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

Benoît Guillet, Guillaume Cayla, Aurélien Lebreton, Nathalie Trillot, Bénédicte Wibaut, Céline Falaise, Sabine Castet, Philippe Gautier, Ségolène Claeyssens, Jean-François Schved, Benoît Guillet, Guillaume Cayla, Aurélien Lebreton, Nathalie Trillot, Bénédicte Wibaut, Céline Falaise, Sabine Castet, Philippe Gautier, Ségolène Claeyssens, Jean-François Schved

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.

Conflict of interest statement

None declared.

The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Figures

Fig. 1
Fig. 1
Description of patients and controls included in the COCHE study. (A) COCHE study flow chart. (B) Changes in antithrombotic treatments during the 2-year follow-up. AC, anticoagulant drug alone; ASA, aspirin; CABG, coronary artery bypass grafting; Clopi, clopidogrel; DAPT, dual antiplatelet therapy; DAPT + one anticoagulant drug; DES, drug-eluting stent; DOA, direct oral anticoagulant; DPT, dual pathway therapy (antiplatelet + anticoagulant); HA, hemophilia A; HB, hemophilia B; mod, moderate; PCI, percutaneous coronary intervention; SAPT, single antiplatelet therapy; sev, severe; TT, triple therapy; VKA, vitamin K antagonist.
Fig. 2
Fig. 2
Major bleeding-free survival curves for the COCHE and control groups. (A) In all patients. (B) In function of hemophilia severity.
Fig. 3
Fig. 3
Major bleeding events in function of hemophilia severity and basal clotting factor level. (A) Percentage of patients who reported at least one major bleeding episode during the 2-year follow-up period. (B) Mean annualized bleeding rate. CF: basal clotting factor; ABR: annualized bleeding rate.
Fig. 4
Fig. 4
Cardiovascular event-free survival curves for the COCHE and control groups.

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