Warfarin May Be Good Even With Kidney Disease

Among patients with atrial fibrillation and a recent heart attack, warfarin use was associated with improved outcomes -- without excess bleeding -- regardless of the level of kidney function, a Swedish study showed.

Through 1 year after the myocardial infarction (MI), patients who were prescribed warfarin at discharge had a significantly lower rate of death, readmission due to MI, or ischemic stroke, a finding consistent for those with normal renal function, moderate-to-severe chronic kidney disease, and end-stage renal disease, according to Juan Jesús Carrero, PhD, of the Karolinska Institute in Stockholm, and colleagues.

The findings were similar when bleeding was included in the endpoint, they reported in the March 5 issue of the Journal of the American Medical Association.

Because of the observational nature of the study, however, the results "do not provide conclusive guidance regarding anticoagulant therapy in patients with atrial fibrillation and chronic kidney disease," Carrero and colleagues wrote. "Nevertheless, clear ethical concerns may not allow such trials."

Questions remain about the effects of warfarin in patients with both advanced chronic kidney disease and atrial fibrillation, who have a greater risk for stroke compared with patients with atrial fibrillation alone. Anticoagulation trials have generally excluded patients with kidney disease, but observational studies in this patient population have provided mixed results, with some showing harms from anticoagulation and some showing no harm.

To explore the issue, Carrero and colleagues looked at data from the prospective SWEDEHEART registry, which collects information from all Swedish hospitals that provide acute cardiac care. The analysis included 24,317 patients who survived to discharge following an acute MI and had atrial fibrillation from 2003 to 2010.

Overall, 21.8% received a warfarin prescription at discharge. About half (48%) had normal renal function (estimated glomerular filtration rate above 60 mL/min/1.73 m²), 42% had moderate dysfunction (eGFR 30 to 60 mL/min/1.73 m²), 8% had severe dysfunction (eGFR 15 to 30 mL/min/1.73 m²), and 2% had end-stage renal disease.

The 1-year rate of death, readmission due to MI, or ischemic stroke was higher in worsening categories of renal dysfunction, but warfarin use was associated with a reduced risk regardless of renal function.

For those with normal renal function, for example, the rate of the composite endpoint (per 100 person-years) was 28.0 in the warfarin group and 36.1 in the rest of the patients (adjusted hazard ratio 0.73, 95% CI 0.65-0.81). Similar differences were seen in the patients with end-stage renal disease (83.2 versus 128.3, HR 0.57, 95% CI 0.37-0.86) and in those with less severe dysfunction.

In an accompanying editorial, Wolfgang Winkelmayer, MD, ScD, and Mintu Turakhia, MD, of Stanford University in Stanford, Calif., pointed out some limitations of the analysis, including the possibility of confounding by unidentified factors, the inability for an observational study to establish cause-and-effect, and the uncertain generalizability of the findings beyond patients with a recent MI.

In addition, they noted, Sweden has been shown to have the best international normalized ratio (INR) control for patients with warfarin compared with other countries.

"Kidney function has been shown to directly influence warfarin responsiveness, time in therapeutic range, and time above INR therapeutic range," Winkelmayer and Turakhia wrote. "Therefore, unless the excellent quality of INR control achieved by the Swedish Health Care System can be replicated, the benefit of warfarin is likely to be markedly attenuated and possibly could cause harm."

Those caveats aside, however, the study "provides the best evidence to date that vitamin K antagonists are associated with improved clinical outcomes and no significant increased risk of bleeding in patients with myocardial infarction and atrial fibrillation with advanced chronic kidney disease," they wrote. "These data support the use and continuation of warfarin therapy among patients with chronic kidney disease with excellent INR control."

Source: www.medpagetoday.com