Pharmacodynamic Effects During聽the聽Transition Between Cangrelor聽and Ticagrelor

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• 作者：David J. Schneider ; MD ; ^{david.schneider@uvm.edu" class="auth_mail} ; Zubin Agarwal ; MD ; Naveen Seecheran ; MD ; Friederike K. Keating ; MD ; Prospero Gogo ; MD
• 关键词：antiplatelet ; cangrelor ; pharmacodynamics ; ticagrelor ; transition
• 刊名：JACC: Cardiovascular Interventions
• 出版年：April, 2014
• 年：2014
• 卷：7
• 期：4
• 页码：435-442
• 全文大小：641 K

文摘

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Objectives

This study sought to determine pharmacodynamic effects during transition from intravenous cangrelor to oral ticagrelor and from oral ticagrelor to intravenous cangrelor.

Background

Cangrelor is an intravenous antagonist of P2Yb>12b> and its use will require transition to and from oral agents.

Methods

Patients (n聽= 12) with stable coronary artery disease who were taking aspirin 81 mg daily were recruited. On study day 1, they received a bolus plus 2-h infusion of cangrelor plus a 180-mg dose of ticagrelor at either 0.5 h (n聽= 6) or 1.25 h (n聽= 6). Pharmacodynamic effects (light transmission platelet aggregation in response to 20 and 5 渭mol/l adenosine diphosphate, VerifyNow, P2Yb>12b> assay (Accumetrics, San Diego, California), vasodilator-stimulated phosphoprotein index, and flow cytometry) were assessed during and after the cangrelor infusion. Patients took 90 mg of ticagrelor twice daily for either 6 (n聽= 6) or 7 (n聽= 6) doses. On study day 5, pharmacodynamic effects聽were assessed before and during a bolus plus 2-h infusion of cangrelor.

Results

During cangrelor infusion, extensive inhibition of platelet function reflected by limited residual platelet reactivity was apparent. After cangrelor was stopped, the antiplatelet effects of ticagrelor were preserved despite a modest increase in platelet reactivity.

Conclusions

Ticagrelor given before or during infusion of cangrelor did not attenuate the pharmacodynamic effects of cangrelor. The pharmacodynamic effects of ticagrelor were preserved when ticagrelor was given during infusion of cangrelor. Consistent with the reversible binding of ticagrelor, this oral P2Yb>12b> antagonist can be administered before, during, or after treatment with cangrelor.