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Renal impairment tied to higher stroke risk in anticoagulated AF patients

NEW YORK (Reuters Health) – Anticoagulated patients with atrial fibrillation (AF) and impaired renal function are at increased risk of stroke and major bleeding compared to those with better kidney function, according to a new post-hoc analysis of clinical trial results.

“Patients who have atrial fibrillation and impaired renal function are a high-risk group, and of course they need very careful assessment and addressing of cardiovascular risk factors as much as possible,” Dr. Gregory Y. H. Lip of the University of Birmingham Centre for Cardiovascular Services in the UK told Reuters Health.

Up to 27% of patients on long-term hemodialysis have AF, Dr. Lip and his team note in the European Heart Journal online August 21, and chronic kidney disease (CKD) can lead to both hyper- and hypocoagulability.

To better understand how kidney function influences stroke and bleeding risk in patients with AF receiving anticoagulant therapy, and also determine whether including CKD in stroke risk stratification scoring might improve predictive value, Dr. Lip and his colleagues analyzed data from AMADEUS, a trial comparing idraparinux to warfarin treatment for preventing thromboembolism in more than 4,500 AF patients.

During an average of 325 days of follow-up, 45 strokes or non-central-nervous-system systemic embolisms (SE) occurred, along with 103 major bleeding events. The annual stroke/SE risk was 0.6% for patients with CrCl greater than 90 mL/min; 0.8% for patients with CrCl of 60-90 mL/min; and 2.2% for patients with CrCl below 60 mL/min.

Once the researchers adjusted for other stroke risk factors, they found patients with CrCl below 60 mL/min had more than a two-fold increase in stroke risk compared with those with CrCl of 60 mL/min or higher. The association was particularly strong among patients at lower risk for stroke based on CHA2DS2VASc score; the risk was increased more than eight-fold for patients with a score of 1-2 on this scale who had CrCl below 60 mL/min compared with those with better kidney function.

However, adding CrCl below 60 mL/min did not improve c-indexes with CHA2DS2VASc or CHADS2. “This is perhaps unsurprising given that CKD is commonly associated with the individual risk factors making up the components of the CHA2DS2VASc or CHADS2 scores,” Dr. Lip and his team write.

Patients with CrCl below 60 mL/min were also at 58% higher risk of a major bleeding event compared to those with better kidney function.

The risk of stroke associated with impaired renal function could be different for patients with AF who are not receiving anticoagulant treatment, the researchers note. “Further studies are required to establish whether CrCl-adjusted risk scores would have a similar performance in ‘real-world’ unselected populations, including non-anticoagulant AF populations,” they add.

Based on the findings, Dr. Lip told Reuters Health, renal function should be included in the assessment of all patients with atrial fibrillation, especially in the context of newer anticoagulants, because their pharmacologic effects are affected by kidney function.


Eur Heart J 2013.