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. 2021 May 27;10(11):2367.
doi: 10.3390/jcm10112367.

Inappropriate Use of Oral Antithrombotic Combinations in an Outpatient Setting and Associated Risks: A French Nationwide Cohort Study

Lorène Zerah  1 , Dominique Bonnet-Zamponi  2   3 , Aya Ajrouche  2 , Jean-Philippe Collet  4 , Yann De Rycke  2 , Florence Tubach  2
Affiliations

Inappropriate Use of Oral Antithrombotic Combinations in an Outpatient Setting and Associated Risks: A French Nationwide Cohort Study

Lorène Zerah et al. J Clin Med. .

Abstract

With the increase in prevalence of cardiovascular diseases, multimorbidity, and medical progress, oral antithrombotic (AT) combinations are increasingly prescribed. The aims of this study were to estimate the incidence of oral AT combinations, their appropriateness (defined as indications compliant with guidelines), and the related risk of major bleeding (i.e., leading to hospitalization) or death, among new users. We conducted a 5-year historical cohort study, using the French national healthcare database, including all individuals ≥ 45 years old with a first delivery of oral ATs between 1 January 2013 and 31 December 2017. The cumulative incidence of oral AT combinations was estimated with the Fine and Gray method, taking into account the competitive risk of death. We compared the cumulative incidence of major bleeding according to the type of oral AT treatment initiated at study entry (monotherapy or oral AT combinations). During the study period, 22,220 individuals were included (mean (SD) age 68 (12) years). The cumulative incidence of oral AT combinations at 5 years was 27.8% (95% confidence interval (CI) 26.8-28.9). Overall, 64% of any oral AT combinations did not comply with guidelines. The cumulative incidence of major bleeding and death in the whole cohort at 5 years was 4.1% (95% CI 3.7-4.6) and 10.8% (95% CI 10.1-11.6), respectively. Risk of major bleeding increased among individuals with oral AT combinations versus oral AT monotherapy at study entry (subdistribution hazard ratio sHR: 2.16 (1.01-4.63)); with no difference in terms of death. The use of oral AT combinations among oral AT users is frequent, often inappropriately prescribed, and associated with an increased risk of major bleeding.

Keywords: adverse drug event; antithrombotic combinations; hemorrhage; inappropriate prescribing; vascular diseases.

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Conflict of interest statement

All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (accessed date 30 March 2021) and declare (except JPC): no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. JP Collet has received research grants from Bristol-Myers Squibb, Medtronic, and lecture fees from Lead-Up, WebMD, AstraZeneca, Bayer (<10 KE) outside the submitted work.

Figures

Figure 1
Figure 1
Flow chart. Abbreviations: EGB: échantillon généraliste des bénéficiaires (general sample of beneficiaries); AT: antithrombotics
Figure 2
Figure 2
Cumulative incidence curves of oral antithrombotic (AT) combination and death for the whole cohort (n = 22,220), over the 5-year study.
Figure 3
Figure 3
Proportion of inappropriate oral antithrombotic combination. Abbreviations: AT: antithrombotics; DOA: direct oral anticoagulant; VKA: vitamin K antagonist.
See this image and copyright information in PMC

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