Indications for suboptimal low‐dose direct oral anticoagulants for non‐valvular atrial fibrillation patients

Abstract

BackgroundDirect oral anticoagulants (DOACs) have been developed for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). We conducted a retrospective cohort study of patients with NVAF who were newly treated with DOACs in a real-world clinical setting.MethodsWe retrospectively analyzed patients with NVAF newly treated with one of three DOACs—dabigatran, rivaroxaban, or apixaban—between January 1, 2013, and December 31, 2015.ResultsA total of 670 patients with NVAF who were newly prescribed one of the three DOACs were analyzed; 74 patients (10.9%) received dabigatran, 290 (43.3%) received rivaroxaban, and 306 (45.8%) received apixaban. Fifteen patients had thromboembolic events, almost half of which were due to discontinuation of DOACs. Six patients had major bleeding, although almost all were discharged with good neurological prognoses. A total of 129 patients were treated with a suboptimal low-dose DOAC; none experienced a thromboembolic event as long as the DOAC was taken regularly, and none of the patients in any of the three DOAC groups had major bleeding events.ConclusionsWith good adherence, the clinical course associated with DOACs is comparatively good. In the future, suboptimal low-dose DOAC therapy may serve as an appropriate choice for some patients with a high risk of stroke and bleeding.

Impact of direct oral anticoagulant off‐label doses on clinical outcomes of atrial fibrillation patients: A systematic review

“…(C) Real‐world studies results concerning dose adjustments of apixaban. (D) Results from direct oral anticoagulants overall adjustments regarding dose appropriateness…”

“…Underdosing may have important implications, as rates of systemic embolism, stroke, major bleeding and mortality are generally higher for patients receiving the lower vs higher DOAC dose . However, some studies suggest that, in the future, suboptimal low‐dose DOAC therapy may serve as an appropriate choice for some patients with a high risk of stroke and bleeding …”

“…Canadian study, 44 where a total of 47 patients were included, among (D) Results from direct oral anticoagulants overall adjustments regarding dose appropriateness 5,9,11,25,27,28,32,34,37,39,40,42,44,[47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64] whom 25 (53%) were receiving apixaban inconsistent with the ARIS-TOTLE trial and the product monograph.…”

“…However, these recommendations are not uniform worldwide, hampering the selection of the preferable posology and the identification of DOAC suboptimal use. Indeed, the approved doses and dose adjustment criteria defined by European Medicine Agency (EMA) and Food and Drugs Administration (FDA) are summarized in Table while the recommendations reported by Health Canada regulatory agency, European Society of Cardiology and Japanese guidelines, regarding DOAC dose adjustment in patients with AF, are presented in Table . Note that Japanese guidelines mention some differences in relation to EMA and FDA, particularly related to the smaller body size, different pharmacokinetic and genetic profiles of Asian populations when compared with European or American patients.…”

“…Indeed, the approved doses and dose adjustment criteria defined by European Medicine Agency (EMA) and Food and Drugs Administration (FDA) are summarized in Table 1 16,[18][19][20][21][22][23][24][25][26][27][28][29][30][31] while the recommendations reported by Health Canada regulatory agency, European Society of Cardiology and Japanese guidelines, regarding DOAC dose adjustment in patients with AF, are presented in Table 2. 7,19,[32][33][34][35][36][37][38][39][40] Note that Japanese guidelines mention some differences in relation to EMA and FDA, particularly related to the smaller body size, different pharmacokinetic and genetic profiles of Asian populations when compared with European or American patients. All these guidelines were, hence, herein taken into consideration to assess whether DOAC dose adjustment were justified or not and, therefore infer about the impact of DOAC off-label doses on clinical outcomes of patients with AF.…”