Letter Regarding Article by Hylek et al, “Major Hemorrhage and Tolerability of Warfarin in the First Year of Therapy Among Elderly Patients With Atrial Fibrillation”
To the Editor:
We read with great interest the recent publication by Hylek et al1 in which they concluded that the rate of bleeding complications during warfarin therapy was substantially higher than previously reported in elderly patients with atrial fibrillation. They emphasize that published rates of major hemorrhage derived from younger noninception cohorts underestimate the bleeding that occurs in clinical practice, and the higher rate of bleeding in their study is attributable to the higher risk of bleeding in the early phase of warfarin therapy and the advanced age of their study subjects. However, the results are not necessarily generalizable to other clinical settings, because the patients enrolled in this cohort have more risk factors for bleeding than representative patients receiving warfarin in clinical practice.
First, the patients received aspirin combined with warfarin at a remarkably higher rate (40%) than reported previously.2 The frequent use of aspirin may contribute to the higher rate of bleeding in patients receiving warfarin, because previous studies have demonstrated that combined anticoagulant-antiplatelet use increases bleeding risk without additive prevention of thromboembolic events. In recent trials comparing ximelagatron and warfarin, the combination therapy of aspirin with either ximelagatron or warfarin did not reduce the risk of stroke, systemic embolism, or myocardial infarction, but the addition of aspirin to warfarin or ximelagatron was associated with increased risk of bleeding, which was especially obvious when aspirin and warfarin were combined.3
Second, the study included patients receiving warfarin in spite of their potential contraindications for anticoagulation, such as active malignancy, prior bleeding, and dementia. In general, patients with risk factors for bleeding should be considered as ineligible for anticoagulation.
When physicians use warfarin in eligible patients at high risk but without contraindications, thromboembolism-associated atrial fibrillation can be adequately and safely prevented even in elderly patients. In fact, recent inception cohorts in which warfarin was newly started in elderly patients without contraindications or concomitant use of antiplatelets reported lower rates of major bleeding (<3% per 100 person-years)4,5 than the study by Hylek et al (7.2% per 100 person-years).1
Hylek EM, Evans-Molina C, Shea C, Henault LE, Regan S. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation. 2007; 115: 2689–2696.
Gorelick PB. Combining aspirin with oral anticoagulant therapy: is this a safe and effective practice in patients with atrial fibrillation? Stroke. 2007; 38: 1652–1654.
Kalra L, Yu G, Perez I, Lakhani A, Donaldson N. Prospective cohort study to determine if trial efficacy of anticoagulation for stroke prevention in atrial fibrillation translates into clinical effectiveness. BMJ. 2000: 320; 1236–1239.
Ruiz Ortiz M, Romo Penas E, Franco Zapata MF, Mesa Rubio D, Anguita Sanchez M, Lopez Granados A, Arizon del Prado JM, Valles Belsue F. Oral anticoagulation in patients aged 75 years or older with chronic non-valvar atrial fibrillation: effectiveness and safety in daily clinical practice. Heart. 2005; 91: 1225–1226.