Prescribing DOACs with specific patient populations in mind

Effectiveness of DOACs for AF in patients with obesity isn’t clear, as most data are from retrospective cohort analyses. In patients weighing > 120 kg, dabigatran has shown efficacy in thrombosis prevention similar to that achieved in those weighing ≤ 120 kg, but it has increased the risk for gastrointestinal (GI) bleeding.¹⁵ Another study indicated a 15-mg dose of rivaroxaban may be associated with increased thromboembolic complications in patients with a BMI ≥ 35.¹⁶ Alternatively, another retrospective study of rivaroxaban demonstrated a small absolute risk reduction in ischemic stroke among patients in all stages of obesity and no difference in significant bleeding events.¹⁷ One further retrospective cohort showed that, in patients with a BMI ≥ 50 kg, the effectiveness of rivaroxaban and apixaban in thrombosis prevention and bleeding safety outcomes was comparable to that seen in those with a BMI < 30.¹⁸

As a result of conflicting data, and a lack of prospective randomized controlled trials (RCTs), ISTH continued recommending international normalized ratio (INR)–based dosing of warfarin for class 3 or severely obese patients with AF. The 2018 CHEST guidelines¹⁹ and the 2020 ESC guidelines²⁰ make no mention of DOAC avoidance in patients with obesity and AF.

Advanced and end-stage renal disease

DOACs are renally dosed based on indication, drug-drug interactions, and degree of renal function (TABLE 3^1-4). For example, patients with AF who are anticoagulated with apixaban are prescribed 2.5 mg twice daily when 2 of the 3 following criteria are met: age ≥ 80 years, body weight ≤ 60 kg, serum creatinine ≥ 1.5 mg/dL. However, no dosage adjustment is necessary for VTE treatment or prophylaxis with apixaban regardless of renal function.³

Data supporting the safety and efficacy of DOACs in end-stage renal disease (ESRD) are sparse. All DOACs are renally cleared to varying degrees (TABLE 2^1-4), theoretically increasing bleeding risk as kidney disease progresses. Apixaban is the least renally cleared of the DOACs and has been evaluated in the greatest number of trials for patients with ESRD for both VTE treatment and prevention and nonvalvular AF.²¹ As a result, the FDA approved standard-dose apixaban (5 mg twice daily) for VTE treatment and prevention and nonvalvular AF in patients with ESRD, even those requiring dialysis. Use the reduced apixaban dose (2.5 mg twice daily) in patients with ESRD and AF only if they are ≥ 80 years of age or their body weight is ≤ 60 kg.³

Patients with cancer

Cancer-associated acute VTE treatment. Cancer is an established risk factor for acute VTE but it also increases the risk for treatment-­associated bleeding compared with patients without cancer.²² Historically, low-molecular-weight heparin (LMWH) was recommended over warfarin and DOACs for cancer-associated thromboses (CAT).²³ Compared with warfarin, LMWH reduced the rate of recurrent VTE and had similar or reduced bleeding rates at 6 to 12 months.^24-26 However, clinicians and patients often chose warfarin to avoid subcutaneous injections.²⁷

CHEST guidelines recommend oral Xa inhibitors over LMWH for the treatment of CAT.¹³ The 2020 guidelines of the National Institute for Health and Care Excellence (NICE) recommend DOACs as an option for CAT along with LMWH or LMWH transitioned to warfarin.²⁸ The American Society of Clinical Oncology (ASCO) recommends rivaroxaban for acute VTE treatment in CAT. No head-to-head trials have evaluated comparative efficacy of DOACs for CAT. However, edoxaban and rivaroxaban are associated with a greater risk for GI bleeding; therefore, apixaban is preferred in patients with GI malignancies.²⁹ Standard DOAC VTE treatment dosing is recommended for all 3 agents.^2-4

When using DOACs for patients with CAT, consider potential drug-drug interactions with chemotherapy regimens. All DOACs­ are transported by p-glycoprotein, while rivaroxaban and apixaban are substrates of cytochrome P450, leading to potentially significant drug-drug interactions.³⁰ These interactions could affect the patient’s chemotherapeutic regimen, decrease the efficacy of the DOAC, or increase the risk for bleeding. Therefore, anticoagulation choice should be made in collaboration with the ­hematology/oncology team.

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