Direct Oral Anticoagulants Linked with Higher Bleeding Risk in Patients with Chronic Kidney Disease

Highlights

• Compared with warfarin use, direct oral anticoagulant use was linked with a 23% higher risk of bleeding in patients with chronic kidney disease.
• There was no difference between direct oral anticoagulant and warfarin users in benefits from prevention of ischemic stroke.

Washington, DC (July 12, 2018) — Certain blood thinners approved to treat atrial fibrillation may put patients with chronic kidney disease (CKD) at a higher risk of bleeding, according to the results of a study in an upcoming issue of the Clinical Journal of the American Society of Nephrology (CJASN).

Direct oral anticoagulants, which are a certain type of blood thinners used to treat atrial fibrillation, are cleared by the kidneys to varying degrees, and their elimination is slower in individuals with CKD. This may predispose these patients to drug accumulation and a greater risk of bleeding events. Although all randomized clinical trials of direct oral anticoagulants have excluded patients with severe kidney dysfunction, these medications have been approved by the US Food and Drug Administration for use in patients with advanced kidney disease.

Given that approximately one-quarter of patients with atrial fibrillation have CKD, the real-world safety and effectiveness of direct oral anticoagulants in patients with atrial fibrillation across the spectrum of kidney function is of great public health importance. To investigate, Jung-Im Shin, MD, PhD (Johns Hopkins University) and her colleagues examined 2010–2017 information from the electronic health records of 3206 patients with atrial fibrillation who used direct oral anticoagulants and similar 3206 patients with atrial fibrillation who used the conventional anticoagulant warfarin.

There were 1181 bleeding events and 466 ischemic strokes over 7391 person-years of follow-up. (A person-year is the number of years of follow-up multiplied by the number of people in the study.) In patients without CKD, the risk of bleeding and benefits of preventing ischemic stroke between direct oral anticoagulant and warfarin use were similar. On the other hand, patients with CKD who took direct oral anticoagulants had 23% higher risk of bleeding compared with those on warfarin, but similar benefits from prevention of ischemic stroke.  

“Despite sparse evidence in safety and effectiveness of direct oral anticoagulants in CKD, we saw that prescription of direct oral anticoagulants in the CKD population increased substantially over time. We also found that direct oral anticoagulant use was linked with a higher risk of bleeding compared to warfarin use in patients with CKD.” said Dr. Shin.

The findings suggest the need for caution in prescribing direct oral anticoagulants in patients with CKD.

Study co-authors include Alex Secora, MPH, G. Caleb Alexander, MD, MS, Lesley A. Inker, MD, MS, Josef Coresh, MD, PhD, Alex R. Chang, MD, MS, and Morgan E. Grams, MD, PhD.

Disclosures: G.C.A. is Chair of the US Food and Drug Administration’s Peripheral and Central Nervous System Advisory Committee; has served as a paid consultant to IQVIA and serves on the Advisory Board of MesaRx Innovations; holds equity in Monument Analytics, a health care consultancy whose clients include the life sciences industry as well as plaintiffs in opioid litigation; and serves as a member of OptumRx’s Pharmacy and Therapeutics Committee. This arrangement has been reviewed and approved by the Johns Hopkins Bloomberg School of Public Health.

The article, entitled “Risks and Benefits of Direct Oral Anticoagulants across the Spectrum of Glomerular Filtration Rate among Incident and Prevalent Patients with Atrial Fibrillation,” will appear online at http://cjasn.asnjournals.org/ on July 12, 2018, doi: 10.2215/CJN.13811217.

The content of this article does not reflect the views or opinions of The American Society of Nephrology (ASN). Responsibility for the information and views expressed therein lies entirely with the author(s). ASN does not offer medical advice. All content in ASN publications is for informational purposes only, and is not intended to cover all possible uses, directions, precautions, drug interactions, or adverse effects. This content should not be used during a medical emergency or for the diagnosis or treatment of any medical condition. Please consult your doctor or other qualified health care provider if you have any questions about a medical condition, or before taking any drug, changing your diet or commencing or discontinuing any course of treatment. Do not ignore or delay obtaining professional medical advice because of information accessed through ASN. Call 911 or your doctor for all medical emergencies. 

Since 1966, ASN has been leading the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients. ASN has more than 18,000 members representing 112 countries. For more information, please visit www.asn-online.org or contact the society at 202-640-4660.

# # #