Pharmacokinetic and clinical implications of dabigatran use in severe renal impairment for stroke prevention in nonvalvular atrial fibrillation

OBJECTIVE: To review the literature regarding the pharmacokinetic (PK) and clinical implications of the use of dabigatran in severe renal impairment for stroke prevention in nonvalvular atrial fibrillation (AF). DATA SOURCES: Searches of MEDLINE (2000-April 2012) and the Cochrane Database (2000-April 2012) were conducted. Key search terms included dabigatran, renal impairment, renal failure, and renal dysfunction. Additional limits included articles written in English and those involving human subjects. Bibliographic reviews were conducted to identify other pertinent data. STUDY SELECTION AND DATA EXTRACTION: Primary data were considered eligible for inclusion if they were from studies that evaluated the PKs of dabigatran in renal impairment or the effect of renal impairment on the risk for major bleeding with dabigatran. DATA SYNTHESIS: Dabigatran is an oral direct thrombin inhibitor indicated for the prevention of stroke and systemic thromboembolism in patients with nonvalvular AF, at a dose of 150 mg twice daily. Renal elimination is responsible for approximately 80% of dabigatran's clearance; thus, dose adjustment is required for patients with severe renal impairment. The approved dosing regimen for patients with creatinine clearance 15-30 mL/min (75 mg twice daily) was derived from PK modeling studies, limiting its applicability to the clinical setting. CONCLUSIONS: At this time, there is limited evidence to support safety or efficacy outcomes with the use of dabigatran for stroke prevention in patients with severe renal impairment and nonvalvular AF. Postmarketing data and large clinical trials are needed to determine the role of dabigatran in this population.