Stroke Prevention with the Oral Direct Thrombin Inhibitor Ximelagatran Compared with Warfarin in Patients with Non-Valvular Atrial Fibrillation (SPORTIF III): Randomised Controlled Trial Executive Steering Committee on behalf of the SPORTIF III Investigators. Lancet 2003;362:1691– 8. Study Question: Is ximelagatran, an oral direct thrombin inhibitor, non-inferior to warfarin, within a margin of 2% per year, for prevention of strokes and systemic emboli in atrial fibrillation? Methods: 3,410 patients with persistent or paroxysmal atrial fibrillation (PAF) and one or more stroke risk factor were randomized to open label warfarin (target INR 2.0 –3.0) or ximelagatran 36 mg twice daily. Exclusion criteria included mitral stenosis and valvular heart surgery, recent CVA, bleeding risk, planned cardioversion or surgery, liver or renal disease, and treatment with a platelet inhibitor other than ASA at 100 mg/day or less within 10 days. Random- ization was balanced for use of ASA, and a history of CVA or TIA. Primary endpoint was stroke (ischemic and hemor- rhagic) or systemic embolism adjudicated by masked event assessment. Secondary endpoints were bleeding, treatment discontinuation, and single and combination of events in- cluding MI. Results: The mean age was 70 years, 70% were men, 20% were on ASA, 21% had onset less than 1 year, 8% had PAF, and 2 or more stroke risk factors were present in 70%. Over a mean of 17.44.1 mo. 96 patients had a primary event, 56 on warfarin and 40 on ximelagatran. The event rate by intention to treat was 2.3% per year with warfarin and 1.6% with ximelagatran, a 0.7% absolute and 29% rela- tive risk reduction, p0.10. All cause mortality was 3.2% in each group. The INR was below 2.0 in 25% of warfarin-treated patients at the time an ischemic CVA or TIA, or systemic embolus. Minor and major hemorrhages were lower with ximelagatran, 25.8% vs. 29.8% with warfarin, p0.007. Increases in ALT were more common with ximelagatran. Conclusions: In high-risk patients with atrial fibrillation, fixed dosing of oral ximelagatran was at least as effective as well controlled warfarin for prevention of stroke and sys- temic emboli. Perspective: Ximelagatran, an oral direct thrombin inhibi- tor, has been shown to be safe and effective in deep vein thrombosis and pulmonary emboli and atrial fibrillation. A simple fixed dose schedule, no drug interactions, and only periodic ALT laboratory monitoring are major advantages over warfarin. MR Anticoagulation Therapy for Stroke Prevention in Atrial Fibrillation. How Well Do Randomized Trials Translate Into Clinical Practice? Go AS, Hylek EM, Chang Y, et al. JAMA 2003;290:2685–92. Study Question: How safe and effective is prophylactic ther- apy with warfarin in patients with atrial fibrillation (AF) in routine clinical practice? Methods: The study cohort consisted of 11,526 patients with nonvalvular AF followed for a mean of 2.2 years in the Kaiser Permanente health care system. Data on warfarin use, thromboembolic events, and hemorrhagic events were obtained by reviewing prescriptions, international normal- ized ratios (INR), and medical records. Results: The mean age of the patients was 71 years, and 57% were males. Heart failure was present in 28%, hypertension in 50%, diabetes in 17%, and coronary artery disease in 28%. Warfarin was used in 57% of patients and was asso- ciated with a 51% reduction in the annual risk of thrombo- embolism, regardless of whether or not risk factors for stroke were present. The annual stroke rates in patients taking and not taking warfarin were 1.2% and 2%, respec- tively. Among patients treated with warfarin who had a stroke, the INR was 2.0 in 64%. Warfarin use was asso- ciated with a 2-fold increase in the risk of intracranial hemorrhage. There was a 31% reduction in annual all-cause mortality in patients taking warfarin. Conclusions: In routine clinical practice, the beneficial effects of prophylactic warfarin outweigh its risks in patients with AF. Perspective: The large-scale clinical trials that demonstrated the beneficial risk:benefit ratio of warfarin in patients with AF consisted of highly selected patients whose anticoagula- tion status was closely monitored. The present study is important because it demonstrates that the results of the anticoagulation trials apply to routine clinical practice. Of note is that 27% of INR’s were subtherapeutic during fol- low-up, reflecting the pharmacokinetic challenges that war- farin presents, and highlighting the potential advantages of a direct thrombin inhibitor such as Ximelagatran. FM Comparison of Recurrence Rates After Direct- Current Cardioversion for New-Onset Atrial Fibrillation in Patients Receiving Versus Those Not Receiving Rhythm-Control Drug Therapy Li H, Riedel R, Oldemeyer JB, Rovang K, Hee T. Am J Cardiol 2004;93:45– 8. Study Question: How effective is rhythm control therapy in preventing recurrences of atrial fibrillation (AF) after trans- thoracic cardioversion of new-onset, persistent AF? Methods: This was a retrospective analysis of 150 patients without a prior history of AF who underwent cardioversion of AF that had been present for 72 hours. Fifty patients were treated with a class IA, IC, or III antiarrhythmic drug at ACC CURRENT JOURNAL REVIEW Mar 2004 63 Arrhythmias Abstracts