Cangrelor infusion is associated with an increased risk for bleeding: meta-analysis of randomized trials.
BACKGROUND
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.
HeartDrug™ Research Laboratories, Johns Hopkins University, Osler Medical Building, 7600 Osler Drive, Suite 307, Towson, MD 21204, United States. Electronic address: heartdrug@aol.com.
Victor L
VL
Serebruany
Daniel
D
Aradi
Moo Hyun
MH
Kim
Dirk
D
Sibbing
D000249:Adenosine Monophosphate / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006470:Hemorrhage / Q000139:chemically induced* / Q000175:diagnosis* / Q000453:epidemiology; D006801:Humans; D007262:Infusions, Intravenous; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D012307:Risk Factors
D058921:Purinergic P2Y Receptor Antagonists; D000249:Adenosine Monophosphate; C117446:cangrelor
Bleeding; Cangrelor; Clinical trials; Safety