Severe Renal Impairment and Stroke Prevention in Atrial Fibrillation: Implications for Thromboprophylaxis and Bleeding Risk

Perspective:

The following are 10 points to remember from this review of stroke prevention in patients with atrial fibrillation (AF) and end-stage renal disease (ESRD):

1. The prevalence of AF in patients with ESRD is reported to be 7-27%, or 10-20 times higher than in the general population.

2. The high prevalence of AF in ESRD is related to ischemic heart disease, hypertrophy, hypertension, unstable electrolyte levels, autonomic activation, and modulation of the renin-angiotensin system.

3. Compared to other patients with AF, patients with ESRD and AF have a 5- to 10-fold higher risk of stroke due to coagulation abnormalities, platelet dysfunction, and frequent multiple comorbidities such as hypertension and diabetes.

4. ESRD is an independent risk factor for major hemorrhage during treatment with warfarin, at least partly because of functional platelet abnormalities and uremic toxins.

5. Vitamin K antagonism by warfarin can be deleterious in ESRD by reducing the function of endogenous vitamin K-dependent inhibitors of calcification.

6. The international normalized ratio (INR) often is unstable in ESRD and the time-in-therapeutic-range (INR 2-3) has been <50% in observational studies.

7. ESRD is not included in stroke risk-stratification schema such as the CHADS2 or CHA2DS2-VASc score.

8. ESRD is included as a risk factor in three published bleeding risk-stratification schema.

9. There have been no clinical trials evaluating the risk-benefit ratio of warfarin for stroke prevention in ESRD, but given the high risk of stroke, well-controlled anticoagulation with warfarin probably is the best strategy for stroke prevention in ESRD.

10. The safety and efficacy of other anticoagulants that can be used in ESRD, such as betrixaban (a factor X-A inhibitor), remain to be determined.

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Hypertension

Keywords: Vitamin K, Myocardial Ischemia, Stroke, Kidney Failure, Chronic, Factor X, Renin-Angiotensin System, Pyridines, Blood Platelets, Benzamides, Hypertrophy, Hypertension, Diabetes Mellitus


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