Anticoagulants Tied With Stroke, Hemorrhage in CKD

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Study questions the efficacy and safety of prescribing anticoagulants to older patients with atrial fibrillation and nondialysis chronic kidney disease.
Study questions the efficacy and safety of prescribing anticoagulants to older patients with atrial fibrillation and nondialysis chronic kidney disease.

Older patients with chronic kidney disease (CKD) who take anticoagulants for coexisting atrial fibrillation appear to have greater risks for ischemic stroke and bleeding, according to a new study.

Since previous studies yielded mixed findings on risks associated with anticoagulants in this population, A. John Camm, MD, professor of clinical cardiology at the Molecular and Clinical Sciences Research Institute in St George's University of London in the UK, and colleagues examined The Royal College of General Practitioners Research and Surveillance Centre database, including 2.7 million real-world patients from England and Wales. The investigators identified 6977 patients with CKD (estimated glomerular filtration rate less than 50 mL/min/1.73m2, not on dialysis) and newly diagnosed atrial fibrillation older than age 65. Of these, 2434 received a new prescription for anticoagulants within 60 days of diagnosis, including vitamin K antagonists (71.7%), rivaroxaban (12.7%), apixaban (10.8%), dabigatran (2.8%), unfractionated or low molecular weight heparin (1.8%), and edoxaban (0.17%). Drug-exposed patients were then matched to unexposed patients by propensity score and followed for a median 506 days.

According to results published in the BMJ, anticoagulant recipients fared worse than nonusers. Ischemic stroke developed in 4.6 vs 1.5 cases per 100 persons per year. In addition, cerebral or gastrointestinal hemorrhage occurred in 1.2 vs 0.4 cases per 100 persons per year. Anticoagulant recipients had 2.6- and 2.4-fold greater risks for ischemic stroke and hemorrhage, respectively. Yet they experienced 28% lower risks for dying compared with unexposed patients.

“Careful consideration should be given before starting anticoagulants in older people with chronic kidney disease who develop atrial fibrillation,” Dr Camm and his colleagues stated. The investigators noted that clinical practice guidelines in this critical area are lacking.

"As we found a paradoxical reduced mortality rate alongside increased rates of stroke and major bleeding, this is clearly a very complex area,” first author Shankar Kumar, MD, of the UCL Centre for Medical Imaging, stated in a news release. “We strongly call for randomised controlled studies to test the clinical value and safety of anticoagulant drug therapy for people with both atrial fibrillation and chronic kidney disease."

The findings of increased bleeding corroborate previous research, but the association between anticoagulants and ischemic stroke is new. The investigators suggested that vascular calcification and anticoagulant-related renal effects might be contributing to ischemic stroke in older patients.

References

Kumar S, de Lusignan S, McGovern A, et al. Ischaemic stroke, haemorrhage, and mortality in older patients with chronic kidney disease newly started on anticoagulation for atrial fibrillation: a population based study from UK primary care. BMJ 2018;360:k342. doi:10.1136/bmj.k342

Blood thinners may raise stroke risk in over-65s with kidney disease. [news release] University College London, February 14, 2018.

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