Standard and reduced doses of dabigatran, rivaroxaban and apixaban for stroke prevention in atrial fibrillation: a nationwide cohort study

TY - JOUR

T1 - Standard and reduced doses of dabigatran, rivaroxaban and apixaban for stroke prevention in atrial fibrillation

T2 - a nationwide cohort study

AU - Staerk, L

AU - Gerds, T A

AU - Lip, G .Y. H.

AU - Ozenne, B.

AU - Bonde, A. N.

AU - Lamberts, M.

AU - Fosbøl, E. L.

AU - Torp-Pedersen, C.

AU - Gislason, G. H.

AU - Olesen, J. B.

N1 - © 2017 The Association for the Publication of the Journal of Internal Medicine.

PY - 2018/1

Y1 - 2018/1

N2 - BACKGROUND: Comparative data of non-vitamin K antagonist oral anticoagulants (NOAC) are lacking in patients with atrial fibrillation (AF).OBJECTIVE: We compared effectiveness and safety of standard and reduced dose NOAC in AF patients.METHODS: Using Danish nationwide registries, we included all oral anticoagulant-naïve AF patients who initiated NOAC treatment (2012-2016). Outcome-specific and mortality-specific multiple Cox regressions were combined to compute average treatment effects as 1-year standardized differences in stroke and bleeding risks (g-formula).RESULTS: Amongst 31 522 AF patients, the distribution of NOAC/dose was as follows: dabigatran standard dose (22.4%), dabigatran-reduced dose (14.0%), rivaroxaban standard dose (21.8%), rivaroxaban reduced dose (6.7%), apixaban standard dose (22.9%), and apixaban reduced dose (12.2%). The 1-year standardized absolute risks of stroke/thromboembolism were 1.73-1.98% and 2.51-2.78% with standard and reduced NOAC dose, respectively, without statistically significant differences between NOACs for given dose level. Comparing standard doses, the 1-year standardized absolute risk (95% CI) for major bleeding was for rivaroxaban 2.78% (2.42-3.17%); corresponding absolute risk differences (95% CI) were for dabigatran -0.93% (-1.45% to -0.38%) and apixaban, -0.54% (-0.99% to -0.05%). The results for major bleeding were similar for reduced NOAC dose. The 1-year standardized absolute risk (95% CI) for intracranial bleeding was for standard dose dabigatran 0.19% (0.22-0.50%); corresponding absolute risk differences (95% CI) were for rivaroxaban 0.23% (0.06-0.41%) and apixaban, 0.18% (0.01-0.34%).CONCLUSIONS: Standard and reduced dose NOACs, respectively, showed no significant risk difference for associated stroke/thromboembolism. Rivaroxaban was associated with higher bleeding risk compared with dabigatran and apixaban and dabigatran was associated with lower intracranial bleeding risk compared with rivaroxaban and apixaban.

AB - BACKGROUND: Comparative data of non-vitamin K antagonist oral anticoagulants (NOAC) are lacking in patients with atrial fibrillation (AF).OBJECTIVE: We compared effectiveness and safety of standard and reduced dose NOAC in AF patients.METHODS: Using Danish nationwide registries, we included all oral anticoagulant-naïve AF patients who initiated NOAC treatment (2012-2016). Outcome-specific and mortality-specific multiple Cox regressions were combined to compute average treatment effects as 1-year standardized differences in stroke and bleeding risks (g-formula).RESULTS: Amongst 31 522 AF patients, the distribution of NOAC/dose was as follows: dabigatran standard dose (22.4%), dabigatran-reduced dose (14.0%), rivaroxaban standard dose (21.8%), rivaroxaban reduced dose (6.7%), apixaban standard dose (22.9%), and apixaban reduced dose (12.2%). The 1-year standardized absolute risks of stroke/thromboembolism were 1.73-1.98% and 2.51-2.78% with standard and reduced NOAC dose, respectively, without statistically significant differences between NOACs for given dose level. Comparing standard doses, the 1-year standardized absolute risk (95% CI) for major bleeding was for rivaroxaban 2.78% (2.42-3.17%); corresponding absolute risk differences (95% CI) were for dabigatran -0.93% (-1.45% to -0.38%) and apixaban, -0.54% (-0.99% to -0.05%). The results for major bleeding were similar for reduced NOAC dose. The 1-year standardized absolute risk (95% CI) for intracranial bleeding was for standard dose dabigatran 0.19% (0.22-0.50%); corresponding absolute risk differences (95% CI) were for rivaroxaban 0.23% (0.06-0.41%) and apixaban, 0.18% (0.01-0.34%).CONCLUSIONS: Standard and reduced dose NOACs, respectively, showed no significant risk difference for associated stroke/thromboembolism. Rivaroxaban was associated with higher bleeding risk compared with dabigatran and apixaban and dabigatran was associated with lower intracranial bleeding risk compared with rivaroxaban and apixaban.

KW - Administration, Oral

KW - Aged

KW - Anticoagulants/administration & dosage

KW - Atrial Fibrillation/complications

KW - Cohort Studies

KW - Dabigatran/administration & dosage

KW - Denmark

KW - Dose-Response Relationship, Drug

KW - Female

KW - Hemorrhage/chemically induced

KW - Humans

KW - Male

KW - Pyrazoles/administration & dosage

KW - Pyridones/administration & dosage

KW - Registries

KW - Rivaroxaban/administration & dosage

KW - Stroke/etiology

U2 - 10.1111/joim.12683

DO - 10.1111/joim.12683

M3 - Journal article

C2 - 28861925

SN - 0954-6820

VL - 283

SP - 45

EP - 55

JO - Journal of Internal Medicine

JF - Journal of Internal Medicine

IS - 1

ER -