TCT: Platelet reactivity monitoring bests standard prasugrel Rx for bleeds, thrombotic events

MIAMI—Platelet reactivity monitoring is superior to a one-dose-fits-all strategy with prasugrel in reducing the rate of both high and low on-treatment platelet reactivity, which in turn impacts the adverse event rates in those patients, according to a study presented Oct. 22 at the 2012 Transcatheter Cardiovascular Therapeutics (TCT) conference.

“Based on a wealth of trial data, there is a strong relationship between platelet reactivity inhibition and thrombotic events,” said lead investigator Laurent Bonello, MD, a cardiologist at Hopital Universitaire Nord and Universite de la Mediterranee, both in Marseille, France. “Moreover, higher platelet reactivity inhibition is associated with increased bleeding rates.”

Prasugrel (Effient, Eli Lilly/Daiichi Sankyo) has been shown to induce a higher platelet reactivity inhibition following the loading dose, compared with clopidogrel (N Engl J Med 2007;357:2001-2015). “This translates into a lower ischemic risk, but a higher rate of bleedings,” he said. “Also, prasugrel shares similar active metabolites with clopidogrel.”

Also, a multicenter, prospective, observational (real-life) study that enrolled 301 patients found “a good response to prasugrel, [but] there are still some patients demonstrating high on-treatment platelet reactivity [HTPR],” said Bonello. In this trial, those patients with HTPR had more thrombotic events, but patients with very low platelet reactivity (16 percent) had more bleeding (J Am Coll Cardiol 2011;58[5]:467-473).

“Thus, it stood to reason that if a patient has HTPR, he or she is more prone to thrombotic events, and if a patient has low platelet reactivity, he or she is more prone to bleeds,” he said.

In this multicenter, randomized, open-label, prospective study, Bonello et al sought to compare platelet reactivity monitoring with standard prasugrel therapy to reduce the rate of HTPR in patients undergoing PCI for an acute coronary syndrome. The researchers used the VASP (vasodilator-stimulated phosphoprotein) index to assess platelet reactivity.

The primary endpoint was the rate HTPR (defined by VASP index) above 50 percent upon discharge. The secondary endpoints were the percentage of patients with platelet reactivity less than 16 percent, the percentage of patients with platelet reactivity between 16 and 50 percent; ischemic events, including cardiovascular death, MI or stent thrombosis; and bleeding events.

In the study, 89 patients were administered 60 mg loading dose of prasugrel, and 88 patients were administered 600 mg loading dose of clopidogrel. Sixty percent of the patients were non-STEMI; all had PCI and none had emergent CABG.

Prasugrel was found to be superior to clopidogrel (45.5 vs. 25.8 percent), reported Bonello. Also, fewer patients exhibited HTPR with prasugrel: 15.7 vs. 43 percent.

Platelet reactivity monitoring was found to be “very efficient,” he said. In the platelet reactivity monitoring group, clopidogrel adjustments, using up to three additional loading doses, VASP index was significantly decreased: 30.9 vs. 45.5 percent. This reduced the number of patients with HTPR from 44.3 to 2.3 percent.

Thus, platelet reactivity monitoring is superior to prasugrel standard therapy. Upon discharge, the VASP index was similar: 30.9 vs. 25.8 percent. However, the HTPR rate was lower in the platelet reactivity monitoring group, compared with the prasugrel standard therapy group: 2.3 vs. 15.7 percent. The rate of patients with low on-treatment platelet reactivity was lower in the platelet reactivity monitoring group, compared with the standard therapy prasugrel group: 14.6 vs. 53.4 percent.

Finally, the rate of patients within the therapeutic window of platelet reactivity was higher in the platelet reactivity monitoring group compared with the prasugrel group (83 vs. 42 percent).

Therefore, Bonello concluded that “platelet reactivity monitoring may help to better tailor P2Y12 ADP receptor to balance bleedings and ischemic events.”

Bonello stressed that the purpose of the study wasn’t to discourage the use of prasugrel therapy, but instead to promote the use of platelet reactivity testing to tailor therapy and reduce events in the at-risk time post PCI.