Objectives: Hyperglycaemia has been associated with increased platelet reactivity and impaired prognosis in patients with acute coronary syndrome (ACS). Whether platelet reactivity can be reduced by lowering glucose in this setting is unknown. The aim of this study was to assess the functional impact of intensive glucose control with insulin on platelet reactivity in patients admitted with ACS and hyperglycaemia. Methods: This is a prospective, randomised trial evaluating the effects of either intensive glucose control (target glucose 80–120 mg/dl) or conventional control (target glucose 180 mg/dl or less) with insulin on platelet reactivity in patients with ACS and hyperglycaemia. The primary endpoint was platelet aggregation following stimuli with 20 μM ADP at 24 h and at hospital discharge. Aggregation following collagen, epinephrine and thrombin receptor-activated peptide, as well as P2Y₁₂ reactivity index and surface expression of glycoprotein IIb/IIIa and P-selectin were also measured. Results: Of the 115 patients who underwent random assignment, 59 were assigned to intensive and 56 to conventional glucose control. Baseline platelet functions and inhospital management were similar in both groups. Maximal aggregation after ADP stimulation at hospital discharge was lower in the intensive group (47.9±13.2% vs 59.1±17.3%; p=0.002), whereas no differences were found at 24 h. Similarly all other parameters of platelet reactivity measured at hospital discharge were significantly reduced in the intensive glucose control group. Conclusions: In this randomised trial, early intensive glucose control with insulin in patients with ACS presenting with hyperglycaemia was found to decrease platelet reactivity. Clinical Trial Registration Number: http://www.controlledtrials.com/ISRCTN35708451/ISRCTN35708451.

Direct oral anticoagulants (DOACs) have been demonstrated to be more effective and safer than vitamin-K antagonist (VKA) for stroke prevention in patients with nonvalvular atrial fibrillation (AF). This meta-analysis aims to assess the effect of DOACS vs. VKA in patients ≥ 80 and AF. Primary endpoints were stroke or systemic embolism and all-cause death. Secondary endpoints included major bleeding, intracranial bleeding, and gastrointestinal bleeding. A random-effects model was selected due to significant heterogeneity. A total of 147,067 patients from 16 studies were included, 71,913 (48.90%) treated with DOACs and 75,154 with VKA (51.10%). The stroke rate was significantly lower in DOACs group compared with warfarin group (Relative risk (RR): 0.72; 95% confidence interval (CI): 0.63–0.82; p < 0.001). All-cause mortality was significantly lower in DOACs group compared with warfarin group (RR: 0.82; 95% CI: 0.70–0.96; p = 0.012). Compared to warfarin, DOACs were not associated with reductions in major bleeding (RR: 0.85, 95% CI 0.69–1.04; p = 0.108) or gastrointestinal bleeding risk (RR: 1.08, 95% CI 0.76–1.53; p = 0.678) but a 43% reduction of intracranial bleeding (RR: 0.47, IC 95% 0.36–0.60; p < 0.001) was observed. Our meta-analysis demonstrates that DOACs are effective and safe with statistical superiority when compared with warfarin in octogenarians with AF.

Background—: Prasugrel and ticagrelor, new P2Y ₁₂ -adenosine diphosphate receptor antagonists, are associated with greater pharmacodynamic inhibition and reduction of cardiovascular events compared with clopidogrel in patients with an acute coronary syndrome. However, evidence is lacking about the effects of achieving faster and stronger cyclooxygenase inhibition with intravenous lysine acetylsalicylate (LA) compared with oral aspirin on prasugrel-inhibited platelets. Methods and Results—: This was a prospective, randomized, single-center, open, 2-period crossover platelet function study conducted in 30 healthy volunteers. Subjects were randomly assigned to receive a loading dose of intravenous LA 450 mg plus oral prasugrel 60 mg or loading dose of aspirin 300 mg plus prasugrel 60 mg orally in a crossover fashion after a 2-week washout period between treatments. Platelet function was evaluated at baseline, 30 minutes, 1 h, 4 h, and 24 h using light transmission aggregometry and vasodilator-stimulated phosphoprotein phosphorylation. The primary end point of the study, inhibition of platelet aggregation after arachidonic acid 1.5 mmol/L at 30 minutes, was significantly higher in subjects treated with LA compared with aspirin: 85.3% versus 44.3%, respectively, P =0.003. This differential effect was observed at 1 hour ( P =0.002) and 4 hours ( P =0.048), but not at 24 hours. Subjects treated with LA presented less variability and faster and greater inhibition of platelet aggregation with arachidonic acid compared with aspirin. Conclusions—: The administration of intravenous LA resulted in a significant reduction of platelet reactivity compared with oral aspirin on prasugrel-inhibited platelets. Loading dose of LA achieves an earlier platelet inhibition and with less variability than aspirin. Clinical Trial Registration—: URL: http://www.clinicaltrials.gov . Unique identifier: NCT02243137.