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Direct Thrombin Inhibition and Stroke Prevention in Elderly Patients With Atrial Fibrillation
Experience From the SPORTIF III and V Trials
Gary A. Ford, MD; Anna Maria Choy, MD; Prakash Deedwania, MD; Dean G. Karalis, MD; Carl-Johan Lindholm, MD; Wladyslaw Pluta, MD; Lars Frison, PhD; S. Bertil Olsson, MD on behalf of the SPORTIF III, V Investigators
From the Institute for Ageing and Health (G.A.F.), University of Newcastle upon Tyne, Newcastle upon Tyne, England; the Division of Medicine and Therapeutics (A.M.C.), Ninewells Hospital and Medical School, Dundee, Scotland; the Department of Cardiology (P.D.), VA Medical Center/UCSF School of Medicine, San Francisco, Calif; the Department of Cardiology (D.G.K.), Drexel University College of Medicine, Philadelphia, Pa; the Department of Cardiology (C.-J.L., S.B.O.), University Hospital, Lund, Sweden; the Department of Cardiology (W.P.), Wojewódzkie Centrum Medyczne, Opole, Poland; and AstraZeneca R&D M鰈ndal (L.F.), M鰈ndal, Sweden.
Background and Purpose— Warfarin prevents stroke in atrial fibrillation (AF); however, concerns regarding international normalized ratio control and hemorrhage limit its use in the elderly. The oral direct thrombin inhibitors (DTIs) are potential alternatives to warfarin, offering fixed dosing without drug and dietary interactions and the need for international normalized ratio monitoring. Although ximelagatran, a DTI studied in the Stroke Prevention using an ORal Thrombin Inhibitor in atrial Fibrillation trials, has been withdrawn, development of other DTIs continues. We report our experience in elderly high-risk AF patients on ximelagatran compared with warfarin therapy.
Methods— Data from patients with AF and stroke risk factors randomized in Stroke Prevention using an ORal Thrombin Inhibitor in atrial Fibrillation III and V trials to ximelagatran or warfarin were analyzed for stroke/systemic emboli, bleeding, and raised alanine aminotransferase levels in those 75 (n=2804) and <75 (n=4525) years.
Results— Ximelagatran was as effective as warfarin in reducing stroke/systemic emboli in the elderly (2.23%/y with ximelagatran vs 2.27%/y with warfarin) as in younger patients (1.25%/y vs 1.28%/y). Total bleeds were significantly lower with ximelagatran compared with warfarin in elderly (40% vs 45%, P=0.01) and younger (27% vs 35%, P<0.001) patients. Raised alanine aminotransferase values (>3-fold elevation) among ximelagatran patients were more common in older (7.5% old vs 5.3% young) patients, particularly women (9.5% elderly women vs 6.1% elderly men).
Conclusions— In high-risk elderly AF patients, ximelagatran is as effective as warfarin with less bleeding, but alanine aminotransferase elevations are common, particularly in elderly women. Oral DTIs for stroke prevention show promise in elderly patients.
Key Words: atrial fibrillation - elderly - direct thrombin inhibitors - stroke - ximelagatran
Stroke. 2007;38:2965-2971
http://stroke.ahajournals.org/cgi/content/abstract/38/11/2965 |
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发表于 2007-11-12 18:52:20