Update from Cardiology Literature: Antithrombotic therapy in Atrial Fibrillation and CKD

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In 2015 I hope to blog on articles from non-renal journals that are of interest to nephrologists. First

up is cardiology and a topic that has been covered in previous RFN posts (here, here, here). The optimal

management of atrial fibrillation in patients with CKD is controversial as they are at both a higher

risk of stroke and higher risk of bleeding than the non-CKD population; this is particularly true of

patents on dialysis. Warfarin is well established in reducing the risk of stroke in patients with atrial

fibrillation but the trials excluded patients with a creatinine clearance of < 30ml/min. Thus we have

had to rely on, often contradictory, observational studies to guide us in this area.

A study in the Journal of the American College of Cardiology in December is the latest to

investigate the net clinical benefit (or harm) of antithrombotic therapy in these patients. It was a

retrospective cohort study using nationwide Danish registries to identify all patients discharged from

hospital with a diagnosis of non-valvular AF between 1997 to 2011. Out of the 154,259 patients

identified; 11,128 (7.2%) had non-end stage CKD and 1,728 (1.1%) were receiving dialysis. They used

the CHA2DS2-VASC score to stratify the patients into high and low/intermediate risk of stroke groups.

Briefly the score is calculated by adding one point for heart failure, hypertension, diabetes, vascular

disease, age 65-74 and female sex and 2 points for age over 75 and a previous stroke. A score of ≥ 2

is considered high risk.
They found that among high risk patients on dialysis, warfarin was associated with a significantly

lower risk of all-cause mortality (HR 0.85, CI 0.72-0.99) and there was a non-significant trend toward

a reduction in cardiovascular death and a composite end point of hospitalization or death from all

stroke/all bleeding. There was no benefit of warfarin in low-intermediate risk dialysis patients; indeed

there was a trend toward higher all-cause mortality (HR 1.36, CI 0.96-1.94).

Analysis of a sample of the non-end stage CKD patients found 19.1% were CKD stage 1-2, 20% were

CKD 3, 36.4% were CKD 4 and 24.5% were CKD 5. Warfarin was associated with significantly lower

risk of all-cause mortality in both high risk (HR 0.64) and low-intermediate risk groups (HR 0.62) in

patients with non-end stage CKD. One caveat, highlighted in the journal’s editorial, is that certain

components of the CHA2DS2-VASC score (diabetes, hypertension and heart failure) were identified

based on filled prescription data, meaning the frequency of these risk factors may have been

underestimated and therefore overestimating the number of patients classified as low-intermediate

risk. We should therefore interpret the mortality benefit for this group with caution.

The most recent NICE guidelines in the UK, published in June 2014, do not recommend aspirin as

monotherapy for the prevention of stroke in patients with AF. This study suggests the same should

apply to patients on dialysis as aspirin was not associated with a lower risk of any outcome.
Analysis of the newer anticoagulants such as Dabigatran, Rivaroxaban and Apixaban, were not

included in this study. They are contraindicated in patients with ESRD as they are cleared via the

kidneys and drugs levels can accumulate and precipitate bleeding though their use in this setting has

increased nonetheless. A study from the U.S. out this month in Circulation found that 5.9% of

anticoagulated patients with AF on dialysis are started on dabigatran or rivaroxaban and that these

drugs were associated with a higher risk of hospitalisation or death from bleeding compared to


Balancing the risks and benefits of anticoagulation in patients with AF and ESRD remains complex.

The current evidence suggests that warfarin remains the best anti-thrombotic available but it also

has a significant potential for harm and the decision of whether or not to start treatment needs to

be an individualized patient choice.

Authored by David Baird
Royal Infirmary of Edinburgh

1 comment

  1. Nice post David. It's intriguing that this is another Scandinavian study showing benefit of warfarin in advanced CKD. They appear to have less INR variability and likely a healthier cohort than US ESRD patients. http://www.ncbi.nlm.nih.gov/pubmed/24595776

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