Stroke prevention: Age alone does not rule out warfarin

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PURLs

Stroke prevention: Age alone does not rule out warfarin

J Fam Pract. 2007 November;56(11):902-906

References

1. Mant J, Hobbs FD, Fletcher K, et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet 2007;370:493-503.

2. Singer DE, Albers GW, Dalen JE, et al. Antithrombotic therapy in atrial fibrillation: The seventh ACCP (American College of Chest Physicians) conference on antithrombotic and thrombolytic therapy. Chest 2004;126:429S-456S.

3. Fuster V, Rydén LE, Cannom DS, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation—executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation). J Am Coll Cardiol 2006;48:854-906.

4. Go AS, Hylek EM, Borowsky LH, et al. Warfarin use among ambulatory patients with non-valvular atrial fibrillation: The Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) study. Ann Intern Med 1999;131:927.-

5. Hart RG, Pearce LA, Aguilar MI. Meta-analysis: Antithrombotic therapy to prevent stroke in patients who have non-valvular atrial fibrillation. Ann Intern Med 2007;146:857-867.

6. Hylek EM, Evans-Molina C, Shea C, et al. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 2007;115:2689-2696.

7. POEM: Bleeding risk with warfarin is high among the elderly. J Fam Pract 2007;6:709.-

8. Garcia D, Hylek E. Stroke prevention in elderly patients with atrial fibrillation. Lancet 2007;370:460-461.

9. Perez-Gomez F, Alegria E, Bejon J, et al. Comparative effects of antiplatelet, anticoagulant, or combined therapy in patients with valvular and non-valvular atrial fibrillation: a randomized multicenter study. J Am Coll Cardiol 2004;44:1557-1556.

10. Rash A, Downes T, Portner R, et al. A randomized controlled trial of warfarin versus aspirin for stroke preventions in octogenarians with atrial fibrillation (WASPO). Age Ageing 2007;36:151-156.

11. Gullov AL, Koeford BG, Petersen P, et al. Fixed minidose warfarin and aspirin alone and in combination vs adjusted-dose warfarin for stroke prevention in atrial fibrillation. Arch Intern Med 1998;158:1513-1521.

12. Witt DM, Sadler MA, Shanahan RL, et al. Effect of a centralized clinical pharmacy anticoagulation service on outcomes of anticoagulation therapy. Chest 2005;127:1515-1522.

13. Wurster M, Doran T. Anticoagulation management: a new approach. Disease Management 2006;9:201-209.

14. Dorfman DM, Goonan EM, Boutilier MK, et al. Point-of-care (POC) versus central laboratory instrumentation for monitoring oral anticoagulation. Vasc Med 2005;10:23-27.

Caveats: Consider the evidence on benefits and risks

Major bleeding from warfarin is a concern, especially in the elderly. A recent cohort study⁶ (summarized as a POEM in this journal⁷) reported high rates of major bleeding (13.1 per hundred person-years or 13.1%) in patients ≥80 years of age during their first year of warfarin therapy. Despite the high risk of bleeding events in this cohort study, there was considerable benefit from warfarin therapy.

None of the patients who remained on warfarin had a thrombotic stroke (personal communication with Dr Hylek by the author). The expected rate of thrombotic stroke is in the range of 5% to 6% per year in this high-risk group.

Furthermore, most of the bleeding events were gastrointestinal and did not lead to catastrophic outcomes.

FAST TRACK

Keep the patient’s INR under 3.0 and watch for signs of bleeding, especially in the first 90 days of warfarin therapy

Do not add warfarin to aspirin in patients >75 years

Dr Hylek also noted that 40% of the patients in their cohort study were taking both warfarin and aspirin, and, although her study did not have sufficient power to detect a difference, prior studies noted increased risk of bleeding with this combination compared to warfarin alone.^8,9 For this reason we think the combination of warfarin and aspirin should be avoided in patients over 75.

Target INR <3

Our caveat is the same as the POEM author’s conclusion:⁷ Patients over 80 should be carefully monitored to keep the INR below 3.0 or for signs of bleeding, especially in the first 90 days of therapy when bleeding is more likely to occur.

A final point that the BAFTA authors make, which is worth repeating here, is that the prior studies showing an increased risk of bleeding complications had INR target rates of 4 to 5, whereas the target in this study was 2 to 3. Two previous studies that also compared aspirin to warfarin with an INR goal of 2 to 3 similarly showed no difference in major bleeding between the 2 groups.^10,11

Challenges to Implementation: Meticulous monitoring, patient education

Managing warfarin therapy requires meticulous care to avoid complications and optimize treatment effect.
Patients may be reluctant to take warfarin because they may fear bleeding.
Patients who do agree to take warfarin need education about possible medication interactions, the need for regular INR monitoring, dosage changes, and dietary issues (eg, maintaining a consistent intake of foods containing vitamin K).

Contraindications

Contraindications to the use of warfarin include hypersensitivity to warfarin, severe hepatic disease, alcoholism, recent trauma or surgery, history of falling or significant risk of falls, and active gastrointestinal, respiratory, or genitourinary bleeding.

INR testing systems

Several randomized trials support the use of monitoring systems such as a pharmacist managed anticoagulation service or decision support software, both of which can improve the percentage of patients with therapeutic INR values.^12,13

Using point-of-care INR tests in the office provides immediate results which allow for more timely adjustments of warfarin dose.¹⁴

PURLs methodology

This study was selected and evaluated using the Family Physician Inquiries Network’s Priority Updates from the Research Literature Surveillance System (PURLs) methodology. The criteria and findings leading to the selection of this study as a PURL can be accessed here.