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Challenging the FDA Black Box Warning for High Aspirin Dose With Ticagrelor in Patients With Diabetes

Ticagrelor, a novel reversible antiplatelet agent, has a Food and Drug Administration (FDA) black box warning to avoid maintenance doses of aspirin (ASA) >100 mg/daily. This restriction is based on the hypothesis that ASA doses >100 mg somehow decreased ticagrelor’s benefit in the Platelet Inh...

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Autores principales: DiNicolantonio, James J., Serebruany, Victor L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581224/
https://www.ncbi.nlm.nih.gov/pubmed/23431005
http://dx.doi.org/10.2337/db12-0746
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author DiNicolantonio, James J.
Serebruany, Victor L.
author_facet DiNicolantonio, James J.
Serebruany, Victor L.
author_sort DiNicolantonio, James J.
collection PubMed
description Ticagrelor, a novel reversible antiplatelet agent, has a Food and Drug Administration (FDA) black box warning to avoid maintenance doses of aspirin (ASA) >100 mg/daily. This restriction is based on the hypothesis that ASA doses >100 mg somehow decreased ticagrelor’s benefit in the Platelet Inhibition and Patient Outcomes (PLATO) U.S. cohort. However, these data are highly postrandomized, come from a very small subgroup in PLATO (57% of patients in the U.S. site), and make no biological sense. Moreover, the ticagrelor-ASA interaction was not significant by any multivariate Cox regression analyses. The Complete Response Review for ticagrelor indicates that for U.S. PLATO patients, an ASA dose >300 mg was not a significant interaction for vascular outcomes. In the ticagrelor-ASA >300 mg cohort, all-cause and vascular mortality were not significantly increased (hazard ratio [HR] 1.27 [95% CI 0.84–1.93], P = 0.262 and 1.39 [0.87–2.2], P = 0.170), respectively. Furthermore, for major adverse cardiovascular events (MACEs), 30-day all-cause mortality, and 30-day vascular mortality, the strongest interaction is the diabetes-ASA interaction. That is, patients who had diabetes had significantly fewer MACEs through study end (0.49 [0.34–0.63], P < 0.0001), significantly less 30-day all-cause mortality (0.33 [0.20–0.56], P < 0.0001), and significantly less 30-day vascular mortality (0.35 [0.22–0.55], P < 0.0001), respectively, when given high-dose (300–325 mg) ASA, regardless of treatment (clopidogrel or ticagrelor) assignment. The black box warning for the use of maintenance ASA doses >100 mg with ticagrelor is inappropriate for patients with diabetes and not evidence based.
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spelling pubmed-35812242014-03-01 Challenging the FDA Black Box Warning for High Aspirin Dose With Ticagrelor in Patients With Diabetes DiNicolantonio, James J. Serebruany, Victor L. Diabetes Perspectives In Diabetes Ticagrelor, a novel reversible antiplatelet agent, has a Food and Drug Administration (FDA) black box warning to avoid maintenance doses of aspirin (ASA) >100 mg/daily. This restriction is based on the hypothesis that ASA doses >100 mg somehow decreased ticagrelor’s benefit in the Platelet Inhibition and Patient Outcomes (PLATO) U.S. cohort. However, these data are highly postrandomized, come from a very small subgroup in PLATO (57% of patients in the U.S. site), and make no biological sense. Moreover, the ticagrelor-ASA interaction was not significant by any multivariate Cox regression analyses. The Complete Response Review for ticagrelor indicates that for U.S. PLATO patients, an ASA dose >300 mg was not a significant interaction for vascular outcomes. In the ticagrelor-ASA >300 mg cohort, all-cause and vascular mortality were not significantly increased (hazard ratio [HR] 1.27 [95% CI 0.84–1.93], P = 0.262 and 1.39 [0.87–2.2], P = 0.170), respectively. Furthermore, for major adverse cardiovascular events (MACEs), 30-day all-cause mortality, and 30-day vascular mortality, the strongest interaction is the diabetes-ASA interaction. That is, patients who had diabetes had significantly fewer MACEs through study end (0.49 [0.34–0.63], P < 0.0001), significantly less 30-day all-cause mortality (0.33 [0.20–0.56], P < 0.0001), and significantly less 30-day vascular mortality (0.35 [0.22–0.55], P < 0.0001), respectively, when given high-dose (300–325 mg) ASA, regardless of treatment (clopidogrel or ticagrelor) assignment. The black box warning for the use of maintenance ASA doses >100 mg with ticagrelor is inappropriate for patients with diabetes and not evidence based. American Diabetes Association 2013-03 2013-02-14 /pmc/articles/PMC3581224/ /pubmed/23431005 http://dx.doi.org/10.2337/db12-0746 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Perspectives In Diabetes
DiNicolantonio, James J.
Serebruany, Victor L.
Challenging the FDA Black Box Warning for High Aspirin Dose With Ticagrelor in Patients With Diabetes
title Challenging the FDA Black Box Warning for High Aspirin Dose With Ticagrelor in Patients With Diabetes
title_full Challenging the FDA Black Box Warning for High Aspirin Dose With Ticagrelor in Patients With Diabetes
title_fullStr Challenging the FDA Black Box Warning for High Aspirin Dose With Ticagrelor in Patients With Diabetes
title_full_unstemmed Challenging the FDA Black Box Warning for High Aspirin Dose With Ticagrelor in Patients With Diabetes
title_short Challenging the FDA Black Box Warning for High Aspirin Dose With Ticagrelor in Patients With Diabetes
title_sort challenging the fda black box warning for high aspirin dose with ticagrelor in patients with diabetes
topic Perspectives In Diabetes
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581224/
https://www.ncbi.nlm.nih.gov/pubmed/23431005
http://dx.doi.org/10.2337/db12-0746
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