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

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Latest Frontiers in Anticoagulation Therapy

Your key questions for 2018 clinical practice addressed

Course Director

• Prof. Saskia Middeldorp

www.phri.ca

Anticoagulation 2017: the key lessons and implications from recent trials

John Eikelboom McMaster University

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Rivaroxaban with or without aspirin for cardiovascular prevention

COMPASS trial

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Design

R

Rivaroxaban 2.5 mg bid + Aspirin 100 mg od Aspirin 100 mg od Rivaroxaban 5 mg bid Expected mean follow up: 3-4 years Run-in (aspirin plus rivaroxaban placebo)

Stable CAD or PAD 2,200 participants with a primary outcome event

Bosch J, et al. Can J Cardiol 2017; 33: 1027-1035.

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Cumulative Hazard Rate 0.0 0.02 0.04 0.06 0.08 0.10 1 2 3

9152 7904 3912 658 9117 7825 3862 670 9126 7808 3860 669

• No. at Risk

Rivaroxaban + Aspirin Rivaroxaban Aspirin

Rivaroxaban + Aspirin Rivaroxaban Aspirin

Rivaroxaban + Aspirin vs. Aspirin HR: 0.76 (0.66-0.86) P=<0.0001 Rivaroxaban vs. Aspirin HR: 0.90 (0.79-1.03) P= 0.115

Cardiovascular Death / Stroke / Myocardial Infarction

Primary outcome: CV death, stroke, MI

Eikelboom J, et al. N Engl J Med 2017; 377: 1319-1330.

P=0.12 2

R + A vs. A: HR 0.76; 95% CI: 0.66-0.86, p<0.0001 R vs. A: HR 0.90; 95% CI: 0.79-1.03, p=0.12 Aspirin R + A Rivaroxaban

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Peripheral limb outcomes and mortality

Outcome R + A N=9,152 Aspirin N=9,126 Rivaroxaban + aspirin

• vs. aspirin

N (%) N (%) HR (95% CI) p MALE 34 (0.4) 64 (0.7) 0.53 (0.35-0.80) 0.002 Any amputation 15 (0.2) 31 (0.3) 0.48 (0.26-0.89) 0.02 Mortality 313 (3.4) 378 (4.1) 0.82 (0.71-0.96) 0.01

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

• n behalf of the Hokusai-VTE Cancer Investigators

Hokusai VTE - Cancer Study

A Randomized, Open-Label, Blinded Outcome Assessment Trial Evaluating the Efficacy and Safety of LMWH/Edoxaban versus Dalteparin For Venous Thromboembolism Associated with Cancer

Raskob G, et al. N Engl J Med 2017 DOI: 10.1056/NEJMoa1711948.

Hokusai VTE - Cancer Study Design

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

N: ~1000

Objectively Confirmed VTE

• Stratified randomization for
• Bleeding Risk
• Dose Adjustment
• PROBE design
• 114 sites North America,

Europe, Australia, New Zealand

R

Dalteparin 200 IU/kg

Day 30 Day 0

Dalteparin 150 IU/kg Edoxaban 60 mg QD* Day 5 LMWH

Month 12 N: ~500 N: ~500

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.