Palle Petersen

Ximelagatran versus warfarin forstroke prevention in patientswith nonvalvular atrial fibrillation: SPORTIF ii: a dose-guiding, tolerability, and safety study

OBJECTIVES We sought to compare the tolerability and safety of three fixed doses of ximelagatran versus warfarin in patients with nonvalvular atrial fibrillation (NVAF). BACKGROUND Anticoagulants such as warfarin lower the risk of stroke in patients with NVAF. Ximelagatran is a novel, oral direct thrombin inhibitor with predictable pharmacokinetics and no known food or pharmacokinetic drug interactions. METHODS This was a 12-week, randomized, parallel-group, dose-guiding study of NVAF patients with at least one additional risk factor for stroke. The primary end point was the number of thromboembolic events and bleedings. Three groups received ximelagatran (n = 187) at 20, 40, or 60 mg twice daily, given in a double-blind fashion, without routine coagulation monitoring. In a fourth group, warfarin (n = 67) was managed and monitored according to normal routines, aiming for an International Normalized Ratio of 2.0 to 3.0. RESULTS A total of 254 patients received study drug. One ischemic stroke (nonfatal) and one transient ischemic attack (TIA) occurred in the ximelagatran group. Two TIAs occurred in the warfarin group. No major bleeds were observed in the ximelagatran group. One major bleed occurred in a warfarin-treated patient. The number of minor and multiple minor bleeds was low, but there was a slight increase by ximelagatran dose. The 60-mg dose resulted in the same number of bleeding events as that with warfarin. S-alanine aminotransferase was increased in eight patients (4.3%) taking ximelagatran, but normalized with continuous treatment or cessation of the drug. CONCLUSIONS Fixed oral doses of ximelagatran up to 60 mg twice daily were well tolerated, without the need for dose adjustment or coagulation monitoring.OBJECTIVESnWe sought to compare the tolerability and safety of three fixed doses of ximelagatran versus warfarin in patients with nonvalvular atrial fibrillation (NVAF).nnnBACKGROUNDnAnticoagulants such as warfarin lower the risk of stroke in patients with NVAF. Ximelagatran is a novel, oral direct thrombin inhibitor with predictable pharmacokinetics and no known food or pharmacokinetic drug interactions.nnnMETHODSnThis was a 12-week, randomized, parallel-group, dose-guiding study of NVAF patients with at least one additional risk factor for stroke. The primary end point was the number of thromboembolic events and bleedings. Three groups received ximelagatran (n = 187) at 20, 40, or 60 mg twice daily, given in a double-blind fashion, without routine coagulation monitoring. In a fourth group, warfarin (n = 67) was managed and monitored according to normal routines, aiming for an International Normalized Ratio of 2.0 to 3.0.nnnRESULTSnA total of 254 patients received study drug. One ischemic stroke (nonfatal) and one transient ischemic attack (TIA) occurred in the ximelagatran group. Two TIAs occurred in the warfarin group. No major bleeds were observed in the ximelagatran group. One major bleed occurred in a warfarin-treated patient. The number of minor and multiple minor bleeds was low, but there was a slight increase by ximelagatran dose. The 60-mg dose resulted in the same number of bleeding events as that with warfarin. S-alanine aminotransferase was increased in eight patients (4.3%) taking ximelagatran, but normalized with continuous treatment or cessation of the drug.nnnCONCLUSIONSnFixed oral doses of ximelagatran up to 60 mg twice daily were well tolerated, without the need for dose adjustment or coagulation monitoring.

Quality of Care and Mortality Among Patients With Stroke: A Nationwide Follow-up Study

Background:The relationship between process and outcome measures among patients with stroke is unclear. Objectives:To examine the association between quality of care and mortality among patients with stroke in a nationwide population-based follow-up study. Methods:Using data from The Danish National Indicator Project, a quality improvement initiative with participation of all Danish hospital departments caring for patients with stroke, we identified 29,573 patients hospitalized with stroke between January 13, 2003 and October 31, 2005. Quality of care was measured in terms of 7 specific criteria: early admission to a stroke unit, early initiation of antiplatelet or oral anticoagulant therapy, early examination with computed tomography/magnetic resonance imaging scan, and early assessment by a physiotherapist, an occupational therapist, and of nutritional risk. Data on 30- and 90-day mortality rates were obtained through the Danish Civil Registration System. Results:Six of 7 of these criteria were associated with lower 30- and 90-day mortality rates. Adjusted mortality rate ratios corrected for clustering by department ranged from 0.41 to 0.83. We found indication of an inverse dose-response relationship between the number of quality of care criteria met and mortality; the lowest mortality rate was found among patients whose care met all criteria compared with patients whose care failed to meet any criteria (ie, adjusted 30-day mortality rate ratios: 0.45, 95% confidence interval: 0.24–0.66). When analyses were stratified by age and sex, the dose-response relationship was found in all subgroups. Conclusions:Higher quality of care during the early phase of stroke was associated with substantially lower mortality rates.