Debate focuses on appropriateness of cangrelor, pretreatment with oral antiplatelets in patients undergoing PCI

BOSTON — At the Cardiometabolic Health Conference, one expert argued IV cangrelor should be used during PCI and has rendered the practice of preloading with oral antiplatelets unnecessary, while another expert said the practice of preloading with oral antiplatelets is still a good idea in some patients.

Gregg W. Stone, MD, professor of medicine at Columbia University, director of cardiovascular research and education at the Center for Interventional Vascular Therapy at NewYork-Presbyterian Hospital/Columbia University Medical Center, and co-director of medical research and education at the Cardiovascular Research Foundation, said cangrelor (Kengreal, The Medicines Company) has been shown to be superior to clopidogrel and is especially helpful in patients unable to take oral medications.

Gregg W. Stone

The question, he said, is whether an oral P2Y12 inhibitor such as clopidogrel, ticagrelor (Brilinta, AstraZeneca) or prasugrel (Effient, Daiichi Sankyo/Eli Lilly) should be given before enough is known about the coronary anatomy in a patient with ACS to determine whether PCI, CABG or another option is best.

“I used to believe in this. We used to give out clopidogrel like water,” Stone said.

However, the intention-to-treat analyses of the CREDO, PRAGUE 8 and ACCOAST studies found no difference in event rate between those who were preloaded with a P2Y12 inhibitor and those who were not, according to Stone.

“You would think preloading would protect you during the PCI procedure, but it actually didn’t,” he said. “What it did was significantly increase the risk of major and minor bleeding.”

Now, he said, operators can instead use cangrelor, an IV P2Y12 inhibitor, during PCI and no longer worry about preloading.

“The amazing thing about this drug is it’s incredibly potent, essentially abolishing 100% of [adenosine diphosphate-induced] platelet activation. In addition, you give it and in a couple of minutes you’ve got platelet inhibition, and it’s very rapidly reversed, so if bleeding starts and you shut off the infusion, within 30 to 60 minutes, platelet function is restored to normal. That’s a huge benefit because with all the oral agents, it’s anywhere from 3 to 7 days before normal platelet function returns.”

Other advantages of cangrelor is that it can be used in patients who cannot take oral medications, and it doesn’t need to be given until the patient is in the cath lab and the decision has been made to perform PCI, so it won’t be administered to those who don’t need PCI, according to Stone.

In the CHAMPION PHOENIX trial, cangrelor was associated with an approximately 20% relative reduction in event rate vs. clopidogrel (P = .006). Much of the difference occurred within the first 2 hours and was consistent across patients with STEMI, non-ST elevation ACS or stable angina, he said.

“We don’t see thrombus forming inside the stents of our patients by using this agent,” he said.

Bleeding risk, except for hematomas at the groin site, is not increased vs. clopidogrel because of how easily reversible cangrelor is, he said.

In many centers, for stable patients, it takes approximately 20 hours between presentation to the ED and transfer to the cath lab, according to Kenneth W. Mahaffey, MD, vice chair of clinical research in the department of medicine at Stanford School of Medicine and director of Stanford Center for Clinical Research.

“In an institution like mine, that does a next-day cath strategy unless [the patient is] unstable,” cangrelor is not the solution for every patient, he said. Pretreatment may still be appropriate in certain patients before they get to the cath lab, according to Mahaffey.

The CHAMPION PHOENIX trial does not provide answers to that question because there was no pretreatment, he said.

U.S. and European guidelines do not take a stand on pretreatment because of lack of clear evidence on the optimal time to begin preloading, he said.

“Clearly, patients who go to the cath lab quickly” should receive cangrelor, he said. “But if you have a delay, or your institution requires transfer to a facility that has catheterization abilities, then I still think that in patients at high risk for ischemic complications and low risk for bleeding should be pretreated with P2Y12 inhibition.” – by Erik Swain

Reference:

Mahaffey KW, Stone GW. The Latest in Antithombotic Therapy: The Experts Take Sides. Presented at: Cardiometabolic Health Congress; Oct. 5-8, 2016; Boston.

Disclosure: Mahaffey reports receiving research funding from Amgen, AstraZeneca, Daiichi Sankyo, Johnson and Johnson, Medtronic, Merck, Sanofi and Tenax; receiving consultant fees from AstraZeneca, BAROnova, Bayer, Boehringer Ingelheim, Bio2 Medical, Bristol-Myers Squibb, Cubist, Eli Lilly, Elsevier, Epson, Forest, GlaxoSmithKline, Johnson & Johnson, Medtronic, Merck, MyoKardia, Omthera, Portola, Purdue, Springer, The Medicines Company, Theravance, Vindico and WebMD; and holding equity in BioPrint Fitness. Stone reports no relevant financial disclosures.