Thromb Haemost
DOI: 10.1055/s-0040-1718410
Coagulation and Fibrinolysis

Long-Term Antithrombotic Treatments Prescribed for Cardiovascular Diseases in Patients with Hemophilia: Results from the French Registry

Benoît Guillet*
1  Centre Régional de Traitement des Maladies Hémorragiques, CHU de Rennes, et Université de Rennes 1, France
2  CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail), Univ Rennes, UMR_S 1085, Rennes, France
,
Guillaume Cayla*
3  Service de Cardiologie CHU de Nîmes, Université de Montpellier, Nimes, France
,
4  Centre Régional de Traitement des Hémophiles, CHU de Clermont-Ferrand, France
,
Nathalie Trillot
5  Centre Régional de Traitement des Hémophiles, CHU de Lille, France
,
Bénédicte Wibaut
5  Centre Régional de Traitement des Hémophiles, CHU de Lille, France
,
Céline Falaise
6  Centre Régional de Traitement des Hémophiles, CHU La Timone, Marseille, France
,
Sabine Castet
7  Centre Régional de Traitement des Hémophiles, CHU de Bordeaux, France
,
Philippe Gautier
8  Centre Régional de Traitement des Hémophiles, CHU de Caen, France
,
Ségolène Claeyssens
9  Centre Régional de Traitement des Hémophiles, CHU de Toulouse, France
,
Jean-François Schved
10  Centre Régional de Traitement des Hémophiles, Hôpital Saint-Eloi, CHRU de Montpellier, Montpellier, France
› Author Affiliations
Funding The publication was sponsored by CSL Behring, France.

Abstract

Cardiovascular diseases (CVDs) are a major issue in aging patients with hemophilia (PWHs). Antithrombotic agents are widely used in the general population for CVD treatment, but this recommendation is not fully applicable to PWHs. To improve treatment strategies, a prospective case–control study (COCHE) that analyzed CVD management and follow-up (2 years/patient) in PWHs was performed in France from 2011 to 2018. In total, 68 PWHs (median age: 65 years [39–89]; 48 mild, 10 moderate, and 10 severe hemophilia) were included (n = 50 with acute coronary syndrome, n = 17 with atrial fibrillation, n = 1 with both). They were matched with 68 control PWHs without antithrombotic treatment. In our series, bleeding was significantly influenced by (1) hemophilia severity, with a mean annualized bleeding ratio significantly higher in COCHE patients than in controls with basal clotting factor level up to 20%, (2) antihemorrhagic regimen (on-demand vs. prophylaxis) in severe (hazard ratio [HR] = 16.69 [95% confidence interval, CI: 8.2–47.26]; p < 0.0001) and moderate hemophilia (HR = 42.43 [95% CI: 1.86–966.1]; p = 0.0028), (3) type of antithrombotic treatment in mild hemophilia, with a significantly higher risk of bleeding in COCHE patients than in controls for dual-pathway therapy (HR = 15.64 [95% CI: 1.57–115.8]; p = 0.019), anticoagulant drugs alone (HR = 9.91 [95% CI: 1.34–73.47]; p = 0.0248), dual antiplatelet therapy (HR = 5.31 [95% CI: 1.23–22.92]; p = 0.0252), and single antiplatelet therapy (HR = 3.76 [95% CI: 1.13–12.55]; p = 0.0313); and (4) HAS-BLED score ≥3 (odds ratio [OR] = 33 [95% CI: 1.43–761.2]; p = 0.0065). Gastrointestinal bleeding was also significantly higher in COCHE patients than in controls (OR = 15 [95% CI: 1.84–268]; p = 0.0141). The COCHE study confirmed that antithrombotic treatments in PWHs are associated with increased bleeding rates in function of hemophilia-specific factors and also of known factors in the general population.

Authors' Contributions

All authors contributed to the study concept and design. B.G., G.C., and J-F.S. recruited patients, analyzed and interpreted results, and wrote the manuscript. A.L., B.W., C.F., S.C., P.G., and S.C. recruited patients.


* Benoît Guillet and Guillaume Cayla contributed equally to the present work.


Supplementary Material



Publication History

Received: 10 June 2019

Accepted: 28 August 2020

Publication Date:
24 October 2020 (online)

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