From the Journals

NOACs benefit early stage chronic kidney disease patients

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Consider NOACs for early chronic kidney disease

The significant reduction in risk of hemorrhagic stroke, recurrent venous thromboembolism, and VTE-related deaths in patients with early-stage chronic kidney disease given a NOAC [non–vitamin K oral anticoagulants] in a meta-analysis supports clinical application, but is there a level of renal dysfunction for which clinicians should apply greater caution in extrapolating these findings? As the evidence supporting the safety and effectiveness of NOACs in the general population increases, there is a renewed interest in defining the role of anticoagulant therapy to prevent stroke and VTE in patients with chronic kidney disease and end-stage kidney disease. This interest is driven in part by uncertainty as to the benefits vs. harms of warfarin for patients with chronic kidney disease. The data in the meta-analysis by Ha and colleagues do not support any benefits for patients with end-stage disease, but the results of two ongoing clinical trials of patients with atrial fibrillation and end-stage kidney disease may offer insights.

Until the results of these trials become available, the decision to use anticoagulant therapy in patients with end-stage kidney disease will continue to require an individualized approach that balances potential benefits and harms.

Ainslie Hildebrand, MD, of University of Alberta, Edmonton; Christine Ribic, MD, of McMaster University, Hamilton, Ont.; and Deborah Zimmerman, MD, of the University of Ottawa, made these comments in an accompanying editorial (Ann Intern Med. 2019 July 15. doi:10.7326/M19-1504). Dr. Ribic disclosed grants from Pfizer, Leo Pharma, and Astellas Pharma. Dr. Hildebrand and Dr. Zimmerman had no financial conflicts to disclose.


 

FROM THE ANNALS OF INTERNAL MEDICINE

Non–vitamin K oral anticoagulants (NOACs) significantly reduced the risk of stroke or systemic embolism compared to vitamin K antagonists (VKAs) for patients in the early stages of chronic kidney disease and comorbid atrial fibrillation, based on data from a meta-analysis of roughly 34,000 patients.

Chronic kidney disease increases the risk of complications including stroke, congestive heart failure, and death in patients who also have atrial fibrillation, but most trials of anticoagulant therapy to reduce the risk of such events have excluded these patients, wrote Jeffrey T. Ha, MBBS, of the George Institute for Global Health, Newtown, Australia, and colleagues.

To assess the benefits and harms of oral anticoagulants for multiple indications in chronic kidney disease patients, the researchers conducted a meta-analysis of 45 studies including 34,082 individuals. The findings were published in the Annals of Internal Medicine. The analysis included 8 trials of end stage kidney disease patients on dialysis; the remaining trials excluded patients with creatinine clearance less than 20 mL/min or an estimated glomerular filtration rate less than 15 mL/min per 1.73 m2. The interventional agents were rivaroxaban, dabigatran, apixaban, edoxaban, betrixaban, warfarin, and acenocoumarol.

A notable finding was the significant reduction in relative risk of stroke or systemic embolism (21%), hemorrhagic stroke (52%), and intracranial hemorrhage (51%) for early-stage chronic kidney disease patients with atrial fibrillation given NOACs, compared with those given VKAs.

The evidence for the superiority of NOACs over VKAs for reducing risk of venous thromboembolism (VTE) or VTE-related death was uncertain, as was the evidence to draw any conclusions about benefits and harms of either NOACs or VKAs for patients with advanced or end-stage kidney disease.

Across all trials, NOACs appeared to reduce the relative risk of major bleeding, compared with VKAs by roughly 25%, but the difference was not statistically significant, the researchers noted.

The findings were limited by the lack of evidence for oral anticoagulant use in patients with advanced chronic or end-stage kidney disease, as well as inability to assess differences among NOACs, the researchers noted. However, the results suggest that NOACs may be recommended over VKAs for the subgroup of early-stage chronic kidney disease patients with atrial fibrillation, they said.

Several additional trials are in progress, and future trials “should include not only participants with dialysis-dependent ESKD [end-stage kidney disease] but also those with CrCl [creatinine clearance of] less than 25 mL/min,” and compare NOACs with placebo as well, they noted.

Lead author Dr. Ha is supported by a University Postgraduate Award from University of New South Wales, Sydney, but had no financial conflicts to disclose; coauthors disclosed support from various organizations as well as pharmaceutical companies including Baxter, Amgen, Eli Lilly, Boehringer Ingelheim, Vifor Pharma, Janssen, Pfizer, Bristol-Myers Squibb, and GlaxoSmithKline.

SOURCE: Ha JT et al. Ann Intern Med. 2019 July 15. doi: 10.7326/M19-0087

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