Table 2.

Subgroup analysis of a single randomized clinical trial of warfarin for stroke prevention in CKD not on dialysis with atrial fibrillation

Study CharacteristicsaPublication and SponsorIntervention and ControlCKD Stage (n/N, %)bOutcomesResultsaConclusion
Post hoc CKD subgroup analysis unblinded RCT of Stroke Prevention in Atrial Fibrillation trials 1993–1997 United States and Canada, 1.3 mean yr follow-up4Robert G. Hart, CJASN 2011 National Institute of Neurologic Disorders and StrokeDose-adjusted warfarin, INR 2–3 (mean achieved 2.4). Fixed, low-dose warfarin (1–3 mg/d, mean INR achieved 1.3) plus 325 mg aspirin/d.Stage 3 CrCl<60 ml/min 516 of 1044 (49%) (267 dose-adjusted warfarin and 249 fixed low-dose warfarin). Baseline creatinine >3 mg/dl excluded.Primary: Ischemic stroke and or systemic thromboembolism. Secondary: Relevant bleedingcThe 2-yr event rate with dose-adjusted warfarin was 6 of 267 and low-dose warfarin and ASA was 23 of 249. The 2-yr event rate for dose-adjusted warfarin was 5 of 267 and low-dose warfarin and ASA was 6 of 249.76% RR (95% CI, 42 to 90) of ischemic stroke and systemic thrombo-embolism with dose-adjusted warfarin over fixed low-dose warfarin and ASA. Too few events to compare relevant bleeding. Dose-adjusted warfarin offers benefit over fixed low-dose warfarin and ASA 325 mg/d in reduction of ischemic stroke and systemic embolism in individuals with CKD stage 3.
  • RCT, randomized controlled trial; CJASN, Clinical Journal of the American Society of Nephrology; INR, international normalized ratio; CrCl, creatinine clearance; ASA, aspirin; RR, risk reduction; 95% CI, 95% confidence interval.

  • a Intention-to-treat analyses.

  • b Stage 4/5 (CrCl<30 ml/min), 27 of 1044 (3%) were removed from analyses. There are no randomized, controlled trials or subgroup analyses in stage 4/5 CKD.

  • c Relevant bleeding defined as occurring 14 d of receiving warfarin without a predictable precipitating cause (e.g., major trauma, cardiac surgery).