by Payam Dehghani, MD, FRCP(C), FACC, FSCAI
SAN DIEGO — It was previously established in the PLATO trial that ticagrelor is superior to clopidogrel in patients with ACS who were pre-treated with a loading dose. But one question is whether we can extrapolate, as we often do in clinical practice, this finding to troponin-negative patients with an unstable pattern of chest pain.
More than half of all elective PCI procedures in North America are done on an ad-hoc basis immediately after angiography. Think of the last time you had to stop after the diagnostic angiogram so that the patient, covered in sterile prep, can get the loading dose. Mine was just 2 days ago! As common as this scenario is, there is little evidence that ticagrelor (Brilinta, AstraZeneca) is as good as clopidogrel for ad-hoc PCI in low-risk, troponin-negative patients with ACS.
At the Society for Cardiovascular Angiography and Interventions Scientific Sessions, we heard the presentation of pharmacodynamics data showing that in troponin-negative patients with unstable angina platelet reactivity as measured by VerifyNow decreases to a greater extent at 2 hours after a 180-mg loading dose of ticagrelor compared with a 600-mg loading dose of clopidogrel. Roxana Mehran, MD, and fellow investigators randomly assigned 100 patients at 15 U.S. centers to ticagrelor or clopidogrel in the ad-hoc PCI scenario. The percentage of high on-treatment P2Y12 reactivity units was significantly less common in the ticagrelor group at 2 hours compared with the clopidogrel group (13% vs. 78%). What we need to be reminded of, however, is that although this trend was the correct way, ticagrelor did not kick in until the first 30 minutes of PCI, a period which arguably is the most important time for reducing periprocedural MI. Am I asking too much from an orally administered drug? Likely, yes. We already have cangrelor (The Medicines Company), an IV P2Y12 receptor blocker, that does that. Measured in another way, however, by the end of the PCI procedure (shortly after 30 minutes), there was already statistical significant in improved platelet inhibition with ticagrelor compared with clopidogrel.
Back to the trial at hand. Although we now have pharmacodynamic confirmation that ticagrelor is superior to clopidogrel in troponin-negative, low-risk ACS, ad-hoc PCI patients, can we prove there is clinical superiority in this patient population? The trial presented at SCAI 2015 was not powered to answer that question, but sets of the biologic rationale for clinical efficacy in this setting.
What do these pharmacodynamics data add to your strategy in this patient population? Let us know by commenting on this Eye on Intervention blog.
Payam Dehghani, MD, FRCP(C), FACC, FSCAI, is a SCAI 2015-2017 Emerging Leader Mentorship fellow; an interventional cardiologist within the Regina Qu’Appelle Health Region; director of the Adults with Structural Heart Disease Clinic; clinical co-director of the Prairie Vascular Research Network; and assistant professor at the University of Saskatchewan, Canada.
Disclosure: Dehghani reports receiving research grants from AstraZeneca.