For NSTE-ACS patients undergoing PCI, treatment with ticagrelor soon after admission reduces the risk of periprocedural myonecrosis compared with prasugrel given during the procedure, according to a small study published online May 8, 2015, ahead of print in the American Journal of Cardiology.

“Since periprocedural myonecrosis [has] been associated with short- and long-term clinical outcome[s], the present pilot study supports pretreatment with ticagrelor in intermediate- and high- risk NSTE-ACS,” Laurent Bonello, MD, PhD, of Hôpital Universitaire Nord de Marseille (Marseille, France), and colleagues say.

For the single-center study, investigators randomized patients (mean age 61 years; 74.6% men) with intermediate- or high-risk NSTE-ACS to a 180-mg loading dose of ticagrelor (Brilinta; AstraZeneca) as soon as possible after diagnosis (mean 13.4 hours before PCI; n = 106) or a 60-mg loading dose of prasugrel (Effient; Eli Lilly/Daiichi Sankyo) immediately after the decision to perform PCI (n = 107). The groups received prasugrel maintenance doses of 90 mg twice daily or 10 mg daily, respectively.

All patients, who were treated between January and September 2014, also received a periprocedural intravenous loading dose of 150 mg of aspirin and either a bolus dose of heparin (100 IU/kg) during the procedure followed by an activated clotting time–adjusted additional bolus or standard bivalirudin infusion. DES were implanted via the radial route in all but 2 cases in each group.

Angiographic and interventional characteristics were similar between the study groups, including the mean number of treated vessels. Emergent PCI due to recurrent ischemia between admission and scheduled PCI was more common with prasugrel than ticagrelor (5.6% vs 0%; P < .001). No periprocedural complications were reported in either group.

Advantage for Up Front Ticagrelor

Rates of periprocedural myonecrosis (primary endpoint) and myocardial insult were lower with ticagrelor compared with prasugrel (table 1).

At 24 hours, absolute troponin levels were similar between the ticagrelor and prasugrel groups (2.5 µg/L vs 2.6 µg/L; P = .9).

At 1 month, rates of MACE (cardiovascular death, MI, urgent revascularization, or stroke), its individual components, and Bleeding Academic Research Consortium (BARC) > 2 bleeding were similar between the groups (table 2).

“Platelet-rich thrombus plays a key role in the pathophysiology of ACS,” the authors observe. “[Platelet reactivity] inhibition is therefore critical to prevent complications and ischemic recurrences,” and the present findings support the use of ticagrelor pretreatment, they say.

Is It the Timing or the Drug?

The advantage of the early-ticagrelor strategy may stem from the timing of the loading dose, which enables optimal platelet inhibition and thus earlier and better protection against myonecrosis, Dr. Bonello and colleagues suggest. Or it may derive from the drug’s pleiotropic properties, which could provide added defense against the complex pathophysiology of myonecrosis. Although the trial’s protocol does not permit distinguishing between those explanations, in light of the literature, they add, the most likely reason for ticagrelor’s benefit is the level of inhibition achieved at the time of PCI.

The value of pretreatment was questioned by the failure of prasugrel given prior to PCI to reduce ischemic events in the ACCOAST trial, the authors acknowledge. However, they point to several important differences between the 2 studies, including the fact that up to one-third of ACCOAST patients were managed medically, a subgroup in which prasugrel would not be expected to help. Also, pretreatment in ACCOAST was given a mean 4 hours before PCI—and the pretreatment drug tested was prasugrel—compared with a mean 13.4 hours in the current study.

Possible Need for Surgery a Drawback of Pretreatment

The results of this small, randomized study are “believable, but not to the point where they would influence clinical practice,” Deepak L. Bhatt, MD, MPH, of Brigham and Women’s Hospital (Boston, MA), told TCTMD in a telephone interview.

“Doctors who like to use upstream therapy because it fits into their practice are already doing that with clopidogrel or ticagrelor,” he said. “And for those who prefer to wait until the coronary anatomy is known—as at least half of US physicians do with ACS patients—prasugrel has already been an option.”

In addition, the study is “not entirely a fair comparison for prasugrel because ticagrelor is given sooner,” Dr. Bhatt noted, and the advantage here probably comes from the early timing.”

“This is interesting information, but it doesn’t really tell us which is the better [antiplatelet] strategy,” he contended. “The concern is whether these NSTE-ACS patients may need to go to bypass surgery. If you give upstream ticagrelor, some surgeons will refuse to operate, and the guidelines and the package insert [support] that approach. So it creates a practical dilemma.”

If cangrelor (The Medicines Company)—already given the nod by an FDA advisory committee—is approved, its efficacy together with quick onset and quick offset will make it a good option for physicians who prefer not to pretreat, especially if it is priced reasonably, Dr. Bhatt commented. After the procedure, operators would be free to give whatever antiplatelet drug they wanted, he added.

Bonello L, Laine M, Cluzel M, et al. Comparison of ticagrelor versus prasugrel to prevent peri-procedural myonecrosis in acute coronary syndromes. Am J Cardiol. 2015;Epub ahead of print.

Related Stories:

• PLATO Substudy: Ticagrelor Reduces Mortality in NSTE-ACS Patients Regardless of Revascularization
• Ticagrelor More Rapidly Suppresses Platelet Activity Than Clopidogrel for Low-Risk ACS Patients During Ad Hoc PCI
• Ticagrelor Provides More Potent Platelet Inhibition Than Prasugrel