Timing of Off-Label Dosing of Direct Oral Anticoagulants in Three Large Health Systems.

BACKGROUND: While direct oral anticoagulants (DOACs) may be viewed as simpler to manage then warfarin, they present their own unique management challenges resulting in frequent off-label dosing. It is unknown to what extent off-label dosing occurs when a patient is started on a DOAC versus later in their treatment. OBJECTIVES: We aimed to characterize when off-label DOAC dosing is occurring and to evaluate the effectiveness of prescribing oversight using a registry-based intervention. METHODS: We evaluated data from the Michigan Anticoagulation Quality Improvement Initiative (MAQI2) registry, a retrospective quality improvement process using data abstractors, from 2018 - 2022 on the number of "alerts" that are generated in response to dosing deviating from evidence-based guidelines. RESULTS: Among a sample of 1,261 to 1,563 annual DOAC-treated patients in the MAQI2 registry, off-label dosing was relatively common. Over the 5-year period from 2018 through 2022, there were 735 total dosing alerts. Alerts occurred more frequently during a follow-up than at the time of initial prescribing, 69.0% (507) versus 31.0% (228) respectively. After initial review by quality improvement abstractors, 18.2% of alerts (134) resulted in contact to the prescriber. When the prescriber was contacted, it led to an intervention 74.6% of the time. The most common intervention was a change in DOAC dosing. CONCLUSIONS: This study demonstrates the benefit of DOAC prescribing oversight using a registry-based intervention to monitor for off-label dosing for the entirety of the time period a patient is prescribed DOAC as deviations in evidence-based prescribing occur frequently during the follow-up period.

Review of the Ticagrelor Trials Evidence Base.

Ticagrelor is a platelet P2Y12 receptor inhibitor approved for use in patients with acute coronary syndromes, coronary artery disease, and low-moderate risk acute ischemic stroke or high-risk transient ischemic attack. Clinical trials have evaluated the efficacy and safety of ticagrelor on ischemic and bleeding outcomes for different indications and with varying treatment approaches. As a result, there is a large body of clinical evidence demonstrating different degrees of net clinical benefit compared with other platelet inhibitor drugs based on indication, patient characteristics, clinical presentation, treatment duration, and other factors. We provide a review of the major trials of ticagrelor in the context of other randomized trials of clopidogrel and prasugrel to organize the volume of available information, elevate corroborating and conflicting data, and identify potential gaps as areas for further exploration of optimal antiplatelet treatment.