Direct thrombin inhibition and stroke prevention in elderly patients with atrial fibrillation: experience from the SPORTIF III and V Trials.
OBJECTIVE
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a DTI studied in the Stroke Prevention using an ORal Thrombin Inhibitor in atrial Fibrillation trials, has been withdrawn, development of other DTIs continues.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 >or=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.
Ford
Gary A
GA
Institute for Ageing and Health, University of Newcastle upon Tyne, Newcastle upon Tyne, England.
Choy
Anna Maria
AM
Deedwania
Prakash
P
Karalis
Dean G
DG
Lindholm
Carl-Johan
CJ
Pluta
Wladyslaw
W
Frison
Lars
L
Olsson
S Bertil
SB
D000284:Administration, Oral; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000150:complications*; D001384:Azetidines / Q000008:administration & dosage* / Q000009:adverse effects; D001596:Benzylamines / Q000008:administration & dosage* / Q000009:adverse effects; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D004311:Double-Blind Method; D004617:Embolism / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D005260:Female; D006801:Humans; D020767:Intracranial Thrombosis / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D012727:Sex Characteristics; D012737:Sex Factors; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D013917:Thrombin / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects
D000925:Anticoagulants; D001384:Azetidines; D001596:Benzylamines; C426686:ximelagatran; D014859:Warfarin; D000410:Alanine Transaminase; D013917:Thrombin