CADTH Rapid Response Report: ASA for Venous Thromboembolism Prophylaxis: Evidence for Clinical Benefit and Harm

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1 CADTH Rapid Response Report: ASA for Venous Thromboembolism Prophylaxis: Evidence for Clinical Benefit and Harm P. Timothy Pollak, MD, PhD University of Calgary Rocky Mountain/ACP Internal Medicine Meeting, November 24, 2011

2 Objectives: Understand the difference between clot formation in the arterial and venous circulation. Review the association of venous thrombosis with surgical diagnoses and precedures. Address the conflicting recommendations regarding the use of ASA in prevention of DVT and PE in patients undergoing Hip and Knee replacement. See 23 June 2011 Report from CADTH Canadian Agency for Drugs and Technologies in Health at:

3 Arterial and Venous Thrombosis Venous RBC and fibrin-rich red clot crystalizing in low flow states Arterial platelet-rich white clot, cytokine activated sticking to atherosclerotic/inflrammatory lesions in high flow states Vascular release of interleukins-6 and -8 Inflammation and platelet activation participate in venous thrombogenesis but to a lesser extent than in arterial clotting Anti-platelet therapy effective in arterial>venous thrombosis

4 Surgical Venous Thrombosis VTE promoted by venous stasis, vascular injury +/- hypercoagulability = orthpediac surgical conditions = Rudolf Virchow's Triad Hip # DVT rate 27% proximal, 50% total Hip # Fatal PE rate % Total hip/knee arthroplasty has lower rate Prophylaxis choices: warfarin, LMW heparin, and pentasaccharides (fondaparinux); increase bleed risk Am Coll Chest Phys (ACCP) and Am Acad Ortho Surg (AAOS) do NOT agree on use of ASA in prevention of DVT and PE in ortho patients

5 VTE Prophylaxis with ASA? Benefits of ASA: cost, oral dosing, no monitoring Guidelines do NOT agree on use of ASA for prophylaxis for Total Hip/Knee of Hip # surgery Q1. What is the clinical evidence on ASA for venous thromboembolism prophylaxis? Q2. What are the clinical benefits and harms of using ASA for venous thromboembolism prophylaxis? KEY MESSAGE: There may be a place for ASA-based VTE prophylaxis in some patients undergoing orthopedic surgeries, but evidence is limited

6 CADTH Evaluation of ASA 245 citations provided 3 appropriate studies 1. meta-analysis of 14 RCTs 2. prospective cohort 3. retrospective cohort study (93,840 pt in 307 cntr) 1. VTE rates with ASA similar to VKA, LMWH and pentasaccharides & surgical site bleeds lower 2. warfarin had lower PE and VTE rates vs. ASA & no differences major bleeds or death between groups 3. VTE rates with ASA similar to injectable VTEP & lower than warfarin recipients, but same risk of bleeding, infection or death between groups Figures available at:

7 Question Design

8 Characteristics of 3 Reports Studied

9 Evidence from 3 Reports Studied

10 ASA Guidelines Likely to Change confirms the efficacy of VKA and lack of effect of ASA treatment on the risk of stroke/thromboembolism. the risk of bleeding was increased with both VKA and ASA treatment, but the net clinical benefit was in favour of VKA

11 CASES >> Canadian Approaches to Stroke PrEvention In Atrial ArrhythmiaS Bleeding Associated with Combination Antiplatelet and Anticoagulant Therapy (Analysis of Registry Data) Combination therapy with anticoagulant and antiplatelet agents is associated with increased risk of bleeding and is proportional to the number of drugs used A Increased Risk 1. Sorensen R, et al. Lancet 2009;374:

12 Summary Efficacy: ASA less active in preventing thrombosis, more VTE, less bleeding Uncertainty: May be useful in some patients for VTE prophylaxis, but evidence poor zero-order clearance of ASA, long effect of irreversible acetylation of serine on COX For VTE, I would still bet on anticoagulation over anti-platelet therapy: NEW AGENTS?

13 The (dead) End