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Warfarin reduced CV event risk in patients with CKD, MI, AF

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Warfarin reduced the 1-year risk for death, MI and ischemic stroke in patients with concomitant chronic kidney disease, acute MI and atrial fibrillation in a recent study.

Moreover, this association was not affected by the severity of kidney disease.

The observational, prospective, multicenter cohort study evaluated 24,317 patients enrolled in the SWEDEHEART registry after presenting with suspected ACS at one of 72 Swedish hospitals between 2003 and 2010. Patients enrolled in the current study were diagnosed with acute MI and AF and had known serum creatinine levels.

Renal function was categorized as normal/chronic kidney disease (CKD) stage 1 or 2 (estimated glomerular filtration rate [eGFR] >60 mL/min/1.73 m²), moderate dysfunction/stage 3 (eGFR of 30-60 mL/min/1.73 m²), severe dysfunction/stage 4 (eGFR of 15-30 mL/min/1.73 m²) and end-stage renal disease/stage 5 (≤eGFR of 15 mL/min/1.73 m²).

The primary outcomes included a composite of death, MI- or ischemic stroke-related readmission; readmission due to bleeding; or the aggregate of these two outcomes within 1 year of discharge.

Of the 24,317 patients, 21.8% began a warfarin (Coumadin, Bristol Myers-Squibb) regimen at discharge. Among warfarin recipients, 41.7% had CKD stage 3, 8.1% had stage 4 and 2% had stage 5.

Researchers observed an association between warfarin use and reduced risk of the composite outcome in each kidney disease category vs. nonrecipients. Event rates for the composite outcome were 28 cases per 100 person-years among warfarin recipients vs. 36.1 for nonrecipients (adjusted HR=0.73; 95% CI, 0.65-0.81) in patients with normal renal function; 48.5 per 100 person-years vs. 63.8 (HR=0.73; 95% CI, 0.66-0.8) for moderate dysfunction; 84.3 per 100 person-years vs. 110.1 (HR=0.84, 95% CI, 0.7-1.02) for severe dysfunction; and 83.2 per 100 person-years vs. 128.3 (HR=0.57; 95% CI, 0.37-0.86) for end-stage renal disease.

Bleeding risk also was not significantly higher and risk for mortality was significantly lower among warfarin recipients, regardless of kidney disease severity. Multivariable adjustment did not significantly alter the associations between warfarin and treatment outcomes.

In an accompanying editorial, Wolfgang C. Winkelmayer, MD, MPH, ScD, division of nephrology, and Mintu P. Turakhia, MD, MAS, division of cardiovascular medicine at Stanford University School of Medicine, wrote that further study is needed, but these findings provide the most conclusive information to date about the safety of warfarin in CKD patients.

“Although previous analyses have demonstrated efficacy of oral anticoagulation using warfarin in patients with moderate CKD … the present observational study provides the best evidence to date suggesting that warfarin may be safe and effective in patients with advanced CKD, including those patients with an eGFR below 15,” they wrote.

For more information:

Carrero JJ. JAMA. 2014;311:919-928.

Winkelmayer WC. JAMA. 2014;311:913-915.

Disclosure: See the full study for a list of relevant financial disclosures.