Anticoagulation Therapy Your key questions for 2018 clinical - PowerPoint PPT Presentation

Latest Frontiers in Anticoagulation Therapy Your key questions for 2018 clinical practice addressed Supported by an unrestricted educational grant from Course Director Prof. Saskia Middeldorp

Anticoagulation 2017: the key lessons and implications from recent trials John Eikelboom McMaster University www. phri .ca

Rivaroxaban with or without aspirin for cardiovascular prevention COMPASS trial www. phri .ca

Design Stable CAD or PAD 2,200 participants with a primary outcome event Rivaroxaban 2.5 mg bid + Aspirin 100 mg od Rivaroxaban 5 mg bid R Run-in Aspirin 100 mg od (aspirin plus rivaroxaban placebo) Expected mean follow up: 3-4 years www. phri .ca Bosch J, et al. Can J Cardiol 2017; 33: 1027-1035.

Primary outcome: CV death, stroke, MI Cardiovascular Death / Stroke / Myocardial Infarction R + A vs. A: HR 0.76; 95% CI: 0.66-0.86, p<0.0001 0.10 R vs. A: HR 0.90; 95% CI: 0.79-1.03, p=0.12 Aspirin Aspirin 0.08 Rivaroxaban + Aspirin vs. Aspirin HR: 0.76 (0.66-0.86) P=<0.0001 Rivaroxaban Rivaroxaban Rivaroxaban vs. Aspirin HR: 0.90 (0.79-1.03) P=0.12 P= 0.115 Cumulative Hazard Rate Rivaroxaban + Aspirin R + A 0.06 2 0.04 0.02 0.0 0 1 2 3 No. at Risk Rivaroxaban + Aspirin 9152 7904 3912 658 Rivaroxaban 9117 7825 3862 670 Aspirin 9126 7808 3860 669 www. phri .ca Eikelboom J, et al. N Engl J Med 2017; 377: 1319-1330.

Peripheral limb outcomes and mortality R + A Aspirin Rivaroxaban + aspirin N=9,152 N=9,126 vs. aspirin Outcome N N HR p (%) (%) (95% CI) 34 64 0.53 MALE 0.002 (0.4) (0.7) (0.35-0.80) 15 31 0.48 Any amputation 0.02 (0.2) (0.3) (0.26-0.89) 313 378 0.82 Mortality 0.01 (3.4) (4.1) (0.71-0.96) www. phri .ca

A Randomized, Open-Label, Blinded Outcome Assessment Trial Evaluating the Efficacy and Safety of LMWH/Edoxaban versus Dalteparin For Venous Thromboembolism Associated with Cancer Hokusai VTE - Cancer Study G Raskob, N van Es, P Verhamme, M Carrier, M Di Nisio, D Garcia, M Grosso, A Kakkar, M Kovacs, M Mercuri, G Meyer, A Segers, M Shi, T Wang, E Yeo, G Zhang, J Zwicker, J Weitz, H Buller on behalf of the Hokusai-VTE Cancer Investigators Raskob G, et al. N Engl J Med 2017 DOI: 10.1056/NEJMoa1711948.

Hokusai VTE - Cancer Study Design LMWH Edoxaban 60 mg QD* N: ~500 Objectively Confirmed VTE • Stratified randomization for Day 5 R - Bleeding Risk - Dose Adjustment N: ~1000 N: ~500 • PROBE design • 114 sites North America, Europe, Australia, Dalteparin 200 IU/kg Dalteparin 150 IU/kg New Zealand Day 0 Day 30 Month 12 Treatment for up to 12 months (at least 6 months) Efficacy and safety data collected during the entire 12 month study period Independent blind adjudication of all suspected outcomes Severity of major bleeding at presentation also adjudicated Raskob G, et al. N Engl J Med 2017 DOI: 10.1056/NEJMoa1711948.

Primary Endpoint Recurrent VTE or Major Bleeding Raskob G, et al. N Engl J Med 2017 DOI: 10.1056/NEJMoa1711948.