A comparison of methods for estimating glomerular filtration rate for a population in Hawai'i with non-valvular atrial fibrillation.
Warfarin is the primary treatment for those with atrial fibrillation at increased risk for stroke. The Randomized Evaluation of Long-Term Anticoagulation Therapy (RELY) trial demonstrated that dabigatran, a direct thrombin inhibitor, was associated with lower rates of systemic embolism compared to warfarin.1 Although individuals with a creatinine clearance of less than 30 mL/min were excluded from the trial, the FDA approved the use of dabigatran for those with creatinine clearances as low as 15 mL/min, with a lower dose of dabigatran recommended for individuals with creatinine clearances below 30 mL/min. This study calculated Glomerular Filtration Rates (GFR) via three existing formulas with varying levels of accuracy (ie, the Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) to evaluate how patient eligibility for the RELY trial may have varied depending upon the formula used. A retrospective study was performed based on a chart review conducted at a private cardiologist's office in Honolulu, Hawai'i using patients with non-valvular atrial fibrillation. Patients included were those with a BUN/Creatinine assessment within 12 months of the chart review and a CHADS2 (Congestive Heart Disease, hypertension, age greater than 75, diabetes mellitus, and stroke or transient ischemic attack) score of 1 or greater. Of 376 subjects assessed, 64 subjects who failed to meet criteria for the RELY trial when using the Cockcroft-Gault formula (ie, GFR estimates were lower than 30 mL/min) met eligibility criteria when the MDRD formula was used (ie, GFR estimates exceeded 30 mL/min). Subgroup analysis of the 64 subjects revealed that subjects were 89-years-old on average, predominantly female (76.5%), and mostly Japanese (62.5%). Nearly one in five individuals (17%) in the studied population would have received a lower dose of dabigatran if the Cockcroft-Gaunt formula was used for estimating GFRs. The authors recommend caution while dosing dabigatran in the Asian population, as the estimates of kidney functioning vary substantially depending on the formula used to estimate GFR, which may in turn lead in some cases of inadequate dosing of dabigatran.
Department of Medicine, John A. Burns School of Medicine, University of Hawai'i, Honolulu, HI.
Corey J
CJ
Lum
Steven
S
Azuma
D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000627:therapeutic use; D001120:Arginine / Q000031:analogs & derivatives; D044466:Asian People; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000627:therapeutic use; D000069604:Dabigatran; D005260:Female; D005919:Glomerular Filtration Rate; D006254:Hawaii; D006801:Humans; D008297:Male; D009025:Morpholines / Q000627:therapeutic use; D010875:Pipecolic Acids / Q000627:therapeutic use; D012189:Retrospective Studies; D000069552:Rivaroxaban; D013449:Sulfonamides; D013876:Thiophenes / Q000627:therapeutic use; D014859:Warfarin / Q000627:therapeutic use; D015091:beta-Alanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000925:Anticoagulants; D001562:Benzimidazoles; D009025:Morpholines; D010875:Pipecolic Acids; D013449:Sulfonamides; D013876:Thiophenes; D015091:beta-Alanine; D014859:Warfarin; D001120:Arginine; D000069552:Rivaroxaban; D000069604:Dabigatran; C031942:argatroban