Abstract
Background: Direct oral anticoagulants (DOACs) are slowly replacing warfarin for the prevention of stroke in atrial fibrillation and treatment and secondary prevention of venous thromboembolism. Patients with poor time in therapeutic range (TTR) are often switched to a DOAC. Poor TTR can be due to drug interactions but if the reason is poor compliance, outcomes could be worse using a DOAC without monitoring.
Methods: To understand the compliance patterns we performed a retrospective chart review in patients from the anticoagulation clinic at Hamilton General Hospital that were switched from warfarin to a DOAC from April 2013 to April 2018. Patients who were taking warfarin for ≥ 2 months for any indication, except for mechanical valve prosthesis, and who were switched to a DOAC were included. We excluded patients who had a DOAC-to-DOAC switch, patients who had no reported TTR available, and those who were temporarily on warfarin after cardiac surgery. The documented reasons for a switch from warfarin to a DOAC were compared between patients with TTR ≤ 60% and >60%. Non-adherence to international normalized ratio (INR) monitoring was considered if >20% of tests were not done or delayed for more than 2 days.
Results: A total of 643 eligible patients were initially screened and 288 patients were excluded: 179 had no available TTR, 93 were temporarily on warfarin after cardiac surgery, 11 were not actually switched from warfarin to a DOAC, and 5 had a DOAC-to-DOAC switch. The remaining 355 patients were included in the analysis: 223 had a TTR ≤ 60% and 132 patients had a TTR >60%. There were no differences in the median age or gender distribution. The most common indication for anticoagulation was atrial fibrillation in both groups. The median TTR was 43% in the TTR ≤ 60% group and 71% in the TTR >60% group. The median duration on anticoagulation with warfarin was significantly longer for the TTR >60% group compared with the TTR ≤ 60% group (42 months versus 19 months; P <0.001). Apixaban was the most common DOAC of choice for the switch in both groups. The most common documented reasons for a switch in the group with a TTR >60% were: switch by another physician for unknown reason (n=36), bleeding (n=30), and patient preference (n=20). The most common reasons for a switch in those with a TTR ≤ 60% were: unstable INR readings (n=42), drug interactions (n=33), and bleeding (n=30). There was no significant difference in the rate of non-adherence with the scheduled INR monitoring (42% in the group with a TTR >60% versus 49% in those with a TTR ≤ 60%).
Conclusion: We found that about half of the patients on chronic anticoagulation with warfarin and switched to a DOAC were non-adherent with the scheduled INR monitoring. This, in combination with low TTR, should alert the physician of possible non-compliance with taking DOACs. Further prospective studies are needed to examine the DOAC adherence rate and clinical outcomes in this specific population.
Disclosures
Schulman: Boehringer-Ingelheim: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria; Sanofi: Honoraria; Bayer: Honoraria.
In Vitro Assessment of Pharmacokinetic Drug-Drug Interactions of Direct Oral Anticoagulants: Type 5-Phosphodiesterase Inhibitors Are Inhibitors of Rivaroxaban and Apixaban Efflux by P-Glycoprotein
