Cangrelor Induces More Potent Platelet Inhibition without Increasing Bleeding in Resuscitated Patients

Florian Prüller, Lukasz Bis, Oliver Leopold Milke, Friedrich Fruhwald, Sascha Pätzold, Siegfried Altmanninger-Sock, Jolanta Siller-Matula, Friederike von Lewinski, Klemens Ablasser, Michael Sacherer, Dirk von Lewinski, Florian Prüller, Lukasz Bis, Oliver Leopold Milke, Friedrich Fruhwald, Sascha Pätzold, Siegfried Altmanninger-Sock, Jolanta Siller-Matula, Friederike von Lewinski, Klemens Ablasser, Michael Sacherer, Dirk von Lewinski

Abstract

Dual antiplatelet therapy is the standard of care for patients with myocardial infarction (MI), who have been resuscitated and treated with therapeutic hypothermia (TH). We compare the antiplatelet effect and bleeding risk of intravenous cangrelor to oral P2Y12-inhibitors in patients with MI receiving TH in a prospective comparison of two matched patient cohorts. Twenty-five patients within the CANGRELOR cohort were compared to 17 patients receiving oral P2Y12-inhibitors. CANGRELOR group (NCT03445546) and the ORAL P2Y12 Group (NCT02914795) were registered at clinicaltrials.gov. Platelet function testing was performed using light-transmittance aggregometry and monitored for 4 days. P2Y12-inhibition was stronger in CANGRELOR compared to ORAL P2Y12 (adenosine diphosphate (ADP) (area under the curve (AUC)) 26.0 (5.9⁻71.6) vs. 160.9 (47.1⁻193.7)) at day 1. This difference decreased over the following days as more patients were switched from CANGRELOR to oral P2Y12-inhibitor treatment. There was no difference in the effect of aspirin between the two groups. We did not observe significant differences with respect to thrombolysis in myocardial infarction (TIMI) or Bleeding Academic Research Consortium (BARC) classified bleedings, number of blood transfusions or drop in haemoglobin B (Hb) or hematocrit (Hct) over time. Cangrelor treatment is not only feasible and effective in resuscitated patients, but also inhibited platelet function more effectively than orally administered P2Y12-inhibitors without an increased event rate for bleeding.

Keywords: acute coronary syndrome; cangrelor; light transmission tomography; myocardial infarction; platelet function; resuscitation.

Conflict of interest statement

The authors declare that they have no competing interests with regard to any organization or entity with a financial interest in competition with the subject matter or materials discussed in this publication. DvL received advisory honorarias from AstraZeneca and DaichiSankyo marketing the oral drugs ticagrelor and prasugrel, respectively.

Figures

Figure 1
Figure 1
(A) Representative original recordings of aggregation curves in a patient on cangrelor treatment (left) and another patient on oral P2Y12-inhibitor treatment (right) Platelet activating compounds: collagen (blue), adenosine diphosphate (ADP) [black], arachidonic acid [red], and thrombin receptor activator peptide (green). (B) Median ADP AUC for the first 4 days showing significant difference on day 1. CANGRELOR (green) vs. ORAL-P2Y12 (blue).
Figure 2
Figure 2
(A) Median collagen AUC for the first 4 days. CANGRELOR (green) vs. ORAL-P2Y12 (blue). (B) Median collagen AUC for the 25 patients of the CANGRELOR group. Patients with intravenous ASS therapy (black) or oral therapy (gray) after day 1.
Figure 3
Figure 3
Correlation of SOFA score with ADP-AUC. Data of the 25 patients of the CANGRELOR group is shown. Day 1 (blue), day 2 (green), day 3 (orange), and day 4 (purple) had no differences. Overall data showed r = −0.076; p = 0.623).
Figure 4
Figure 4
(A) Median haemoglobin for the first 4 days after index event. CANGRELOR (green) vs. ORAL-P2Y12 (blue); (B) Median haematocrit for the first 4 days after index event. CANGRELOR (green) vs. ORAL-P2Y12 (blue).

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