Threshold for anticoagulant therapy the same for AF patients with or without renal failure

Friberg L, Benson L, Lip GY
Eur Heart J. 2014 Apr 9

Background

Finding the optimal treatment of patients who have both atrial fibrillation (AF) and renal failure may be complicated, because both conditions confer an increased risk of ischaemic stroke. Furthermore, patients with renal failure are at increased risk of bleeding, while patients with AF are often treated with anticoagulants, which increase the risk of bleeding [1-3].
AF patients with renal failure have a higher risk of ischaemic stroke than patients without impaired renal function [4,5]. It has therefore been proposed that renal failure be added to the stroke risk stratification schemes for AF (CHADS₂ and CHA₂DS₂-VASc), to lower the threshold for anticoagulant treatment for these patients. Others have noted that since renal failure is a risk factor for bleeding complications, the threshold for initiation of anticoagulation should be raised especially if a patient is on haemodialysis.
No randomised trial to date has addressed the risk-benefit ratio of anticoagulant therapy in patients with both AF and renal failure. Using the Swedish health registers, this study investigated the risk of ischaemic stroke and bleeding in this patient group, in relation to the presence or absence of oral anticoagulant therapy. It further aimed to determine whether the threshold for anticoagulant treatment should be different for these patients, than for other AF patients. Data of 283969 patients diagnosed with AF were used for this study, of whom 13435 (4.6%) had a history of renal failure.

Main results

• Ischaemic stroke was more frequent in patients with renal failure (3.9% vs. 2.9% annually). After adjustment for cofactors, no excess risk related to renal failure remained for ischaemic stroke (HR: 1.02, 95%CI: 0.95-1.10). A modest association was observed for the less stringent endpoint ‘thrombo-embolism’, which included transient ischaemic attacks (TIA) and unspecified strokes, with renal failure (HR: 1.12, 95%CI: 1.07-1.18).
• Adding 1 or 2 points for renal failure to the CHADS₂ and CHA₂DS₂-VASc scores did not improve predictive value.
• Intracranial bleedings occurred more often in AF patients with renal failure (0.8% vs. 0.5% annually). The more inclusive secondary endpoint of ‘any bleeding’ was more common in AF patients with renal failure (9.8% vs. 4.1%). Adjustment for cofactors showed that renal failure was an independent risk factor for intracranial bleeding (HR: 1.27, 95%CI: 1.09-1.49) and the ‘any bleeding’ endpoint (HR: 1.56, 95%CI: 1.48-1.63).
• Adding ‘death from any cause’ to the combined endpoint ‘stroke’ yielded a significantly increased risk for patients with renal failure, after correction for comorbidities (HR: 1.60, 95%CI: 1.56-1.64).
• Irrespective of renal failure, patients who used warfarin at baseline had a lower risk of ischaemic stroke, thrombo-embolism and death than patients not on warfarin (HR: 0.69 in patients with renal failure, HR: 0.70 in patients without renal failure, P(interaction)= 0.865).
• The increased risk of bleeding associated with warfarin was similar for patient with and without renal failure (10% and 15% respectively, P(interaction)=0.368). A non-significantly higher risk of intracranial bleeding was seen for renal failure patients (HR: 1.56 vs. HR: 1.29).
• Even patients with high risk of bleeding (HAS-BLED score >3) seemed to benefit from warfarin (HR for ischaemic stroke or intracranial bleeding events: 0.82, 95%CI: 0.70-0.98 and HR for composite of ischaemic stroke, intracranial bleeding or death: 0.74, 95%CI: 0.70-0.79).

Conclusion

The current data confirm that renal failure is an independent risk factor for bleeding in AF patients, and thus supports inclusion of renal failure as a risk factor in the HAS-BLED score. Importantly, most AF patients with renal impairment still appear to benefit from warfarin treatment. Renal failure patients on warfarin had more favourable net outcome than those who did not receive warfarin. The net clinical benefit of anticoagulant therapy should always be carefully assessed for the individual patient with AF and renal failure.
Overall, patients with both AF and renal failure will probably benefit most from getting the same treatment as recommended for AF patients without renal impairment, thus with an unaltered threshold for anticoagulant treatment.

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References

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