Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity (SELECT) rationale and design.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality. Although it has been widely appreciated that obesity is a major risk factor for CVD, treatments that produce effective, durable weight loss and the impact of weight reduction in reducing cardiovascular risk have been elusive. Instead, progress in CVD risk reduction has been achieved through medications indicated for controlling lipids, hyperglycemia, blood pressure, heart failure, inflammation, and/or thrombosis. Obesity has been implicated as promoting all these issues, suggesting that sustained, effective weight loss may have independent cardiovascular benefit. GLP-1 receptor agonists (RAs) reduce weight, improve glycemia, decrease cardiovascular events in those with diabetes, and may have additional cardioprotective effects. The GLP-1 RA semaglutide is in phase 3 studies as a medication for obesity treatment at a dose of 2.4 mg subcutaneously (s.c.) once weekly. Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) is a randomized, double-blind, parallel-group trial testing if semaglutide 2.4 mg subcutaneously once weekly is superior to placebo when added to standard of care for preventing major adverse cardiovascular events in patients with established CVD and overweight or obesity but without diabetes. SELECT is the first cardiovascular outcomes trial to evaluate superiority in major adverse cardiovascular events reduction for an antiobesity medication in such a population. As such, SELECT has the potential for advancing new approaches to CVD risk reduction while targeting obesity.

Baseline characteristics of patients enrolled in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL).

BACKGROUND: EXSCEL is a randomized, double-blind, placebo-controlled trial examining the effect of exenatide once-weekly (EQW) versus placebo on time to the primary composite outcome (cardiovascular death, nonfatal myocardial infarction or nonfatal stroke) in patients with type 2 diabetes mellitus (DM) and a wide range of cardiovascular (CV) risk. METHODS: Patients were enrolled at 688 sites in 35 countries. We describe their baseline characteristics according to prior CV event status and compare patients with those enrolled in prior glucagon-like peptide-1 receptor agonist (GLP-1RA) outcomes trials. RESULTS: Of a total of 14,752 participants randomized between June 2010 and September 2015, 6,788 (46.0%) patients were enrolled in Europe; 3,708 (25.1%), North America; 2,727 (18.5%), Latin America; and 1,529 (10.4%), Asia Pacific. Overall, 73% had at least one prior CV event (70% coronary artery disease, 24% peripheral arterial disease, 22% cerebrovascular disease). The median (IQR) age was 63 years (56, 69), 38% were female, median baseline HbA1c was 8.0% (7.3, 8.9) and 16% had a prior history of heart failure. Those without a prior CV event were younger with a shorter duration of diabetes and better renal function than those with at least one prior CV event. Compared with prior GLP-1RA trials, EXSCEL has a larger percentage of patients without a prior CV event and a notable percentage who were taking a dipeptidyl peptidase-4 inhibitor at baseline (15%). CONCLUSIONS: EXSCEL is one of the largest global GLP-1RA trials, evaluating the safety and efficacy of EQW with a broad patient population that may extend generalizability compared to prior GLP-1RA trials (ClinicalTrials.gov number, NCT01144338).

Coronary plaque dimensions and composition by intravascular ultrasound radio frequency lesion segment analysis in stable and unstable angina patients.

AIMS: We hypothesized that the plaque composition and plaque type classification differs between acute coronary syndrome (ACS) and stable angina (SA) patients. METHODS AND RESULTS: We analyzed culprit lesion (CL) and nonculprit lesion (NCL) of ACS patients compared with target lesion (TL) and nontarget lesion (NTL) of SA patients by intravascular ultrasound radio frequency analysis in 874 lesion segments of 424 patients (ACS: 193 patients/SA: 231 patients). Comparing all lesion segments in ACS and SA patients did not show significant differences in absolute or relative plaque composition. However, necrotic core area was larger in CL versus TL (0.9+/-0.7 vs. 0.7+/-0.5 mm, P=0.005) and all plaque components were significantly higher in CL compared with NCL and TL compared with NTL, respectively. A higher amount of thin cap fibroatheroma lesions (15.2 vs. 5.1%, P<0.0001) was detected in ACS compared with SA patients. Fibrocalcific lesions were lower in ACS patients (3 vs. 10.5%, P<0.0001). CONCLUSION: The differentiation in CL/NCL of ACS and TL/NTL of SA patients revealed significant differences in plaque composition and plaque types when examined by intravascular ultrasound radiofrequency analysis. However, considerable overlap between plaque characteristics exists for ACS and SA patients.

Risk of restenosis and health status outcomes for patients undergoing percutaneous coronary intervention versus coronary artery bypass graft surgery.

BACKGROUND: Previous comparisons of percutaneous coronary interventions (PCIs) and coronary artery bypass graft (CABG) surgery have demonstrated similar survival but have also generally found better health status outcomes (symptoms, function, and quality of life) with CABG. The principal limitation of PCI has been the occurrence of restenosis. No previous studies comparing the health status outcomes of PCI and CABG have examined differences in these outcomes as a function of patients' preprocedural risk for restenosis. METHODS AND RESULTS: We examined the health status outcomes, using the Seattle Angina Questionnaire (SAQ), among 1459 consecutive patients (1027 treated with PCI and 432, with CABG), stratified by their risk for restenosis. In multivariable-adjusted, linear regression analyses, no differences in 1-year angina or quality of life were observed among the 37.4% of patients at low risk for restenosis. However, among the 46.7% at intermediate risk for restenosis, 1-year health status scores were moderately better after CABG surgery compared with PCI (difference in SAQ angina frequency scores favoring CABG=6.1+/-1.7 points, P=0.0003; difference in SAQ quality of life=5.8+/-1.6 points, P=0.0004). Even larger differences in 1-year outcomes favoring CABG surgery were observed in patients at high risk for restenosis (SAQ angina frequency difference=10.8+/-4.2, P=0.01; SAQ quality of life difference=10.8+/-3.9, P=0.006). CONCLUSIONS: The relative health status benefits of CABG surgery compared with PCI increase as the risk of restenosis increases. Although selecting CABG or PCI is complex, preprocedural restenosis risk should be considered. It should also be tested as a means for considering drug-eluting as opposed to bare metal stents in PCI.