Study evaluates use of novel oral anticoagulants in ICU

Dr Kalabalik

Approximately one-third of patients on a novel oral anticoagulant (NOAC) received inappropriate dosing based on indication, renal function, or concomitant interacting medications during hospitalization in the intensive care unit, typically for stroke prevention in atrial fibrillation, according to data presented at the Society of Critical Care Medicine meeting in Phoenix.

Julie Kalabalik, PharmD, of Fairleigh Dickinson University School of Pharmacy, Florham Park, N.J., and colleagues conducted a retrospective chart review that included all medical intensive care unit patients greater than or equal to 18 years of age who received dabigatran, rivaroxaban, or apixaban from June 2013 through May 2014. Patients excluded were those less than 18 years of age, pregnancy, presence of prosthetic heart valve, or active bleeding. 

What's new in the drug anticoagulant antidote market?

The researchers found that 7 out of 21 medical intensive care unit (ICU) patients received an inappropriate dose of a novel oral anticoagulant (dabigatran, rivaroxaban, or apixaban) at some point during their ICU stay (2 dabigatran, 2 rivaroxaban, 3 apixaban).

AHA: Rivaroxaban linked to fewer hospital days compard to warfarin in NVAF patients

The majority of inappropriate NOAC dosing was due to either concomitant interacting medications in the presence of renal impairment or incorrect dosing based on renal function (6 out of 7 or 86%). One patient (1 out of 7 or 14%) was inappropriately dosed based on indication. One patient (1 out of 21 or 5%) who received apixaban experienced a bleeding event. Two patients received inappropriate dosing while being converted from or to an alternate anticoagulant.

No hemodialysis or prothrombin complex concentrate was utilized in any of the patients included in this study. Mean age of patients in this study was 74.5 years, with 52% male. The mean weight was 91.9 kg and mean serum creatinine was 1.3 mg/dL. The indication for NOAC use in the majority of patients was stroke prevention in nonvalvular atrial fibrillation (76%) and the remainder for prevention or treatment of venous thromboembolism (24%).

“Novel oral anticoagulants include direct thrombin inhibitors [dabigatran) and factor Xa inhibitors [rivaroxaban, apixaban],” said Dr Kalabalik. “Edoxaban is also a factor Xa inhibitor and was just approved by the FDA this month.

“The advantages of these newer anticoagulants include rapid onset and offset of action, lack of routine coagulation monitoring as is required with vitamin K antagonists, and fewer drug and food interactions,” she said.

However, of notable concern is the lack of an antidote for these newer anticoagulants, said Dr Kalabalik. “This is especially important for patients who may require urgent surgery or who have severe bleeding while receiving NOACs. Elimination of NOACs is dependent on renal function and there is concern of drug bioaccumulation and potential increased risk of bleeding in the setting of renal impairment.”

Additionally, concomitant administration of cytochrome P450 and P-glycoprotein inhibitors affects serum levels of NOACs and impact dosing recommendations.

“There is a lack of data with use of these agents in the critically ill population,” she said. “This population is especially vulnerable to rapid fluctuations in renal impairment and patients are often receiving multiple medications, increasing the risk for potential drug-drug interactions. NOACs are more expensive than vitamin K antagonists. Formulary managers in the hospital setting are in an optimal position to determine the appropriateness of use of NOACs in various patient populations.”