Debate continues over pretreatment with platelet receptor inhibitors

SAN FRANCISCO — Although data suggest there is no benefit to pretreating most patients with platelet receptor inhibitors before PCI, there may be a benefit in patients with STEMI, experts said at TCT 2013.

The literature suggests various clinical benefits for patients with STEMI pretreated with prasugrel (Effient, Eli Lilly), ticagrelor (Brilinta, AstraZeneca) and clopidogrel (Plavix, Sanofi-Aventis), Michel Le May, MD, FRCC, FACC, of the University of Ottawa Heart Instititute, Ottawa, Canada, said.

Deepak L. Bhatt

However, the ACCOAST trial and other studies have shown that the risks of pretreatment outweigh the benefits for non-STEMI patients, according to Deepak L. Bhatt, MD, MPH, FACC, FAHA, FSCAI, FESC, of the VA Boston Healthcare System.

“There is no role for prasugrel pretreatment in non-STEMI patients,” said Bhatt, who is Chief Medical Editor of Cardiology Today's Intervention. “Pretreatment is on shaky ground.”

Benefit in STEMI patients

A meta-analysis of randomized trials showed that patients with STEMI pretreated with clopidogrel before PCI had lower all-cause mortality rates than patients with STEMI who were not pretreated (OR=0.5; 95% CI 0.26-0.96; P=.02). Subsequent trials suggest that preloading STEMI patients with prasugrel or ticagrelor is more effective than preloading them with clopidogrel, Le May said.

In the TRITON-TIMI 38 STEMI study, patients preloaded with prasugrel had lower rates of death/MI recurrence/stroke (primary PCI, P=.0017; secondary PCI, P=.0221), death/MI recurrence/urgent target vessel revascularization (primary PCI, P=.0205; secondary PCI, P=.025) and stent thrombosis (primary PCI, P=.0084; secondary PCI, P=.0232) vs. those preloaded with clopidogrel; there was no difference in major bleeding (primary PCI, P=.3359; secondary PCI, P=.6451).

In the PLATO STEMI trial, patients preloaded with ticagrelor had better outcomes but a higher risk for stroke (HR=1.63; 95% CI, 1.07-2.48; P=.02) compared with those preloaded with clopidogrel.

However, Le May said, only 71% of patients with STEMI see a potential net benefit with prasugrel because of risk for bleeding, so his institution uses ticagrelor.

“We’ve chosen ticagrelor because of its properties in reducing mortality overall in the PLATO trial, and because there are not all these exclusions that you see with prasugrel in terms of risks of [transient ischemic attack] and stroke,” he said.

Cangrelor shows promise

Debate about preloading aside, Bhatt said that the novel direct platelet P2Y12 receptor antagonist cangrelor (The Medicines Company) may prove more effective than any anticoagulant available today.

In the CHAMPION PHOENIX trial, PCI patients assigned cangrelor had a 4.7% rate of the primary endpoint of death, MI, ischemia-driven revascularization or stent thrombosis at 48 hours vs. 5.9% for PCI patients assigned clopidogrel (P=.006). The effect was consistent across subgroups and there was no difference in bleeding indicators except by the highly sensitive ACUITY Major score, which favored clopidogrel, Bhatt said.

Those assigned cangrelor also had a lower rate of intra-procedural stent thrombosis — which was associated with 30-day mortality — than those assigned clopidogrel (0.6% vs. 1%; P=.04).

“If it is approved and the cost is not prohibitive, cangrelor could become the treatment of choice,” Bhatt said.

For more information:

Bhatt DL. Adjunctive Pharmacotherapy: The Debate Continues.

Le May M. Adjunctive Pharmacotherapy: The Debate Continues. Both presented at: TCT 2013; Oct. 27-Nov. 1, 2013; San Francisco.

Disclosure: Bhatt and Le May report financial disclosures with several device and pharmaceutical manufacturers.