Challenges of DOAC Use Among Patients With VTE, CKD Who Are At Higher Risk of Death, Major Bleeding

^{By Julie Gould}

According to a recent study, patients with venous thromboembolism (VTE) with concomitant moderate to severe chronic kidney disease (CKD) area at an increased risk of death, VTE recurrence, and major bleeding. The findings of this study were published online in JAMA Network Open.

“Patients with VTE and concomitant CKD have been reported to have a higher risk of thrombosis and major bleeding complications compared with patients without concomitant CKD,” explained the study authors. “The use of anticoagulation therapy is challenging, as many anticoagulant medications are excreted by the kidney. Large-scale data are needed to clarify the impact of CKD for anticoagulant treatment strategies and clinical outcomes of patients with VTE.” 

To better understand the study design and findings, we spoke with lead researcher, Shinya Goto, MD, PhD, FACC, professor in the Department of Medicine (Cardiology), Tokai University School of Medicine. He discusses the study, and explains why the use of anticoagulants are not easy in advanced CKD patients because orally available direct anticoagulants can be excreted by the kidneys. 

What existing data led you and your co-investigators to conduct this research? 

The 3 of direct oral anticoagulants (DOACs) were developed clinically for prevention and treatment of VTE. Highly advanced CKD patients were excluded in the clinical trials. The number of patients with advance CKD are limited in the trials. The real world use of DOACs in advanced CKD patients and their clinical outcomes are still to be elucidated. Despite existing data suggested worse clinical outcomes in advanced CKD patients, but these available data have obvious limitations such as the data were collected before wide spread use of DOAC, patients were recruited only from specific regions of the world, retrospective analysis, and so on. Thus, we were motivated to clarify the clinical outcomes of VTE patients accompanying with advanced CKD with the use of prospectively collected global dataset.   

Please briefly describe your study and its findings. Were any of the outcomes particularly surprising? 

In the GARFIELD (Global Anticoagulant Registry in the Field)-VTE registry, we have successfully recruited more than 10,000 patients with objectively confirmed newly diagnosed venous thromboembolism patients from 25 countries. It is of note that patients were recruited from various regions of the world including the Europe, the South and North American, Africa, Middle East, and Asia. There are non specific therapeutic intervention recommended at GARFIELD-VTE. Thus, our database represent the current real world practice for VTE patients on the globe.  

Our current analysis of 8979 patients whose creatine values are available demonstrate that the patients with moderate to severe CKD stage had a higher risk of all-cause mortality (adjusted hazard ratio [aHR], 1.44; 95% CI, 1.21-1.73), major bleeding (aHR, 1.40; 95% CI, 1.03-1.90), and recurrent VTE (aHR, 1.40; 95% CI, 1.10-1.77) than patients with mild to no CKD. CKD is quite common in aging society. The use of anticoagulants are not easy in advanced CKD patients because orally available direct anticoagulants were excreted by kidney at least in part. Our research show the clear unmet needs in the field of common in hospital disease of venous thromboembolism accompanying with common disease of chronic kidney disease. The most surprising part of our research is approximately one eight of patients with moderate to severe CKD disease within 12 month. (12.8 deaths per 100 person-years [95% CI, 11.3-14.6 deaths per 100 person-years]). The unmet medical need for VTE with advanced CKD for prevention of death is clarified by our research.  

What are the possible real-world applications of these findings in clinical practice?

The GARFIELD (Global Anticoagulant Registry in the Field)-VTE registry reflect real-world practice for objective confirmed VTE on the globe. Thus, our results raise alert for all the physicians taking care of VTE patients with moderate-to-severe CKD that these patients are at high risks for death, severe bleeding and VTE recurrence.  

Do you and your co-investigators intend to expand upon this research?

Yes, we do. With the use of precise database of GARFIELD-VTE, we aim to further identify patients at future clinical events from baseline data, such as anemia, thrombocytosisi, etc.

Is there anything else pertaining to your research and findings that you would like to add?

Recent advance in computer technology allow us handle multi-dimensional data quantitatively. Machine learning and artificial intelligence should provide more opportunity to identify high risk patients from clinical database. We are aim the world where all medical data could be handled to predict future clinical events in individual patients.  

About Dr Goto:

Dr Goto was trained as clinical cardiologists at Keio University School of Medicine (Tokyo, Japan), then underwent post-doctoral research training in cell and molecular biology in the field of platelet function and thrombus formation. In combining these 2 expertises together, he has worked as the thrombo-cardiologists in both clinical and basic research. The analysis of large scale international cohort such as GARFIELD-VTE project is one of his preferable projects to conduct.

Reference:

Goto S, Haas S, Ageno W, et al. Assessment of Outcomes Among Patients With Venous Thromboembolism With and Without Chronic Kidney Disease. JAMA Netw Open. 2020;3(10):e2022886. Published 2020 Oct 1. doi:10.1001/jamanetworkopen.2020.22886