Experts Debate Optimal Pharmacologic Approach for STEMI Patients
At TCT 2015, three physicians made cases for and against the use of cangrelor, prasugrel or ticagrelor for patients with STEMI undergoing PCI.
Harvey D. White, DSc, of Auckland City Hospital, New Zealand, argued that both the mechanism of action of cangrelor (Kengreal, The Medicines Company) and the available data support its use in most STEMI patients. In acute settings, achieving the desired rapid antiplatelet effect may not be feasible with orally administered therapies such as prasugrel (Effient, Daiichi Sankyo/Eli Lilly) and ticagrelor (Brilinta, AstraZeneca), he said. This may be related to issues such as delayed bioavailability, morphine use, mechanical ventilation, active vomiting, cardiogenic shock, heavy sedation and therapeutic hypothermia.
IV administration of cangrelor, however, offers immediate platelet inhibition within 1 to 2 minutes, White reported. In addition, the offset of action of cangrelor is about 60 minutes, much shorter than the oral agents. Approximately 11% of ACS patients may require surgical revascularization, but after oral P2Y12 inhibitors, 3 to 9 days may be required for return of platelet function.
There is a definite clinical need for cangrelor, White said. It has been shown to significantly reduce early stent thrombosis compared with clopidogrel. He also noted that prasugrel and ticagrelor may increase bleeding events, another point in favor of cangrelor in this population.
More data needed
Sigmund Silber, MD, of Isar Heart Center, Munich, Germany, called for randomized trials comparing cangrelor, prasugrel and ticagrelor in order to demonstrate that cangrelor is the superior pharmacologic option for patients with STEMI. However, such trials have not yet happened, he said.
Pivotal studies involving these agents include TRITON-TIMI 38, PLATO and CHAMPION PHOENIX; the latter led to approval of cangrelor in the United States in June 2015. The studies are not comparable, according to Silber. In TRITON-TIMI 38 and PLATO, 100% of patients had ACS compared with 44% of patients in CHAMPION PHOENIX. Substantial proportions of patients in TRITON-TIMI 38 and PLATO were taking glycoprotein IIb/IIIa inhibitors compared with no patients in CHAMPION PHOENIX. The primary efficacy endpoints also differed among the trials.
“An evidence-based recommendation is not possible,” Silber stressed. Prasugrel represents the simplest option in STEMI patients, he said. The drug has fewer contraindications and warnings than ticagrelor. For example, prasugrel is contraindicated in patients only with severe liver dysfunction, while ticagrelor is contraindicated in those with moderate or severe dysfunction.
Furthermore, European Society of Cardiology guidelines give a class I recommendation to administer a P2Y12 inhibitor at first medical contact, but administering IV cangrelor in an ambulance is not feasible, Silber pointed out. He concluded that while it may be difficult to prove without more data that prasugrel is preferred, it is the best choice of the three therapies.
Crushed ticagrelor another option
Guido Parodi, MD, PhD, of Careggi University Hospital, Florence, Italy, argued that ticagrelor should be considered the preferred treatment option in this population, due to its ability to reduce hard ischemic events in ACS patients without increasing the risk of life-threatening or fatal bleeding. The crushed form of ticagrelor, approved by the FDA in March 2015, could alleviate issues with speed of onset, he suggested, noting, however, that further data are needed to compare the crushed form with other administrations and combinations of therapies.
Given the current data, Parodi said his “provocative” conclusion is: “In STEMI, you can give ticagrelor where, when, how and to whom you want, and you will be right.”
- Parodi reports receiving consultant fees/honoraria from AstraZeneca, Bayer, Eli Lilly and The Medicines Company.
- Silber reports no relevant conflicts of interest.
- White reports receiving grant/research support from several pharmaceutical companies and consultant fees/honoraria from AstraZeneca.