Safety and Efficacy of DOACS in CKD/Dialysis

Patients with chronic kidney disease (CKD) have a higher risk of venous thromboembolism (VTE), regardless of their degree of kidney impairment. Thrombosis risk is further increased in patients with end-stage kidney disease on hemodialysis. Bleeding risk is also increased in patients with CKD compared to patients with normal renal function. Direct oral anticoagulants (DOACs; dabigatran, rivaroxaban, apixaban, edoxaban) have replaced warfarin in the management of patients with atrial fibrillation and for VTE prophylaxis and treatment. However, data are limited on the safety and efficacy of DOACs in patients with CKD. A systematic review evaluated VTE and bleeding outcomes with DOACs in CKD and dialysis patients. A total of nine studies were included; warfarin was the comparator in seven studies. Overall, there was no significant difference between DOACs and warfarin in reducing recurrent VTE or bleeding events in patients with moderate CKD (creatinine clearance [CrCl] 30–49 mL/min). As the degree of kidney impairment increased, the risk of overall major bleeding from DOACs increased. Limited evidence suggests that apixaban may lead to lower rates of major bleeding compared to warfarin in patients with end-stage kidney disease or CrCl < 25 mL/min. In dialysis patients, there was no significant difference between apixaban and warfarin for VTE outcomes. Implications for pharmacists In patients with moderate CKD, DOACs have comparable efficacy in reducing VTE outcomes and similar safety when compared to warfarin. However, data are lacking on the use of these agents in patients with VTE with severe kidney impairment or dialysis. In patients with CrCl 15–29 mL/min, dabigatran should be avoided; rivaroxaban 15 mg daily, edoxaban 30 mg daily or apixaban 5 mg twice daily can be considered in this population. Apixaban 2.5 mg twice daily may be cautiously used in patients with severe renal impairment (CrCl < 15 mL/min) or on dialysis. Reference Cheung CY, Parikh J, Farrell A, et al. Direct oral anticoagulant use in chronic kidney disease and dialysis patients with venous thromboembolism: a systematic review of thrombosis and bleeding outcomes. Ann Pharmacotherapy 2021;55:711-22. Thiazide diuretics and skin cancer Thiazide diuretics are first-line options for management of hypertension. However, previous studies have linked these agents to the development of skin cancers, including melanoma and keratinocyte carcinoma (also called nonmelanoma skin cancer, with the two main types being basal cell carcinoma and squamous cell carcinoma). Various health agencies, including Health Canada and the US Food and Drug Administration, have issued warnings about this potential association. A population-based cohort study provides further evidence that long-term exposure to thiazide diuretics is associated with a higher risk of developing skin cancer. Using administrative health data from Ontario from 1998–2017, the study included 302,634 adults over 65 years of age with a first prescription for a thiazide, angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, calcium channel blocker or beta-blocker. They were matched to 605,268 adults who were not exposed to these medications. Increasing cumulative thiazide exposure was associated with increasing rates of skin cancer. Patients exposed to more than 7.5 Defined Annual Dose units (e.g., patient taking hydrochlorothiazide 25 mg daily for 7.5 years or 12.5 mg daily for 15 years) had a 44% higher rate of keratinocyte carcinoma and a 60% higher rate of melanoma, compared to patients exposed to lower doses. No consistent evidence was found for associations between other antihypertensive classes and skin cancer. Implications for pharmacists This study shows that increasing thiazide exposure is associated with higher rates of keratinocyte carcinoma and melanoma. The authors suggest that the increased risk may be related to thiazide phototoxicity. Patients taking thiazides should consider sun protection, limiting sun exposure and monitoring for early detection of skin cancer. In patients at high risk for skin cancer, alternatives to thiazides may be considered. A statement issued by Hypertension Canada notes that the absolute risk of skin cancer is low in patients taking thiazides, estimated at one extra case of melanoma per 9,000–14,000 patients treated with a thiazide. In contrast, the risk of hypertension-related complications is high. Hypertension Canada cautions that patients should not discontinue thiazides on their own and should speak about the potential risk of skin cancer with their pharmacist or physician. Sandra Knowles, BScPhm, is a drug information pharmacist with Sunnybrook Health Sciences Centre in Toronto. References Drucker AM, Hollestein L, Weinstock MA, et al. Association between antihypertensive medications and risk of skin cancer in people older than 65 years: a population-based study. CMAJ 2021;193:E508-16. Hypertension Canada. Statement on thiazide diuretics and skin cancer. April 19, 2021. https://hypertension.ca/wp-content/uploads/2021/04/HC-thiaz-skin-cancer-HCP-final-19-04-2021-1.pdf (accessed June 28, 2021).

Safety and Efficacy of DOACS in CKD/Dialysis

Register for free access or login.

More Blog Posts in This Series

Pseudoephedrine: risk of PRES/RCVS

Do PPIs increase risk for migraine?

Safety of combining PDE5 inhibitors and nitrates

Blog Author

Sandra Knowles

Related Topics