Tidings from the Citadel: Warfarin in Dialysis

Warfarin Use and the Risk for Stroke and Bleeding in Patients With Atrial Fibrillation Undergoing Dialysis – Mitesh Shah et al. Circulation. 2014;129:1196-1203.

A retrospective cohort study

Population based cohort of patients > 65 years who were admitted in Canada – Quebec and Ontario with a primary or secondary diagnosis of atrial fibrillation. Used ICD-9/10 codes to determine diagnosis and complications such as bleeding and stroke complications. Drug prescriptions were identified by database in Canada where patients > 65 have prescription benefit. Warfarin use was identified by a filled prescription within 30-days of AF diagnosis

Patients
626 dialysis patients and 204,210 nondialysis patients. Did not separate by stages of CKD, but rather HD or non-HD. Dialysis patients were younger, male, CHF, HTN, DM, CAD, and bleeding history.

Dialysis vs Non-Dialysis: CHADS2 >/= 2: 72% versus 55% (indication for anti-coagulation); HAS-BLED >/=3: 85% versus 25%. Similar rates of warfarin prescription (46% vs 51%)

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Stroke
In non-dialysis patients, warfarin users had a lower incidence of stroke (2.19 vs 2.51/100 person-years)

In dialysis patients, stroke incidence was similar for warfarin and non-warfarin users: 3.37 versus 2.91/100 person-years.

After adjusting for confounders – warfarin use had a HR of 1.14 in diaylsis patients. While in non-dialysis patients had a HR 0.87 with warfarin use.

Bleeding
After adjusting for confounders, warfarin use, was associated with a 44% higher risk for bleeding event in dialysis patients and 19% higher risk in nondialysis patients.

 

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Flea Bytes: Asymptomatic Bacteriuria

  • Definition of Bacteriuria
    • Women: 2 samples of same organism CFU >10^5
    • Men: 1 clean catch sample  CFU >10^5
    • Catheterized patients: CFU >10^2
  • Who gets treated? According to the IDSA: 
    • Pregnant women
    • Patients undergoing urologic procedures
    • No recommendation is made for organ transplant recipients by IDSA
      • However asymptomatic bacteriuria within 3 months of transplant is associated with rejection so these are usually treated
      • A 2011 trial found no difference in outcomes treating vs. not treating bacteriuria in transplant patients
    • Pyuria, elderly, and diabetes are NOT indications to treat

Flea Bytes: Apixaban in Severe Renal Failure

In 2014, the FDA approved the label change for apixaban to include dosing recommendations for patients with severe renal failure or on hemodialysis. Previously the labeling stated that there was no data to inform the use of apixaban in patients with creatinine clearance < 15 or on dialysis. The data with which this change was made was sparse.

We know that 27% of the drug is eliminated unchanged by the kidneys.

There was a small single dose pharmacokinetic study of 8 patients on dialysis. Dialysis removed 14% of the drug. This study found a drug exposure area under the curve increase of 36%. Importantly, there was no data collected to inform the clinician the effects of repeated doses of the drugs and the possibility of drug accumulation.

I would not recommend apixaban as a first line anticoagulant in ESRD, but in cases where options are limited and risks and benefits are discussed with the patient – it may be reasonable to use based on the above information.