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Thrombolysis Outcomes in Patients with Diabetes and Previous Stroke: A Meta-Analysis

  • Azalea T. Pajo (a1), Jose Danilo B. Diestro (a2), Adrian I. Espiritu (a1) (a3), Adam A. Dmytriw (a4), Alejandro Enriquez-Marulanda (a5), Robert Joseph C. Sarmiento (a1), Marjorie Anne C. Bagnas (a1), Julian Spears (a6) and Maria Cristina Z. San Jose (a1)...

Abstract:

Background:

Intravenous tissue-type plasminogen activator (IVtPA) is a proven treatment for acute ischemic stroke; however, diabetes mellitus (DM) and previous cerebral infarction (PCI) were considered relative contraindications for thrombolysis within the 3–4.5 h period.

Objective:

The study aimed to determine the safety and efficacy of IVtPA among diabetic patients with PCI presenting with acute ischemic stroke.

Methods:

Studies which evaluated the outcome of IVtPA in terms of symptomatic intracerebral hemorrhage (sICH), functional outcome in modified Rankin scale, and death among diabetic patients with PCI presenting with acute ischemic stroke within the 3–4.5 h period were systematically searched until July 2019. Screening and eligibility criteria were applied. Risk of bias was evaluated using the Newcastle–Ottawa Scale. Odds ratios (ORs) with 95% confidence interval (CI) were used to compare measures of treatment effect. Mantel–Haenszel method and random-effects model were also employed.

Results:

Four registry-based studies with a total of 44,572 patients were included for quantitative synthesis. Giving IVtPA among DM+/PCI+ patients did not result in significantly increased rate of sICH (OR, 1.09; 95% CI, 0.88, 1.36) compared to No DM+/PCI+ patients. However, there was significantly higher mortality (OR, 1.81; 95% CI, 1.60, 2.06) in the DM+/PCI+ group. Conversely, among those who survived, the DM+/PCI+ patients were more functionally independent at 3 months (OR, 0.76; 95% CI, 0.61, 0.94).

Conclusion:

Limited evidence suggests that thrombolysis in DM+/PCI+ patients does not result in significantly higher incidence of sICH and may improve functional independence. However, the significantly higher mortality in this group warrants an assessment of the individualized risk–benefit ratio in the use of IVtPA.

RÉSUMÉ:

Méta-analyse des résultats d’un traitement thrombolytique administré à des patients diabétiques ayant des antécédents d’infarctus cérébraux.

Contexte :

L’altéplase par voie intraveineuse (tPA-IV) est un traitement pour les AVC ischémiques aigus qui a fait ses preuves. Cela dit, le fait de souffrir de diabète sucré (DS) et d’avoir été victime dans le passé d’un infarctus cérébral continuent, dans des délais allant de 3 à 4,5 heures, à être considérés comme des contre-indications relatives pour un traitement thrombolytique.

Objectif :

Cette étude a cherché à démontrer la sécurité et l’efficacité du tPA-IV chez des patients diabétiques avec des antécédents d’infarctus cérébraux victimes d’un AVC ischémique aigu.

Méthodes :

Pour les patients décrits précédemment et tenant compte de délais de 3 à 4,5 heures, nous avons effectué une recherche systématique au sujet d’études évaluant l’efficacité du tPA-IV en lien avec de potentielles manifestations d’hémorragie intracérébrale symptomatique, des résultats fonctionnels à l’échelle modifiée de Rankin et des taux de mortalité. En plus de nous limiter à des études parues avant juillet 2019, nous avons mis de l’avant des critères de filtrage et d’admissibilité. Les risques de biais ont été évalués au moyen de l’échelle de Newcastle-Ottawa. Les rapports des cotes (RC) avec un intervalle de confiance (IC) de 95 % ont été par ailleurs utilisés pour comparer entre elles les mesures de l’effet du traitement. Finalement, la méthode de Mantel-Haenszel ainsi qu’un modèle à effets aléatoires ont été également appelés en renfort.

Résultats :

Au total, 4 études portant sur 44 572 dossiers de patients ont été inclues en vue d’une synthèse quantitative. Le fait d’administrer du tPA-IV aux patients décrits ci-dessus n’a pas entraîné une augmentation significative du taux d’hémorragie intracérébrale symptomatique (RC 1,09 ; IC 95 % : 0,88 - 1,36) en comparaison avec des patients non-diabétiques n’ayant pas d’antécédents d’infarctus cérébraux. Toutefois, les taux de mortalité se sont avérés nettement plus élevés (RC 1,81 ; IC 95 % : 1,60 - 2,06) parmi les patients qui nous intéressent ici. à l’inverse, parmi les patients ayant survécu, ceux qui avaient des antécédents d’infarctus cérébraux et qui étaient diabétiques se sont révélés au bout de 3 mois plus autonomes sur le plan fonctionnel (RC 0,76 ; IC 95 % : 0,61- 0,94).

Conclusion :

Pour l’instant, des preuves limitées suggèrent qu’un traitement thrombolytique chez des patients diabétiques ayant des antécédents d’infarctus cérébraux n’entraîne pas une fréquence significativement plus élevée d’hémorragie intracérébrale symptomatique et pourrait améliorer en bout de ligne l’autonomie fonctionnelle des patients. Cela dit, le taux de mortalité nettement plus élevé au sein de ce groupe de patients justifie une évaluation du rapport risque-bénéfice individualisé rattaché au tPA-IV.

Copyright

Corresponding author

Correspondence to: Azalea T. Pajo, Department of Neurosciences, College of Medicine and Philippine General Hospital, University of the Philippines Manila, Taft Avenue, Ermita, Manila1000, Philippines. Email: atpajo@up.edu.ph or azaleapajo@gmail.com

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Thrombolysis Outcomes in Patients with Diabetes and Previous Stroke: A Meta-Analysis

  • Azalea T. Pajo (a1), Jose Danilo B. Diestro (a2), Adrian I. Espiritu (a1) (a3), Adam A. Dmytriw (a4), Alejandro Enriquez-Marulanda (a5), Robert Joseph C. Sarmiento (a1), Marjorie Anne C. Bagnas (a1), Julian Spears (a6) and Maria Cristina Z. San Jose (a1)...

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