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