cardiovascular events needs to be assessed in an adequately powered phase 3 trial. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT02108262.

The future of cardiovascular clinical research in North America and beyond-addressing challenges and leveraging opportunities through unique academic and grassroots collaborations.

Recent developments have highlighted the challenges facing cardiovascular clinical research in global contemporary practice, particularly in North America, including shifting priorities for drug development targets, increasing regulatory requirements, and expensive operational approaches for conducting randomized clinical trials. Nonetheless, emerging trends such as the consolidation of practices and hospitals into integrated health systems, the integration of electronic health records from thousands of practices into large data repositories to support prospective research studies, and streamlined operational approaches such as registry-based trials and risk-based monitoring have created numerous opportunities to disrupt the clinical research paradigm. Within this context, academic research organizations around the globe, particularly a strengthened collaboration of 3 established academic research organizations in North America, are uniquely positioned to promote and develop grassroots collaborations across all types of clinical practices, to delineate successful solutions to obstacles that limit clinical research initiatives, and to guide the future of cardiovascular research in the global research environment.

The primary and secondary prevention of coronary artery disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).

The following chapter devoted to antithrombotic therapy for chronic coronary artery disease (CAD) is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do or do not outweigh risks, burden, and costs. Grade 2 suggests that individual patient values may lead to different choices (for a full understanding of the grading see the "Grades of Recommendation" chapter by Guyatt et al in this supplement, CHEST 2008; 133[suppl]:123S-131S). Among the key recommendations in this chapter are the following: for patients with non-ST-segment elevation (NSTE)-acute coronary syndrome (ACS) we recommend daily oral aspirin (75-100 mg) [Grade 1A]. For patients with an aspirin allergy, we recommend clopidogrel, 75 mg/d (Grade 1A). For patients who have received clopidogrel and are scheduled for coronary bypass surgery, we suggest discontinuing clopidogrel for 5 days prior to the scheduled surgery (Grade 2A). For patients after myocardial infarction, after ACS, and those with stable CAD and patients after percutaneous coronary intervention (PCI), we recommend daily aspirin (75-100 mg) as indefinite therapy (Grade 1A). We recommend clopidogrel in combination with aspirin for patients experiencing ST-segment elevation (STE) and NSTE-ACS (Grade 1A). For patients with contraindications to aspirin, we recommend clopidogrel as monotherapy (Grade 1A). For long-term treatment after PCI in patients who receive antithrombotic agents such as clopidogrel or warfarin, we recommend aspirin (75 to 100 mg/d) [Grade 1B]. For patients who undergo bare metal stent placement, we recommend the combination of aspirin and clopidogrel for at least 4 weeks (Grade 1A). We recommend that patients receiving drug-eluting stents (DES) receive aspirin (325 mg/d for 3 months followed by 75-100 mg/d) and clopidogrel 75 mg/d for a minimum of 12 months (Grade 2B). For primary prevention in patients with moderate risk for a coronary event, we recommend aspirin, 75-100 mg/d, over either no antithrombotic therapy or vitamin K antagonist (Grade 1A).

Combining enoxaparin and glycoprotein IIb/IIIa antagonists for the treatment of acute coronary syndromes: final results of the National Investigators Collaborating on Enoxaparin-3 (NICE-3) study.

BACKGROUND: In high-risk patients with acute coronary syndromes (ACS), there have been concerns relating to the safety of using low molecular weight heparins (LMWH) in combination with a glycoprotein (GP) IIb/IIIa antagonist, and the continued use of LMWH in patients brought to the cardiac catheterization laboratory for percutaneous coronary intervention (PCI). METHODS: The National Investigators Collaborating on Enoxaparin-3 (NICE-3) study was an open-label observational study of enoxaparin in combination with any 1 of 3 available GP IIb/IIIa antagonists in patients presenting with non-ST-elevation ACS. The primary end point was the incidence of major bleeding not related to coronary artery bypass graft (CABG) surgery. Data were also recorded on the incidence of death, myocardial infarction (MI), and urgent revascularization for repeat ischemia. RESULTS: A total of 671 patients with validated data were treated with enoxaparin; 628 of these patients also received a GP IIb/IIIa antagonist (tirofiban, n = 229; eptifibatide, n = 272; abciximab, n = 127); 283 of 628 underwent percutaneous coronary intervention (PCI). The 30-day incidence of non-CABG major bleeding was 1.9%, and was not significantly higher than a prespecified historical control rate of 2.0%. Outcome events included death (1.0% at hospital discharge and 1.6% at 30 days), MI (3.5% and 5.1%, respectively), and urgent revascularization (2.7% and 6.8%, respectively). CONCLUSIONS: The safety of enoxaparin plus a GP IIb/IIIa antagonist was comparable to that of unfractionated heparin plus a GP IIb/IIIa antagonist, as reported in other recent major trials. Patients undergoing PCI can be safely managed with enoxaparin and a GP IIb/IIIa antagonist, without supplemental use of unfractionated heparin.

Troponin T and quantitative ST-segment depression offer complementary prognostic information in the risk stratification of acute coronary syndrome patients.

OBJECTIVES: Our primary objective was to examine the prognostic relationship between baseline quantitative ST-segment depression (ST) and cardiac troponin T (cTnT) elevation. The secondary objectives were to: 1) examine whether ST provided additional insight into therapeutic efficacy of glycoprotein IIb/IIIa therapy similar to that demonstrated by cTnT; and 2) explore whether the time to evaluation impacted on each marker's relative prognostic utility. BACKGROUND: The relationship between the baseline electrocardiogram (ECG) and cTnT measurements in risk-stratifying patients presenting with acute coronary syndromes (ACS) has not been evaluated comprehensively. METHODS: The study population consisted of 959 patients enrolled in the cTnT substudy of the Platelet IIb/IIIa Antagonism for the Reduction of Acute coronary syndrome events in a Global Organization Network (PARAGON)-B trial. Patients were classified as having no ST (n = 387), 1 mm ST (n = 433), and ST > or =2 mm (n = 139). Forty-percent (n = 381) were classified as cTnT-positive based on a definition of > or =0.1 ng/ml. RESULTS: Six-month death/(re)myocardial infarction rates were 8.4% among cTnT-negative patients with no ST and 26.8% among cTnT-positive patients with ST > or =2 mm. On ECGs done after 6 h of symptom onset, ST > or =2 mm was associated with higher risk compared to its presence on ECGs done earlier (odds ratio [OR] 7.3 vs. 2.1). In contrast, the presence of elevated cTnT within 6 h of symptom was associated with a higher risk of adverse events compared with elevations after 6 h (OR 2.4 vs. 1.5). CONCLUSIONS: Quantitative ST and cTnT status are complementary in assessing risk among ACS patients and both should be employed to determine prognosis and assist in medical decision making.