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Canadian Journal of Cardiology

Time in Therapeutic Range With Vitamin K Antagonists in Congenital Heart Disease: A Multicentre Study

Published:August 11, 2022DOI:https://doi.org/10.1016/j.cjca.2022.08.004

      Abstract

      Background

      Vitamin K antagonists (VKAs) are frequently prescribed to patients with congenital heart disease (CHD) for atrial arrhythmias or Fontan palliation, but there is a paucity of data regarding time spent in the therapeutic range (TTR). We sought to determine the TTR in patients with CHD and atrial arrhythmias or Fontan palliation prescribed VKAs and explore associations with thromboembolic and bleeding events.

      Methods

      A multicentre North American cohort study was conducted on patients with CHD who received VKAs for sustained atrial arrhythmia or Fontan palliation. TTR was calculated using the Rosendaal linear interpolation method. Generalized estimating equations were used to explore factors associated with time outside the therapeutic range.

      Results

      A total of 567 patients, aged 33 ± 17 years, 56% female, received VKAs for 11.5 ± 8.4 years for atrial arrhythmias (63.0%) or Fontan palliation (58.0%). CHD was simple, moderate, and complex in 10.8%, 20.3%, and 69.0%, respectively. Site investigators perceived good control over international normalized ratio (INR) levels in most patients (75.3%), with no or minor compliance or adherence issues (85.6%). The mean TTR was 41.9% (95% confidence interval [CI], 39.0%-44.8%). Forty-seven (8.3%) and 34 (6.0%) patients had thromboembolic and bleeding events, respectively. Thromboembolic events were associated with a higher proportion of time below the therapeutic range (31.3% vs 19.1%, P = 0.003) and bleeding complications with a higher proportion of time above the therapeutic range (32.5% vs 19.5%, P = 0.006).

      Conclusions

      Patients with CHD who receive VKAs spend < 42% of their time with INR levels in the therapeutic range, with repercussions regarding thromboembolic and bleeding complications.

      Résumé

      Contexte

      Les antagonistes de la vitamine K (AVK) sont souvent prescrits aux patients atteints d’une cardiopathie congénitale et présentant une arythmie auriculaire ou une circulation de Fontan, mais il existe peu de données quant au temps passé dans la marge thérapeutique. Nous avons tenté de déterminer le temps passé dans la marge thérapeutique chez ces patients sous AVK et nous avons exploré les associations avec la thromboembolie et l’hémorragie.

      Méthodologie

      Une étude de cohorte multicentrique a été menée en Amérique du Nord auprès de patients qui étaient atteints d’une cardiopathie congénitale et qui prenaient des AVK pour une arythmie auriculaire soutenue ou une circulation de Fontan. Le temps passé dans la marge thérapeutique a été calculé à l’aide de la méthode d’interpolation linéaire de Rosendaal. Des équations d’estimation généralisées ont été utilisées pour explorer les facteurs associés au temps passé en dehors de la marge thérapeutique.

      Résultats

      Au total, 567 patients, dont 56 % de femmes, âgés en moyenne de 33 ans ± 17 ans, ont reçu des AVK pendant 11,5 ans ± 8,4 ans pour une arythmie auriculaire (63,0 %) ou une circulation de Fontan (58,0 %). Les cardiopathies congénitales étaient simples, modérées ou complexes dans une proportion de 10,8 %, de 20,3 % et de 69,0 %, respectivement. Les chercheurs du centre ont noté une bonne maîtrise du rapport international normalisé (RIN) chez la plupart des patients (75,3 %) avec aucun ou peu de problèmes d’adhésion au traitement (85,6 %). Le temps moyen passé dans la marge thérapeutique était de 41,9 % (intervalle de confiance [IC] à 95 % : de 39,0 % à 44,8 %). En tout, 47 patients (8,3 %) et 34 patients (6,0 %) ont présenté une thromboembolie et une hémorragie, respectivement. La thromboembolie était associée à une plus grande proportion de temps passé sous la marge thérapeutique (31,3 % vs 19,1 %; p = 0,003), et les complications hémorragiques, à une plus forte proportion de temps passé au-dessus de la marge thérapeutique (32,5 % vs 19,5 %; p = 0,006).

      Conclusions

      Les patients atteints de cardiopathies congénitales qui reçoivent des AVK passent < 42 % de leur temps dans la marge thérapeutique du RIN, ce qui s’accompagne de complications, comme la thromboembolie et l’hémorragie.

      Graphical abstract

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