Drug-related problems associated with direct oral anticoagulants: an observational cross-sectional study of medical record review by pharmacists in a large teaching hospital

Background Prescribing DOACs presents with challenges in the elderly and patients with renal and hepatic impairment. To mitigate safety risks, pharmacists have a role in detection, prevention, and resolution of DOAC-associated drug-related problems (DRPs). Objectives To identify the types of DOAC-associated DRPs in patients on DOAC therapy and factors that predispose patients to DOAC-associated DRPs. Methods An observational cross-sectional study was conducted in SGH from January 1, 2017, to May 31, 2019, on patients prescribed with a DOAC (rivaroxaban, dabigatran, and apixaban). Data were electronically extracted for patient demographics, clinical characteristics, and details of DOAC-related DRPs identified by pharmacists. Matching of DRP group to non-DRP group at a ratio of 1:2 based on gender, race, and DOAC was performed. The DRP group included patients with detected DRPs while non-DRP group included patients without them. Descriptive analysis was used to summarize patient characteristics and types of DOAC-associated DRPs. In the matched population, conditional logistic regression was used to calculate unadjusted (UOR) and adjusted odds (AOR) ratio to detect association of DOAC-associated DRPs with age, renal function, ≥2 comorbidities, and DOAC indication (atrial fibrillation [AF] vs venous thromboembolism). Results A total of 8432 patients prescribed DOACs were analyzed, which consisted of 827 (9.8%) and 7602 (90.2%) patients with DRPs and no DRPs, respectively. The top DOAC-associated DRP was inappropriate drug regimen ( n = 487, 60.1%). After matching, 2403 patients were analyzed, consisting of 801 patients from DRP group and 1602 from non-DRP group. Factors associated with DOAC-associated DRPs were statistically significant for renal function at creatinine clearance (CrCl) of >30 to 50 mL/min/1.73 m 2 (AOR: 1.42; 95% CI: 1.14-1.76; P = .002), 15 to 30 mL/min/1.73 m 2 (OR: 1.94; 95% CI: 1.42-2.66; P < .001), and <15 mL/min/1.73m 2 (OR: 2.35; 95% CI: 1.13-4.88; P = .022), respectively, compared with a CrCl of >50 mL/min/1.73 m 2 and DOAC indication for AF (AOR: 1.84; 95% CI: 1.47-2.30; P < .001) compared with venous thromboembolism. Conclusion Inappropriate drug regimen was the most common DOAC-associated DRP. Impaired renal function and patients with AF increased the likelihood of DOAC-associated DRPs.