Direct Thrombin Inhibition and Stroke Prevention in Elderly Patients With Atrial Fibrillation

Abstract

on behalf of the SPORTIF III, V Investigators 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a DTI studied in the Stroke Prevention using an ORal Thrombin Inhibitor in atrial Fibrillation trials, has been withdrawn, development of other DTIs continues.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 Ն75 (nϭ2804) and Ͻ75 (nϭ4525) 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%, Pϭ0.01) and younger (27% vs 35%, PϽ0.001) patients. Raised alanine aminotransferase values (Ͼ3-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.

Stroke prevention in elderly patients with atrial fibrillation: challenges for anticoagulation

“…The adoption of newer, easier to use and safer anticoagulants might lower the threshold to initiate oral anticoagulation therapy in patients with AF, owing to their better safety ⁄ benefit profile ( Table 1) [59]. The direct thrombin inhibitor ximelagatran appeared to be as effective and safer compared with VKA in elderly patients in the SPORTIF III and SPORTIF V studies, but its development was discontinued because of excessive liver toxicity [60].…”

Ten-year experience with acenocoumarol treatment in an ambulatory cohort of Spanish patients

“…We don't known which is the next step in the future, but the most probable situations are the use of new anticoagulant drugs that do not require monitoring [21][22][23] or the patients' self-managament with portable coagulometers [24,25].…”

Stroke Prevention With Oral Anticoagulation Therapy in Patients With Atrial Fibrillation

“…However, numerical increases in stroke/SE in older compared with younger patients were also reported consistently in the warfarin arms of randomized trials of newer OACs. [31][32][33][34][35] Age is a component of both the CHADS2 and CHA2DS2-VASc stratification schemes for stroke risk in patients with AF; older patients are considered to be at a greater risk of stroke, potentially giving them more to gain from OAC therapy. In CHADS2, a scheme developed using criteria from 2 preexisting systems based on the historical trial cohorts and validated in a registry population, age ≥75 years contributes 1 point to the overall score.…”