Even With CKD, Warfarin Safely Cuts Events in AF After MI, Study Finds

March 04, 2014

STOCKHOLM, SWEDEN — Regardless of severity of renal dysfunction, the one-year risk of death, MI, or stroke went down significantly for patients hospitalized with acute MI and atrial fibrillation (AF) who were prescribed warfarin at discharge, compared with those not given warfarin, in an observational study based on the long-running SWEDEHEART registry[1].

The findings argue against withholding warfarin from post-MI patients with AF because they have advanced chronic kidney disease (CKD), a common caution throughout the world due to conflicting published data on warfarin's safety in that setting, write the authors, led by Dr Juan Jesús Carrero (Karolinska Institutet, Stockholm, Sweden), in the March 5, 2014 issue of the Journal of the American Medical Association. Moreover, they note, patients with CKD, especially advanced renal dysfunction, were usually excluded from the prospective trials that established warfarin for thromboembolic protection in patients with AF, as well as those supporting the new oral anticoagulants (NOACs).

An accompanying editorial[2] states that the study from Carrero et al "provides the best evidence to date suggesting that warfarin may be safe and effective in patients with advanced CKD, including those patients with an [estimated glomerular filtration rate] eGFR below 15 [mL/min/1.73 m2 ]."

Trial data has been inconclusive about the value of NOACs for AF when renal function is compromised, write Drs Wolfgang C Winkelmayer and Mintu P Turakhia (Stanford University School of Medicine, Palo Alto, CA), "However, case reports of severe bleeding episodes in patients with CKD are accumulating, and in more advanced CKD, novel oral anticoagulants are explicitly not indicated, contraindicated, or not recommended."

Carrero et al looked at 24 317 patients admitted with acute MI and AF surviving to discharge who were part of the prospective SWEDEHEART registry covering all hospitals in Sweden that provide acute cardiac care. Of those discharged, 21.8% had been prescribed warfarin on leaving the hospital and 51.7% had CKD, defined as an eGFR <60 mL/min/1.73m2.

In multivariate analysis, those who went on warfarin, compared with the rest, showed a significantly reduced hazard ratio for the composite of death, MI readmission, or ischemic stroke at one year, independently of eGFR.

Hazard Ratio (HR, 95% CI) at One Year for Death, MI, or Ischemic Stroke in Patients With Recent MI and AF, by Degree of Renal Dysfunction (p for trend=0.81)

Groups by Renal Function HR (95% CI)
All patients 0.73 (0.68–0.78)
eGFR >60 0.73 (0.65–0.81)
eGFR >30 to 60 0.73 (0.66–0.80)
eGFR >15 to 30 0.84 (0.70–1.02)
eGFR <15 0.57 (0.37–0.86)

eGFR in mL/min/1.73m2
Adjusted for age, sex, center, eGFR, preexisting CV comorbidities and cancer, syndrome at presentation, revascularization at index hospitalization, and discharge CV medication

The adjusted risk of bleeding, including major bleeding, was not significantly increased in warfarin recipients (HR 1.02, 95% CI 0.86–1.20) overall or at any of the eGFR strata from normal to <15 mL/min/1.73m2.

According to the editorial, time in the INR therapeutic range (TTR) is the best predictor of warfarin safety and effectiveness, and "Sweden has better quality of INR control than any other country, as evidenced both in this study (TTR, 75%) and in the multicountry RE-LY clinical trial of warfarin vs dabigatran (TTR, 77%)." In contrast, the TTR in the US was only 66% in RE-LY and is lower in clinical practice.

The current data, write Winkelmayer and Turakhia, "support the use and continuation of warfarin therapy among patients with CKD with excellent INR control."

Carrero reports receiving grant funding from the Centre for Gender Medicine at Karolinska Institutet, the Swedish Medical Research Council, and the Westman Foundation; disclosures for the other authors are listed in the paper. Winkelmayer reports serving as an advisor or consultant to Acumen, Amgen, GlaxoSmithKline, Keryx, Medgenics, Medtronic, and Mitsubishi Tanabe, and serving as coeditor for the American Journal of Kidney Diseases; he currently serves as an associate editor for JAMA . Turakhia reports serving as an advisor or consultant to Medtronic, St Jude Medical, and Precision Health Economics and receiving grant support from Medtronic, Gilead Sciences, and iRhythm.

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