The Efficacy of Dabigatran versus Warfarin for Stroke Prevention in Patients With Atrial Fibrillation: Systematic Review Karim Bouferrache Pacific University School of Physician Assistant Studies, Hillsboro, OR USA Results The PETRO Study by Ezekowitz (2007) randomized subjects into a 3 X 3 factorial distribution to receive either a combination of dabigatran (50 mg, 150 mg or 300 mg bid) and aspirin (0, 81 mg or 325 mg daily) or to receive adjusted-dose warfarin alone. While the dose of dabigatran was blinded, both warfarin and aspirin were open-label. Therapy lasted for 12 weeks. Overall there were only two thromboembolic events during the study, both of which occurred in patients taking dabigatran 50 mg twice daily (1.96%), one with the use of 81 mg of aspirin and one with no aspirin. One patient had a peripheral embolism to the toe and the other patient had a stroke and a renal infarction. However, the patients taking 300 mg BID daily dabigatran along with aspirin had a major hemorrhage rate of 6.3% (4 of 64). The rate was statistically different compared with the group treated with dabigatran 300 mg twice daily without aspirin (0 of 105, p <0.02). The RE-LY study by Connolly et al. (2009) enrolled 18,113 patients from 44 countries. Patients were randomized to receive either a blinded dose of dabigatran (110 or 150 mg twice daily) or open-label warfarin, with a target value of Patients were followed for a median period of two years. Dabigatran 110 mg twice daily was equivalent to warfarin for thromboembolic prophylaxis. With an event rate of 1.53% per year in this group, versus 1.69% per year in the warfarin group, the relative risk with 110 mg dabigatran therapy was 0.91 (95% CI, 0.74 to 1.11; p=.34), thus meeting the pre- specified non-inferiority criteria. Among patients taking 150 mg of dabigatran, the prophylactic effect surpassed non-inferiority, and demonstrated superiority to warfarin; the rate was 1.11% per year, versus 1.69% for the warfarin group, with a relative risk of 0.66 with this therapy (95% CI, 0.53 to 0.82; p <.001). Discussion The Grading of Recommendations Assessment Development and Evaluation (Grade) was used in this paper to evaluate the quality of evidence and strength of recommendations provided in this review. The trials chosen in this review, the PETRO, Ezekowitz et al. (2007) and RE-LY, Connolly et al. (2009) were randomized control trials, which are at a “high” type of evidence according to the GRADE criteria. The RE-LY study had stroke and systemic embolism as primary outcomes. However, it appears that the PETRO study had these outcomes as tertiary. But the outcomes were wholly consistent and the RE-LY study even modified their dosing based on the PETRO study giving further indicia of confidence in their early findings. This decision not to downgrade the evidence leaves a GRADE score of high for the combined outcomes Introduction Atrial fibrillation (AF) is the most common cardiac arrhythmia and a risk factor for stroke and systemic embolism. The patient prevalence is 2.3 million in the United States and likely to increase 2.5-fold during the next 50 years. Consequently, the stroke rate and systemic embolism rates due to AF will also increase. It has been established that warfarin is an effective drug to prevent stroke and systemic embolism in patients with AF, but this drug is cumbersome to use because of their delayed onset of action, differences in effects on the coagulation cascade, and multiple interactions with food and drugs that necessitate frequent laboratory monitoring. Dabigatran etexilate, recently approved by the FDA, is an oral direct thrombin inhibitor that enables the conversion of fibrinogen into fibrin, thus, prevent the development of a thrombus. This paper comprehensively review research that compares warfarin and dabigatran in reducing the risk of stroke and systemic embolism in patients with AF. Purpose This paper focuses on the current literature on preventive therapy for stroke and systemic embolism in patients with atrial fibrillation. It is a systematic review of the literature that examines the efficacy of dabigatran compared to warfarin therapy in patients with AF to prevent stroke and systemic embolism. This paper uses the Grading of Recommendations Assessment Development and Evaluation (GRADE) criteria to evaluate the strength of evidence for this research Method An extensive review of the literature search was performed using the following database: Web of Science, MEDLINE and CINHAL. These databases were accessed through the Pacific University Library system. The following keywords were searched individually and in combination: “warfarin”, “atrial fibrillation”, “nonvalvular” and “dabigatran”. The search was limited to human subjects, the English language and full text articles. The initial results included 4 articles of which duplicates, descriptive reviews and letters to editors were excluded. Only randomized, controlled trials were reviewed. This resulted in two studies to review and include in the final analysis. Conclusion In conclusion, dabigatran is the first oral anticoagulant approved by the FDA in the last 50 years albeit in one dosage. It showed as a safer and superior alternative to warfarin for stroke prevention in patients with atrial fibrillation. For patients and clinicians having difficulties keeping INR at range (57% average)as well as newly diagnosed patients with atrial fibrillation, we recommend dabigatran as best initial anticoagulation therapy for stoke and systemic embolism prevention ComparisonOutcomeQuantity and type of evidence Findings Starting grade Decrease GRADEIncrease GRADEGrade of Evidence for Outcome Overall GRADE of Evidence Study Quality Consistency Directness Precision Publication Bias Large Magnitude Dose-Response Confounders Dabigatran Vs Warfarin in patients with atrial fibrillation Stroke prevention 2 RCTDecreased stroke events High Preventing systemic embolism 2 RCTDecreased systemic embolism High