Refuting the ticagrelor-aspirin black box warning: And proposing a ticagrelor early-PCI black box warning

James J. Dinicolantonio, Victor L. Serebruany, Ales Tomek

Research output: Contribution to journalArticle

Abstract

Context Ticagrelor, a novel reversible antiplatelet agent, has a black box warning to avoid maintenance doses of aspirin > 100 mg. However, a significant ticagrelor-early percutaneous coronary intervention (PCI) interaction exists. Objective To discuss the inappropriateness of the black box warning for aspirin doses > 100 mg with ticagrelor and the appropriateness (and need) for a black box warning for ticagrelor patients needing early (within 24 hours of randomization) PCI. Results The FDA Complete Response Review for ticagrelor indicates that aspirin doses ≥ 300 mg/daily was not a significant interaction. In the ticagrelor-aspirin ≥ 300 mg cohort, all-cause mortality (through study end) and cardiovascular (CV) mortality (through study end) were not significantly increased (HR = 1.27; 95% CI, 0.84-1.93, p = 0.262 and HR = 1.39; 95% CI:0.87-2.2, p = 0.170), respectively. However, in patients treated with early (within 24 hours) PCI, ticagrelor significantly increased all-cause mortality (30 day: HR = 1.89; 95% CI: 1.26-2.81, p = 0.002, and through study end, HR = 1.41; 95% CI,1.08-1.84, p = 0.012) and increased CV mortality (30 day: HR = 1.31; 95% CI: 0.97-1.77, p = 0.075, and through study end, HR = 1.35; 95% CI, 0.995-1.82, p = 0.054) compared to clopidogrel. Conclusions Early-PCI was more prevalent in the US versus outside-US regions (61% versus 49%). The black box warning for the use of maintenance aspirin doses over 100 mg/daily with ticagrelor is inappropriate and ignores the more important, credible, and highly significant ticagrelor-early PCI adverse interaction in PLATO.

Original languageEnglish (US)
Pages (from-to)1721-1723
Number of pages3
JournalInternational Journal of Cardiology
Volume168
Issue number3
DOIs
StatePublished - Oct 3 2013

Fingerprint

Drug Labeling
Percutaneous Coronary Intervention
Aspirin
Mortality
clopidogrel
Ticagrelor
Platelet Aggregation Inhibitors
Random Allocation
Maintenance

Keywords

  • Clinical Trials
  • Clopidogrel
  • Percutaneous Coronary Interventions
  • Ticagrelor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Refuting the ticagrelor-aspirin black box warning : And proposing a ticagrelor early-PCI black box warning. / Dinicolantonio, James J.; Serebruany, Victor L.; Tomek, Ales.

In: International Journal of Cardiology, Vol. 168, No. 3, 03.10.2013, p. 1721-1723.

Research output: Contribution to journalArticle

Dinicolantonio, James J. ; Serebruany, Victor L. ; Tomek, Ales. / Refuting the ticagrelor-aspirin black box warning : And proposing a ticagrelor early-PCI black box warning. In: International Journal of Cardiology. 2013 ; Vol. 168, No. 3. pp. 1721-1723.
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abstract = "Context Ticagrelor, a novel reversible antiplatelet agent, has a black box warning to avoid maintenance doses of aspirin > 100 mg. However, a significant ticagrelor-early percutaneous coronary intervention (PCI) interaction exists. Objective To discuss the inappropriateness of the black box warning for aspirin doses > 100 mg with ticagrelor and the appropriateness (and need) for a black box warning for ticagrelor patients needing early (within 24 hours of randomization) PCI. Results The FDA Complete Response Review for ticagrelor indicates that aspirin doses ≥ 300 mg/daily was not a significant interaction. In the ticagrelor-aspirin ≥ 300 mg cohort, all-cause mortality (through study end) and cardiovascular (CV) mortality (through study end) were not significantly increased (HR = 1.27; 95{\%} CI, 0.84-1.93, p = 0.262 and HR = 1.39; 95{\%} CI:0.87-2.2, p = 0.170), respectively. However, in patients treated with early (within 24 hours) PCI, ticagrelor significantly increased all-cause mortality (30 day: HR = 1.89; 95{\%} CI: 1.26-2.81, p = 0.002, and through study end, HR = 1.41; 95{\%} CI,1.08-1.84, p = 0.012) and increased CV mortality (30 day: HR = 1.31; 95{\%} CI: 0.97-1.77, p = 0.075, and through study end, HR = 1.35; 95{\%} CI, 0.995-1.82, p = 0.054) compared to clopidogrel. Conclusions Early-PCI was more prevalent in the US versus outside-US regions (61{\%} versus 49{\%}). The black box warning for the use of maintenance aspirin doses over 100 mg/daily with ticagrelor is inappropriate and ignores the more important, credible, and highly significant ticagrelor-early PCI adverse interaction in PLATO.",
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N2 - Context Ticagrelor, a novel reversible antiplatelet agent, has a black box warning to avoid maintenance doses of aspirin > 100 mg. However, a significant ticagrelor-early percutaneous coronary intervention (PCI) interaction exists. Objective To discuss the inappropriateness of the black box warning for aspirin doses > 100 mg with ticagrelor and the appropriateness (and need) for a black box warning for ticagrelor patients needing early (within 24 hours of randomization) PCI. Results The FDA Complete Response Review for ticagrelor indicates that aspirin doses ≥ 300 mg/daily was not a significant interaction. In the ticagrelor-aspirin ≥ 300 mg cohort, all-cause mortality (through study end) and cardiovascular (CV) mortality (through study end) were not significantly increased (HR = 1.27; 95% CI, 0.84-1.93, p = 0.262 and HR = 1.39; 95% CI:0.87-2.2, p = 0.170), respectively. However, in patients treated with early (within 24 hours) PCI, ticagrelor significantly increased all-cause mortality (30 day: HR = 1.89; 95% CI: 1.26-2.81, p = 0.002, and through study end, HR = 1.41; 95% CI,1.08-1.84, p = 0.012) and increased CV mortality (30 day: HR = 1.31; 95% CI: 0.97-1.77, p = 0.075, and through study end, HR = 1.35; 95% CI, 0.995-1.82, p = 0.054) compared to clopidogrel. Conclusions Early-PCI was more prevalent in the US versus outside-US regions (61% versus 49%). The black box warning for the use of maintenance aspirin doses over 100 mg/daily with ticagrelor is inappropriate and ignores the more important, credible, and highly significant ticagrelor-early PCI adverse interaction in PLATO.

AB - Context Ticagrelor, a novel reversible antiplatelet agent, has a black box warning to avoid maintenance doses of aspirin > 100 mg. However, a significant ticagrelor-early percutaneous coronary intervention (PCI) interaction exists. Objective To discuss the inappropriateness of the black box warning for aspirin doses > 100 mg with ticagrelor and the appropriateness (and need) for a black box warning for ticagrelor patients needing early (within 24 hours of randomization) PCI. Results The FDA Complete Response Review for ticagrelor indicates that aspirin doses ≥ 300 mg/daily was not a significant interaction. In the ticagrelor-aspirin ≥ 300 mg cohort, all-cause mortality (through study end) and cardiovascular (CV) mortality (through study end) were not significantly increased (HR = 1.27; 95% CI, 0.84-1.93, p = 0.262 and HR = 1.39; 95% CI:0.87-2.2, p = 0.170), respectively. However, in patients treated with early (within 24 hours) PCI, ticagrelor significantly increased all-cause mortality (30 day: HR = 1.89; 95% CI: 1.26-2.81, p = 0.002, and through study end, HR = 1.41; 95% CI,1.08-1.84, p = 0.012) and increased CV mortality (30 day: HR = 1.31; 95% CI: 0.97-1.77, p = 0.075, and through study end, HR = 1.35; 95% CI, 0.995-1.82, p = 0.054) compared to clopidogrel. Conclusions Early-PCI was more prevalent in the US versus outside-US regions (61% versus 49%). The black box warning for the use of maintenance aspirin doses over 100 mg/daily with ticagrelor is inappropriate and ignores the more important, credible, and highly significant ticagrelor-early PCI adverse interaction in PLATO.

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