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Vol 59: october • octobre 2013

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Canadian Family PhysicianLe Médecin de famille canadien

1075

Tools for Practice

Tools for Practice articles in Canadian Family Physician (CFP) are adapted from articles published on the Alberta College of Family Physicians (ACFP) website, summarizing medical evidence with a focus on topical issues and practice-modifying information. The ACFP summaries and the series in CFP are coordinated by Dr G. Michael Allan, and the summaries are co-authored by at least 1 practising family physician and are peer reviewed. Feedback is welcome and can be sent to toolsforpractice@cfpc.ca.

Archived articles are available on the ACFP website: www.acfp.ca.

Use of ASA after warfarin for unprovoked VTE

G. Michael Allan

MD CCFP

Hoan Linh Banh

PharmD

Jonathan Ference

PharmD BCPS

Clinical question

When stopping oral anticoagulants (like warfarin) after treatment of venous thromboembolism (VTE), should acetylsalicylic acid (ASA) be offered?

Bottom line

Once warfarin treatment for unprovoked VTE is com- plete, low-dose ASA prevents recurrent VTE for 1 in 19 patients over 2.5 years with no increase in major bleeding. Acetylsalicylic acid does not replace warfarin or novel anticoagulants for the initial treatment of VTE.

Evidence

Two randomized controlled trials (WARFASA1 and ASPIRE2) looked at patients with their first unprovoked VTE (deep vein thrombosis, pulmonary embolism, or both) treated with warfarin for approximately 12 months, then randomized to receive ASA (100 mg daily) or placebo.

• Pooled results2 (N = 1225, mean age 57, 57% men, fol- lowed for approximately 2.5 years) found the following:

-A statistically significant (P < .05) reduction in

—recurrence of VTE: 19.1% for placebo versus 13.8%

for ASA, number needed to treat of 19; and —major vascular events (VTE, myocardial infarction,

stroke, or death from cardiovascular causes): 22.4%

for placebo versus 15.9% for ASA, number needed to treat of 14.

-No difference in (data pooled and analyzed by author G.M.A.) major bleeds (1.2% for placebo vs 1.5% for ASA) or mortality (3.8% for placebo vs 3.6% for ASA).

• Limitations: Protocol change (in WARFASA, likely to help find statistical significance); shortfall in recruit- ment (eg, ASPIRE “aspired” to recruit 3000 patients).

Context

• Overall risk of recurrent VTE after warfarin treatment is approximately 7% to 11% in the first year.3,4

-Risks continue over time: approximately 15% to 20%

at 3 years and 30% at 5 years.3,4

-Men and those with unprovoked VTE have about 2 times higher recurrence risk than women or those with provoked VTE.3,4

• While ASA reduces the relative risk of recurrent VTE by 32%,1,2 warfarin and novel anticoagulants (eg, riva- roxaban) reduce the risk by about 80%.5-8

-In patients with unprovoked VTE, anticoagulation will reduce recurrent VTE to about 4% (from about 30%).9 -Anticoagulation will increase major bleeds9 by 2% to

5% in those at low to moderate risk of bleeding and by about 20% in those at high risk.

—High risk of bleeding is 2 or more bleeding risk factors (eg, age older than 65, cancer, anemia, thrombocytopenia, liver or renal failure, anti- platelet therapy, etc).

-Fatality rates for recurrent VTE are about 3.6% (vs 11.3% for major bleeds).9

Implementation

The duration of anticoagulation (warfarin or novel antico- agulants) should balance VTE recurrence and bleed risk.9 The 2012 American College of Chest Physicians guidelines9 advise 3 months of therapy for patients with provoked VTE (eg, during surgery), except in active cancer when antico- agulation should be extended if possible; and 3 months of therapy and consideration of extended therapy for patients with unprovoked VTE. If bleeding risk is low to moder- ate, extend therapy; if risk is high, consider stopping at 3 months. How long to extended therapy is unclear from the guidelines, but therapy could be indefinite if benefit out- weighs risk, leaving plenty of room for clinical judgment.

Acetylsalicylic acid is not a substitute for initial VTE treat- ment with warfarin or novel anticoagulants, but it should be considered when anticoagulation is discontinued.

Drs Allan and Banh are Associate Professors in the Department of Family Medicine at the University of Alberta in Edmonton. Dr Ference is Associate Professor of Pharmacy Practice at the Nesbitt College of Pharmacy and Nursing at Wilkes University in Wilkes-Barre, Pa, and Director of Pharmacotherapy Education for the Wright Center for Graduate Medical Education Family Medicine Residency Program.

The opinions expressed in Tools for Practice articles are those of the authors and do not necessarily mirror the perspective and policy of the Alberta College of Family Physicians.

references

1. Becattini C, Agnelli G, Schenone A, Eichinger S, Silingardi M, Silingardi M, et al. Aspirin for preventing the recurrence of venous thromboembolism. N Engl J Med 2012;366:1959-67.

2. Brighton TA, Eikelboom JW, Mann K, Milster R, Gallus A, Ockelford P, et al. Low-dose aspi- rin for preventing recurrent venous thromboembolism. N Engl J Med 2012;367:1979-87.

3. Douketis J, Tosetto A, Marcucci M, Baglin T, Cosmi B, Cushman M, et al. Risk of recur- rence after venous thromboembolism in men and women: patient level meta-analysis.

BMJ 2011;342:d813.

4. Prandoni P, Noventa F, Ghirarduzzi A, Pengo V, Bernardi E, Pesavento R, et al. The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients. Haematologica 2007;92:199-205.

5. Hutten BA, Prins MH. Duration of treatment with vitamin K antagonists in symptomatic venous thromboembolism. Cochrane Database Syst Rev 2006;(1):CD001367.

6. Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H; EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010;363:2499-510.

7. Schulman S, Kearon C, Kakkar AK, Schellong S, Eriksson H, Baanstra D, et al. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med 2013;368:709-18.

8. Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 2013;368:699-708.

9. Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ, et al.

Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physician evidence-based clinical practice guidelines. Chest 2012;141(2 Suppl):e419S-94S.

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