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.

BACKGROUND Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. OBJECTIVES In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. METHODS ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was <70 mg/dL (median 69.4 mg/dL; interquartile range: 64.3–74.0 mg/dL); in 14,573 patients (77.0%), both determinations were ≥70 mg/dL (median 94.0 mg/dL; interquartile range: 83.2–111.0 mg/dL). RESULTS In the lower LDL-C subgroup, MACE rates were 4.2 and 3.1 per 100 patient-years among placebo-treated patients with baseline lipoprotein(a) greater than or less than or equal to the median (13.7 mg/dL). Corresponding adjusted treatment hazard ratios were 0.68 (95% confidence interval [Cl]: 0.52–0.90) and 1.11 (95% Cl: 0.83–1.49), with treatment-lipoprotein(a) interaction on MACE ( P interaction = 0.017). In the higher LDL-C subgroup, MACE rates were 4.7 and 3.8 per 100 patient-years among placebo-treated patients with lipoprotein(a) >13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% Cl: 0.72–0.92) and 0.89 (95% Cl: 0.75–1.06), with P interaction = 0.43. CONCLUSIONS In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402 )

In this multicentre study, 90 patients who left hospital in sinus rhythm after electroconversion of atrial fibrillation were randomized to double-blind treatment with either disopyramide (n = 44) or placebo (n = 46). The groups were comparable regarding age and sex distribution, duration of atrial fibrillation, heart volume and NYHA-classification. Life-table analysis was used to estimate the percentage of patients still in sinus rhythm and tolerating treatment at control visits after 1, 3, 6, 9 and 12 months. After 1 month there was already a significant difference (P less than 0.01) between the two groups (disopyramide 70%, placebo 39%), a difference that was still remaining after 12 months (disopyramide 54%, placebo 30%). Twenty-four patients, all relapsing to atrial fibrillation before six months on placebo, were converted to sinus rhythm once again. They were then treated with disopyramide in an open manner and after 12 months 37% were still in sinus rhythm. From the results of this study, disopyramide seems to be a useful drug in maintaining sinus rhythm after electroconversion of atrial fibrillation.

ABSTRACT. The diagnostic efficiency of 99Tcm‐plasmin test was evaluated by X‐ray contrast phlebography in 110 consecutive patients with suspected deep vein thrombosis (DVT). The test was positive in 50 of 55 patients with DVT (sensitivity 91%) and negative in 18 of 55 without DVT (specificity 33%). The positive plasmin test in patients without DVT was in most cases due to another inflammatory process or a post‐thrombotic state. The 99Tcm‐plasmin test is a rapid and sensitive screening method for the diagnosis of DVT, but as it is based on comparison between the legs, it may be unreliable in cases of bilateral thrombosis. The low specificity makes it less valuable in patients with concomitant inflammatory disease or previous thrombosis in either leg. When the plasmin test is positive, the diagnosis of DVT should in most cases be confirmed by X‐ray contrast phlebography.

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