Decisions regarding the use of triple therapy should take into account the balance between thromboembolism and bleeding risk in individual patients
The combined use of warfarin and dual antiplatelet therapy (aspirin plus clopidogrel) — so-called triple therapy — is a challenging management problem in patients with a coronary stent who also have an indication for oral anticoagulation. One of the most common clinical scenarios is a patient with atrial fibrillation (AF) who undergoes percutaneous coronary intervention with stenting. Guidelines for antithrombotic therapy recommend that patients with AF who are at high risk of stroke (ie, prior history of stroke or more than one of: age ≥ 75 years, hypertension, diabetes, and congestive cardiac failure) receive warfarin;1 and guidelines for percutaneous coronary intervention management recommend dual antiplatelet therapy in all stent patients to prevent stent thrombosis.2 Both warfarin and clopidogrel increase the risk of bleeding in patients treated with aspirin, and combining all three drugs can be expected to further increase bleeding risk. However, the efficacy and safety of triple therapy have not been evaluated in randomised controlled trials.
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- 1. Fuster V, Rydén LE, Cannom DS, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation. 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: e149-e246.
- 2. King SB 3rd, Smith SC Jr, Hirshfeld JW Jr, et al. 2007 focused update of the ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines: 2007 Writing Group to Review New Evidence and Update the ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention, writing on behalf of the 2005 Writing Committee. Circulation 2008; 117: 261-295.
- 3. Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 2007; 146: 857-867.
- 4. Connolly SJ, Pogue J, Hart RG, et al. Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med 2009; 360: 2066-2078.
- 5. Connolly S, Pogue J, Hart R, et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet 2006; 367: 1903-1912.
- 6. Mehta SR, Yusuf S; Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) Study Investigators. The Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) trial programme; rationale, design and baseline characteristics including a meta-analysis of the effects of thienopyridines in vascular disease. Eur Heart J 2000; 21: 2033-2041.
- 7. Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 2005; 293: 2126-2130.
- 8. Paikin JS, Wright DS, Mehta SR, et al. Triple antithrombotic therapy in patients with atrial fibrillation and coronary artery stents. Circulation 2010. In press.
- 9. Holmes DR Jr, Kereiakes DJ, Kleiman NS, et al. Combining antiplatelet and anticoagulant therapies. J Am Coll Cardiol 2009; 54: 95-109.
- 10. Gage BF, Waterman AD, Shannon W, et al. Validation of clinical classification schemes for predicting stroke. JAMA 2001; 285: 2864-2870.
- 11. Schulman S, Beyth RJ, Kearon C, et al. Hemorrhagic complications of anticoagulant and thrombolytic treatment: American College of Chest Physicians evidence-based clinical practice guidelines (8th ed). Chest 2008; 133: 257S-298S.
- 12. Patrono C, Baigent C, Hirsh J, et al. Antiplatelet drugs: American College of Chest Physicians evidence-based clinical practice guidelines (8th ed). Chest 2008; 133: 199S-233S.
- 13. Bhatt DL, Scheiman J, Abraham NS, et al. ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use. A report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. Circulation 2008; 118: 1894-1909.
- 14. Juurlink DN, Gomes T, Ko DT, et al. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ 2009; 180: 713-718.
- 15. Ho PM, Maddox TM, Wang L, et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA 2009; 301: 937-944.
- 16. O’Donoghue ML, Braunwald E, Antman EM, et al. Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials. Lancet 2009; 374: 989-997.
Shamir Mehta has been paid consultancy fees by Eli Lilly, AstraZeneca and sanofi-aventis, and has received a research grant from sanofi-aventis. John Eikelboom has been paid consultancy fees and/or received honoraria from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Corgenix, Daiichi Sankyo, Eisai, Eli Lilly, GlaxoSmithKline, Haemoscope, McNeil, and sanofi-aventis, and grants or in-kind support from Accumetrics, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Corgenix, Dade Behring, GlaxoSmithKline and sanofi-aventis. The views expressed in this article are solely ours, and are not influenced by any affiliated organisations.