Aging is associated with lower muscle mass and an increase in body fat. We examined whether creatine monohydrate (CrM) and conjugated linoleic acid (CLA) could enhance strength gains and improve body composition (i.e., increase fat-free mass (FFM); decrease body fat) following resistance exercise training in older adults (>65 y). Men (N = 19) and women (N = 20) completed six months of resistance exercise training with CrM (5g/d)+CLA (6g/d) or placebo with randomized, double blind, allocation. Outcomes included: strength and muscular endurance, functional tasks, body composition (DEXA scan), blood tests (lipids, liver function, CK, glucose, systemic inflammation markers (IL-6, C-reactive protein)), urinary markers of compliance (creatine/creatinine), oxidative stress (8-OH-2dG, 8-isoP) and bone resorption (Ν-telopeptides). Exercise training improved all measurements of functional capacity (P<0.05) and strength (P<0.001), with greater improvement for the CrM+CLA group in most measurements of muscular endurance, isokinetic knee extension strength, FFM, and lower fat mass (P<0.05). Plasma creatinine (P<0.05), but not creatinine clearance, increased for CrM+CLA, with no changes in serum CK activity or liver function tests. Together, this data confirms that supervised resistance exercise training is safe and effective for increasing strength in older adults and that a combination of CrM and CLA can enhance some of the beneficial effects of training over a six-month period. Trial Registration. ClinicalTrials.gov NCT00473902

ase presentation: A 76-year-old man with rate-controlled atrial fibrillation (AF), diabetes mellitus, and prior stroke who is receiving warfarin to prevent recurrent stroke presents to the emergency department with chest pain, elevated serum troponin, and an ECG that demonstrates ST depression in the precordial leads. Cardiac catheterization reveals an ulcerated plaque and partially obstructive thrombus in the left circumflex coronary artery. Percutaneous coronary intervention is performed with placement of 2 baremetal stents. What is the optimal antithrombotic therapy? What is the optimal antithrombotic therapy if the patient receives drug-eluting stents instead of bare-metal stents? Efficacy of Antithrombotic Therapy in Patients With AFMeta-analyses of randomized controlled trials in patients with nonvalvular AF indicate that oral vitamin K antagonist (VKA) therapy reduces the risk of stroke or systemic embolism by 64% compared with placebo and by 39% compared with aspirin. 1,2 In the ACTIVE trials (Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events), warfarin reduced the risk of stroke or systemic embolism by 42% compared with dual-antiplatelet therapy with the combination of aspirin and clopidogrel, 3 whereas dual-antiplatelet therapy reduced the risk by 28% compared with aspirin alone. 4 Recently, the RE-LY trial (Randomized Evaluation of Longterm anticoagulant therapY) showed that compared with warfarin the oral direct thrombin inhibitor, dabigatran etexilate given at a dose of 150 mg twice daily reduces stroke with less intracranial bleeding, and dabigatran 110 mg twice daily has similar efficacy with less bleeding. 5 Dabigatran etexilate is not yet approved for stroke prevention in AF.

No abstract

Compared with warfarin, dabigatran is associated with less intracranial hemorrhage, but an increased risk of myocardial infarction. To explore these phenomena, we compared their effects on thrombin generation. Thrombin generation in plasma from 10 patients taking therapeutic doses of warfarin (mean INR 2.6) was compared with that in plasma containing 250 ng/mL dabigatran. Although lag times were similar when thrombin generation was induced by recalcification or with a range of tissue factor concentrations, there was a greater reduction in peak thrombin generation and endogenous thrombin potential in plasma from warfarin-treated patients than in dabigatran-containing plasma. Similar results were obtained when thrombin generation was determined in plasma samples from 18 warfarin or 36 dabigatran treated patients entered into the RE-LY trial. Warfarin suppresses thrombin generation more efficiently than dabigatran. Greater suppression of normal hemostatic mechanisms in the brain and pathological thrombosis at sites of atherosclerotic plaque disruption may explain the higher rate of intracranial bleeding and lower rate of myocardial infarction with warfarin compared with dabigatran.

To cite this article: Paikin JS, Hirsh J, Ginsberg JS, Weitz JI, Chan NC, Whitlock RP, Pare G, Johnston M, Eikelboom JW. Multiple daily doses of acetyl-salicylic acid (ASA) overcome reduced platelet response to once-daily ASA after coronary artery bypass graft surgery: a pilot randomized controlled trial. J Thromb Haemost 2015; 13: 448-56. Summary. Background: The efficacy of ASA for prevention of graft failure following CABG surgery may be limited by incomplete platelet inhibition due to increased post-operative platelet turnover. Objectives: To determine whether acetyl-salicylic acid (ASA) 325 mg once-daily or 81 mg four-times daily overcomes the impaired response to ASA 81 mg once-daily in post-operative coronary artery bypass graft (CABG) patients. Methods: We ran-domized 110 patients undergoing CABG surgery to either ASA 81 mg once-daily, 81 mg four times daily or 325 mg once-daily and compared their effects on serum throm-boxane B 2 (TXB 2) suppression and arachidonate-induced platelet aggregation. Results: One hundred patients were included in the final analysis. Platelet counts fell after surgery , reached a nadir on day 2, and then gradually increased. Although there was near complete suppression of TXB 2 on the second or third post-operative day, TXB 2 levels increased in parallel with the rise in platelet count on subsequent days. This increase was most marked in patients receiving ASA 81 mg once-daily and less evident in those receiving ASA four times daily. On post-operative day 4, (i) median TXB 2 levels were lower with four times daily ASA than with either ASA 81 mg once-daily (1.1 ng/mL; Quartile(Q) Q1,Q3: 0.5, 2.4 and 13.3 ng/mL; Q1,Q3: 7.8, 30.8 ng/mL, respectively; P < 0.0001) or ASA 325 mg once-daily (3.4 ng/mL; Q1,Q3: 2.0, 8.2 ng/mL; P = 0.002), and (ii) ASA given four times daily was more effective than ASA 81 mg once-daily and 325 mg once-daily at suppressing platelet aggregation. Conclusions: Four times daily ASA is more effective than ASA 81 and 325 mg once-daily at suppressing serum TXB 2 formation and platelet aggregation immediately following CABG surgery.