What this Trial Is About

Direct oral anticoagulants (DOACs) have emerged as safe and efficacious ischemic stroke prophylaxis for non-valvular atrial fibrillation (NVAF). All four DOACs - apixaban, dabigatran, edoxaban, and rivaroxaban - were shown to reduce the risk of major bleeding compared to warfarin. The predictable pharmacokinetic profiles of DOACs also favour their use over warfarin. Together with increasing AF incidence due to population ageing, increased AF detection, and territory-wide reimbursement schemes, DOAC prescriptions have been surging worldwide. In Hong Kong, more than 78,354 patients received DOAC from January 2009 through April 2021 according to the Hospital Authority registry. The more liberal use of DOACs has led to new issues that require a thorough understanding of ethnic-specific DOAC pharmacokinetic profiles. For instance, 12- 15% of anticoagulated patients annually required interventional procedures that involve temporary discontinuation of DOAC for 48 hours or more. Although guideline-based periprocedural DOAC interruption resulted in a low 30-day thromboembolism rate of 0.16% - 0.6% in a Caucasian cohort, same measures for elective colonoscopies in a local population-based study resulted in a 30-day periprocedural thromboembolism rate of up to 2.2%. Although these studies cannot be compared directly, the remarkable interethnic discrepancy between the two cohorts warrants further pharmacokinetic and pharmacogenomic studies. More importantly, quantifying residual DOAC levels during the interruption periods may imply on duration of periprocedural DOAC interruption, length of hospital-stay, and the risk of thromboembolic and bleeding complications. Mapping inter- and intra-individual variations in DOAC levels may also impact on the management of ischemic stroke among DOAC recipients. Epidemiological studies have shown alarmingly up to 13% of acute ischemic stroke patients were on anticoagulation prior to stroke onset with increasing number of DOAC. These patients received low rates of recanalization therapy due to apprehension of bleeding complications, thus compromised survival and neurological recovery. A prospective study that reveals Asian-specific DOAC pharmacokinetic profiles may inform cross-disciplinary, territory-wide periprocedural care and acute stroke intervention strategy for the rapidly expanding DOAC population.

DOAC in Chinese Patients With Atrial Fibrillation