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Semin Thromb Hemost 2019; 45(02): 196-204
DOI: 10.1055/s-0038-1657783
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

New Anticoagulant Agents: Incidence of Adverse Drug Reactions and New Signals Thereof

Carlos Treceño-Lobato
1   Consejo de Colegios Profesionales de Farmacéuticos de Castilla y León, Castilla y León, Spain
2   Departamento de Ciencias de la Salud, Facultad de Ciencias de la Salud, Universidad Europea Miguel de Cervantes (UEMC), Valladolid, Spain
,
María-Isabel Jiménez-Serranía
1   Consejo de Colegios Profesionales de Farmacéuticos de Castilla y León, Castilla y León, Spain
2   Departamento de Ciencias de la Salud, Facultad de Ciencias de la Salud, Universidad Europea Miguel de Cervantes (UEMC), Valladolid, Spain
,
Raquel Martínez-García
1   Consejo de Colegios Profesionales de Farmacéuticos de Castilla y León, Castilla y León, Spain
,
Francisco Corzo-Delibes
3   Consejería de Sanidad de la Junta de Castilla y León, Dirección General de Salud Pública (DGSP), Valladolid, Spain
,
Luis H. Martín Arias
4   Centro Regional de Farmacovigilancia de Castilla y León, Centro de Estudios sobre la Seguridad de los Medicamentos (CESME), Facultad de Medicina, Universidad de Valladolid, Valladolid, Spain
› Author Affiliations
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Publication History

Publication Date:
04 June 2018 (online)

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Abstract

The aim of this study was to evaluate the adverse drug reaction (ADR) incidence rate and new signals thereof for classic compared with new anticoagulants in real-life ambulatory settings. The authors performed an observational cross-sectional study in two cohorts of surveyed patients treated with vitamin K antagonists (VKAs; acenocoumarol or warfarin) or nonvitamin K antagonist oral anticoagulants (NOACs; apixaban, edoxaban, rivaroxaban, dabigatran etexilate). Descriptive, clinical, and ADRs data were reported and analyzed through a bivariate analysis (odds ratio [OR]) to compare the ADRs incidence rate and an adaptation of Bayesian methodology (false discovery rate [FDR] < 0.05) to detect new signals. A total of 334 patients were surveyed—average international normalized ratio (INR) of 2.6—and 45.4% taking new anticoagulants. Note that 835 ADRs were reported; 2.5 per patient (2.8 in the VKA cohort, 2.1 in the NOAC cohort). The authors obtained higher risk of epistaxis (OR, 2.18; 95% confidence interval [CI], 1.01–4.74) and hematoma (OR, 2.43; 95% CI, 1.39–4.25) with VKAs and lower risk of global bleeding symptoms with NOACs (OR, 0.45; 95% CI, 0.28–0.71). After standardizing the data, a significant risk of diarrhea with VKAs was observed (OR, 3.37; 95% CI, 1.09–10.41). They also detected an intense positive signal regarding the use of VKAs and osteoporosis (FDR < 0.001), specifically acenocoumarol (FDR < 0.002). NOACs presented lower risk of bleeding, especially dabigatran (FDR < 0.031), and of dermatological pathologies with apixaban being the safest (FDR = 0.050). The lower risk of global bleeding and a potential protective effect against osteoporosis in patients treated with NOACs postulate them as safer than VKAs.

Keywords

new oral anticoagulant - vitamin K antagonist - bleeding - osteoporosis

Grant Support

The Sentinel network in Castilla y León received financial support from Daiichi Sankyo España S.A.U. to assume the administrative cost of the project.