Use of direct oral anticoagulants for the prevention and treatment of thromboembolic disease in patients with reduced renal function: a short review of the clinical evidence

Abstract

BackgroundThe use of direct oral anticoagulants (DOACs) is restricted by the limitations of clinical trials guiding therapy for patients with renal impairment, as many of these trials excluded patients with severe renal impairment. There are currently four agents available: dabigatran, rivaroxaban, apixaban, and edoxaban. The purpose of this review was to 1) describe current recommended dosing for each DOAC and published postmarketing data, including case reports, on the use of these agents in the renally impaired; and 2) discuss patient adherence and satisfaction and the cost of these agents.Materials and methodsA literature search was conducted using Medline and Embase with the terms “dabigatran” or “rivaroxaban” or “apixaban” or “edoxaban” and “renal impairment”. Clinical trials and case reports describing the use of DOAC therapy in patients with renal impairment were reviewed. A second search was conducted to find articles evaluating patient adherence, patient satisfaction, and pharmacoeconomics of DOACs.ResultsThere are a multitude of subgroup and post hoc analyses, as well as six case reports with dabigatran and one case report with apixaban, that provide insight for the clinical use of DOACs in patients with renal impairment. Dabigatran exhibits the greatest level of renal elimination, and there are data from clinical trials and several case reports that warrant reconsideration before use. Other DOACs may be a better option in patients with impaired renal function. Further, data from patient-adherence studies have suggested that DOACs that are dosed daily (rather than twice daily) are optimal and preferred. There does not appear to be a cost difference between DOACs and warfarin therapy.ConclusionDOAC therapy in patients with impaired renal function requires more critical review of study data, as these patients may have increased risk of bleeding. It is also valuable to consider patient preferences and cost when selecting the appropriate option for oral anticoagulation.

Direct Oral Anticoagulant Use in Chronic Kidney Disease and Dialysis Patients With Venous Thromboembolism: A Systematic Review of Thrombosis and Bleeding Outcomes

“…Our findings are consistent with several reviews on the use of DOACs in the treatment of VTE among CKD patients (including elderly patients). 30,31 Among patients with moderate kidney impairment (CrCl = 30-49 mL/min), Parker and Thachil 32 also concluded in their review that DOACs are noninferior to VKA therapy in terms of efficacy in acute, symptomatic VTE. Our systematic review findings are also similar to the meta-analysis of 26 872 patients in the 6 RCTs comparing DOACs with VKAs for treatment of acute symptomatic DVT, PE, or both.…”

“…Similar to the case of using DOACs in atrial fibrillation for the CKD/dialysis population, there is still a lack of efficacy and safety data of using these agents for treatment of VTE in HD patients or those with severe kidney impairment. 31 Reduced doses of apixaban may be an option for VTE treatment if cautiously used in patients with moderate to severe kidney impairment. A recommendation table to help clinicians and practitioners in applying the findings from this systematic review is found in the Supplementary Material Table S3.…”

Deleting Death and Dialysis: Conservative Care of Cardio-Vascular Risk and Kidney Function Loss in Chronic Kidney Disease (CKD)

“…In spite of data suggestive of their usefulness vs. classical warfarin in the general population [ 462 ], to the best of our knowledge, insufficient information is available about their application and the health-economic impact in CKD. In addition, they should be used with care in CKD, as their renal elimination may be hampered progressively as renal function deteriorates [ 463 , 464 ].…”

Recommendations from the ICM-VTE: Hip & Knee

“…Risks may be increased in case of renal dysfunction 277 , and concomitant medications or age may also affect bleeding. Non-steroidal anti-inflammatory drugs 278,279 did not increase the risk of bleeding for dabigatran 278 , and age older than 75 280 showed lower risk of bleeding with anti-Xa medications than with LMWH (OR = 0.71).…”