Physicians treating heart disease with anti-coagulants should factor the presence of kidney disease into their decisions on medications.

Physicians treating heart disease with anti-coagulants should factor the presence of kidney disease into their decisions on medications.New research led by Nita A. Limdi at the University of Alabama at Birmingham reports that the presence of chronic kidney disease is a major factor affecting the efficacy and safety of anticoagulant medications taken to prevent blood clots. The findings, reported in Clinical Pharmacology and Therapeutics, shine a spotlight on the effects of chronic kidney disease on the outcomes of patients taking traditional anticoagulants or newer direct-acting oral anticoagulants.  

Patients with cardiovascular disease are frequently prescribed anticoagulants to prevent blood clots from forming and potentially leading to stroke or systemic embolism. The new study looked at traditional anticoagulants such as warfarin, and a newer class of direct-acting anticoagulants, such as apixaban, dabigatran and others. 

“Chronic kidney disease is a common comorbidity among patients taking direct‐acting oral anticoagulants, known as DOACs,” said Nita A. Limdi, PharmD, PhD, professor in the Department of Neurology in the UAB School of Medicine, and first author of the study. “Our study evaluated the influence of kidney function on stroke or systemic embolism and hemorrhage among patients on DOACs and warfarin. To our knowledge, this is the first publication detailing the representation of patients across the kidney function spectrum and addressing key knowledge gaps by presenting the primary safety and efficacy end points by degree of kidney impairment.” 

The investigators looked at records of participants in three major studies involving anticoagulants, the RE-LY, ARISTOTLE and ENGAGE studies.

“The effect of severely impaired kidney function on drug response has long been recognized,” Limdi said. “We did not know the influence or size of the effect on the relative risk or benefit in patients with moderate kidney impairment. This study demonstrates and quantifies the influence of kidney function on the safety and efficacy of oral anticoagulants, giving clinicians a guide for prescribing anticoagulant medications to their patients with kidney disease.” 

The study results indicated that the reduction in the risk of stroke or systemic embolism provided by warfarin and dabigatran was lower among patients with compromised kidney function. The results also demonstrated a significantly increased risk of major hemorrhage among warfarin‐treated and DOAC‐treated patients with compromised kidney function. This effect was consistent, with increased risk of hemorrhage observed for dabigatran, apixaban and edoxaban, and for warfarin treated‐patients across the DOAC trials. The increased risk of hemorrhage among patients with compromised kidney function significantly lowers the net benefit of treatment.  

Nita A. Limdi, PharmD, PhD. Among patients with cardiovascular disease, the prevalence of chronic kidney disease is as high as 30-40%. The research team says it is widely recognized that the two conditions influence outcomes related to the other, and their co‐management remains challenging.  

Cardiovascular disease is the leading cause of death for patients with chronic kidney disease, and patients with moderate kidney disease are more likely to die of cardiovascular disease than to progress to kidney failure. Chronic kidney disease is a public health problem affecting 8-16% of people worldwide and 13-15%, an estimated 31 million people, in the United States.

“Our findings suggest that kidney function should be considered in estimating individual risk-benefit to inform oral anticoagulant treatment,” Limdi said. “Clinical trials should include appropriate representation of patients with impaired kidney function and report medication safety and efficacy across the spectrum of kidney function at thresholds that can inform decision-making.” 

The study was partially supported by grants from the National Institutes of Health, R01HL092173 and K24HL133373, and the Oak Ridge Institute for Science and Education (ORISE) Research Participation Program at the U.S. Food and Drug Administration.