Background: Glucagon-like peptide 1 agonists differ in chemical structure, duration of action and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. Methods: We randomly assigned patients with type 2 diabetes and cardiovascular disease to the addition of once-weekly subcutaneous injection of albiglutide (30 mg to 50 mg) or matching placebo to standard care. We hypothesized that albiglutide would be noninferior to placebo for the primary outcome of first occurrence of cardiovascular death, myocardial infarction, or stroke. If noninferiority was confirmed by an upper limit of the 95% confidence interval for the hazard ratio of less than 1.30, closed-testing for superiority was prespecified. Findings: Overall, 9463 participants were followed for a median of 1.6 years. The primary composite outcome occurred in 338 of 4731 patients (7.1%; 4.6 events per 100 person-years) in the albiglutide group and in 428 of 4732 patients (9.0%; 5.9 events per 100 person-years) in the placebo group (hazard ratio, 0.78; 95% confidence interval [CI ], 0.68 to 0.90), indicating that albiglutide, was superior to placebo (P<0.0001 for noninferiority, P=0.0006 for superiority). The incidence of acute pancreatitis (albiglutide 10 patients and placebo 7 patients), pancreatic cancer (6 and 5), medullary thyroid carcinoma (0 and 0), and other serious adverse events did not differ significantly between the two groups. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. (Funded by GlaxoSmithKline; Harmony Outcomes ClinicalTrials.gov number, NCT02465515.) noninferiority; P = 0.06 for superiority). There seems to be variation in the results of existing trials with GLP-1 receptor agonists, which if correct, might reflect drug structure or duration of action, patients studied, duration of follow-up or other factors.

This study showed no significant improvements in clinical outcomes with platelet-function monitoring and treatment adjustment for coronary stenting, as compared with standard antiplatelet therapy without monitoring. (Funded by Allies in Cardiovascular Trials Initiatives and Organized Networks and others; ARCTIC ClinicalTrials.gov number, NCT00827411.).

Background-Shed membrane microparticles circulate in the peripheral blood of nonischemic (NI) patients and patients with myocardial infarction (MI). We investigated whether or not these microparticles would affect endotheliumdependent responses. Methods and Results-Rat aortic rings with endothelium were exposed for 24 hours to circulating microparticles isolated from 7 patients with NI syndromes and 19 patients with acute MI. Endothelium-dependent relaxations to acetylcholine were not affected by high concentrations of microparticles from NI patients (Pϭ0.80). However, significant impairment was observed in preparations exposed to microparticles from patients with MI at low and high concentrations, corresponding to 0.7-fold and 2-fold circulating plasma levels (Pϭ0.05 and 0.001, respectively). Impairment was not affected by diclofenac (Pϭ0.47), nor by the cell-permeable superoxide dismutase mimetic Mn(III)tetra(4-benzoic acid) porphyrin chloride (Pϭ0.33), but it was abolished by endothelium removal or by N monomethyl-L-arginine. Relaxations to the calcium ionophore ionomycin were decreased in rings exposed to microparticles from MI patients (Pϭ0.05 and 0.009 for low and high concentrations, respectively), but microparticles from NI patients had no effect (Pϭ0.81). Finally, high concentrations of microparticles from MI patients affected neither endothelium-independent relaxation to sodium nitroprusside (Pϭ0.59) nor expression of the endothelial nitric oxide synthase (Pϭ0.43). Key Words: endothelium-derived factors Ⅲ nitric oxide synthase Ⅲ arteries Ⅲ vasodilation Ⅲ myocardial infarction M icroparticles generated in vitro from activated platelets or leukocytes stimulate cultured endothelial cells to produce prostacyclin and cytokines and to express adhesion molecules. [1][2][3][4] Recently, apoptotic microparticles have been identified in the circulating blood of patients with acute coronary syndromes and in nonischemic (NI) patients. 5 Acute myocardial infarction (MI) is associated with substantial impairment of vasodilator function in both infarcted myocardium and myocardium perfused by normal vessels. The determinants of this vasomotor dysfunction that may contribute to the extent of ischemia and necrosis after coronary occlusion are not fully elucidated. 6 In the present study, we examined whether or not microparticles circulating in the peripheral blood of NI patients and patients with acute MI affect endothelium-dependent responses in a normal blood vessels. Conclusions-Circulating Methods Patient SelectionWe prospectively included 19 patients with acute MI and 7 NI patients. Patients with MI had clinical, electrocardiographic, and enzymatic changes that were diagnostic of acute MI and were subsequently documented as having significant coronary atherosclerosis by angiography (Table). Control NI patients consisted of 4 patients recruited from the same cardiology department and 3 healthy subjects. Because relaxations did not differ among them (Pϭ0.35), these 7 subjects were pooled into one control NI group (me...

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