Cangrelor infusion is associated with an increased risk for bleeding: Meta-analysis of randomized trials

Victor L. Serebruany, D. Aradi, Moo Hyun Kim, Dirk Sibbing

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Context Aggressive antiplatelet strategies unquestionably cause extra hemorrhagic risks. Bleeding episodes are associated with poor outcomes including increased mortality. However, lack of uniform reporting and adjudication of bleeding events might prevent objective evaluation of the efficacy/safety profile of antithrombotic agents. Objective We analyzed the bleeding rates by several previously used bleeding scales (TIMI, GUSTO, ACUITY, and BARC) after cangrelor in recent head-to-head randomized, controlled clinical trials (RCTs). Results Data for meta-analyses were pooled from 3 RCTs (CHAMPION-PLATFORM, CHAMPION-PCI and CHAMPION-PHOENIX) including 25,106 patients. In addition, the bleeding risks were also assessed from the small (n = 210) BRIDGE RCT. Cangrelor caused a significantly increased risk for major bleeding at 48 h according to the ACUITY scale (RR: 1.51, 95% CI: 1.32-1.72, p <0.00001); however, this impact was less prominent according to less sensitive bleeding scales (GUSTO severe: RR: 1.21, 95% CI: 0.70-2.11, p = 0.49; TIMI major: RR: 1.00, 95% CI: 0.59-1.68, p = 0.99). There was also an obvious trend towards an increased risk for any transfusions (RR: 1.31, 95% CI: 0.97-1.77, p = 0.08) and TIMI major + minor bleeding events (RR: 1.30, 95% CI: 0.96-1.76, p = 0.09). Conclusions Cangrelor on top of aspirin or/and clopidogrel increases the risk for early bleeding events after PCI; however, it largely depends on the bleeding definition used, and how this excess risk of bleeding was captured. The bleeding hazard needs to be verified in the ongoing FDA secondary cangrelor review.

Original languageEnglish
Pages (from-to)225-228
Number of pages4
JournalInternational Journal of Cardiology
Volume169
Issue number3
DOIs
Publication statusPublished - Nov 5 2013

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Meta-Analysis
Hemorrhage
Randomized Controlled Trials
clopidogrel
cangrelor
Fibrinolytic Agents
Aspirin
Safety
Mortality

Keywords

  • Bleeding
  • Cangrelor
  • Clinical trials
  • Safety

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Cangrelor infusion is associated with an increased risk for bleeding : Meta-analysis of randomized trials. / Serebruany, Victor L.; Aradi, D.; Kim, Moo Hyun; Sibbing, Dirk.

In: International Journal of Cardiology, Vol. 169, No. 3, 05.11.2013, p. 225-228.

Research output: Contribution to journalArticle

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abstract = "Context Aggressive antiplatelet strategies unquestionably cause extra hemorrhagic risks. Bleeding episodes are associated with poor outcomes including increased mortality. However, lack of uniform reporting and adjudication of bleeding events might prevent objective evaluation of the efficacy/safety profile of antithrombotic agents. Objective We analyzed the bleeding rates by several previously used bleeding scales (TIMI, GUSTO, ACUITY, and BARC) after cangrelor in recent head-to-head randomized, controlled clinical trials (RCTs). Results Data for meta-analyses were pooled from 3 RCTs (CHAMPION-PLATFORM, CHAMPION-PCI and CHAMPION-PHOENIX) including 25,106 patients. In addition, the bleeding risks were also assessed from the small (n = 210) BRIDGE RCT. Cangrelor caused a significantly increased risk for major bleeding at 48 h according to the ACUITY scale (RR: 1.51, 95{\%} CI: 1.32-1.72, p <0.00001); however, this impact was less prominent according to less sensitive bleeding scales (GUSTO severe: RR: 1.21, 95{\%} CI: 0.70-2.11, p = 0.49; TIMI major: RR: 1.00, 95{\%} CI: 0.59-1.68, p = 0.99). There was also an obvious trend towards an increased risk for any transfusions (RR: 1.31, 95{\%} CI: 0.97-1.77, p = 0.08) and TIMI major + minor bleeding events (RR: 1.30, 95{\%} CI: 0.96-1.76, p = 0.09). Conclusions Cangrelor on top of aspirin or/and clopidogrel increases the risk for early bleeding events after PCI; however, it largely depends on the bleeding definition used, and how this excess risk of bleeding was captured. The bleeding hazard needs to be verified in the ongoing FDA secondary cangrelor review.",
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N2 - Context Aggressive antiplatelet strategies unquestionably cause extra hemorrhagic risks. Bleeding episodes are associated with poor outcomes including increased mortality. However, lack of uniform reporting and adjudication of bleeding events might prevent objective evaluation of the efficacy/safety profile of antithrombotic agents. Objective We analyzed the bleeding rates by several previously used bleeding scales (TIMI, GUSTO, ACUITY, and BARC) after cangrelor in recent head-to-head randomized, controlled clinical trials (RCTs). Results Data for meta-analyses were pooled from 3 RCTs (CHAMPION-PLATFORM, CHAMPION-PCI and CHAMPION-PHOENIX) including 25,106 patients. In addition, the bleeding risks were also assessed from the small (n = 210) BRIDGE RCT. Cangrelor caused a significantly increased risk for major bleeding at 48 h according to the ACUITY scale (RR: 1.51, 95% CI: 1.32-1.72, p <0.00001); however, this impact was less prominent according to less sensitive bleeding scales (GUSTO severe: RR: 1.21, 95% CI: 0.70-2.11, p = 0.49; TIMI major: RR: 1.00, 95% CI: 0.59-1.68, p = 0.99). There was also an obvious trend towards an increased risk for any transfusions (RR: 1.31, 95% CI: 0.97-1.77, p = 0.08) and TIMI major + minor bleeding events (RR: 1.30, 95% CI: 0.96-1.76, p = 0.09). Conclusions Cangrelor on top of aspirin or/and clopidogrel increases the risk for early bleeding events after PCI; however, it largely depends on the bleeding definition used, and how this excess risk of bleeding was captured. The bleeding hazard needs to be verified in the ongoing FDA secondary cangrelor review.

AB - Context Aggressive antiplatelet strategies unquestionably cause extra hemorrhagic risks. Bleeding episodes are associated with poor outcomes including increased mortality. However, lack of uniform reporting and adjudication of bleeding events might prevent objective evaluation of the efficacy/safety profile of antithrombotic agents. Objective We analyzed the bleeding rates by several previously used bleeding scales (TIMI, GUSTO, ACUITY, and BARC) after cangrelor in recent head-to-head randomized, controlled clinical trials (RCTs). Results Data for meta-analyses were pooled from 3 RCTs (CHAMPION-PLATFORM, CHAMPION-PCI and CHAMPION-PHOENIX) including 25,106 patients. In addition, the bleeding risks were also assessed from the small (n = 210) BRIDGE RCT. Cangrelor caused a significantly increased risk for major bleeding at 48 h according to the ACUITY scale (RR: 1.51, 95% CI: 1.32-1.72, p <0.00001); however, this impact was less prominent according to less sensitive bleeding scales (GUSTO severe: RR: 1.21, 95% CI: 0.70-2.11, p = 0.49; TIMI major: RR: 1.00, 95% CI: 0.59-1.68, p = 0.99). There was also an obvious trend towards an increased risk for any transfusions (RR: 1.31, 95% CI: 0.97-1.77, p = 0.08) and TIMI major + minor bleeding events (RR: 1.30, 95% CI: 0.96-1.76, p = 0.09). Conclusions Cangrelor on top of aspirin or/and clopidogrel increases the risk for early bleeding events after PCI; however, it largely depends on the bleeding definition used, and how this excess risk of bleeding was captured. The bleeding hazard needs to be verified in the ongoing FDA secondary cangrelor review.

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