TRIAGE: Risk algorithm identifies patients who may benefit from intensive antiplatelet therapy

Issue: June 2015

SAN DIEGO — A risk-assessment algorithm that incorporates clinical risk factors and platelet function testing may help to identify patients who might benefit from intensive antiplatelet therapy after PCI, according to results from the TRIAGE study.

The prospective, observational study was conducted at three sites between March 2012 and December 2014. Researchers evaluated outcomes of patients treated with prasugrel (Effient, Daiichi Sankyo/Eli Lilly) compared with clopidogrel at the time of PCI following determination of platelet reactivity in conjunction with clinical risks.

The algorithm combined results from platelet function testing with clinical risk factors, including PCI indication, high angiographic risk PCI and elevated ischemic and bleeding risk scores, to select choice and intensity of thienopyridine therapy In order to be eligible for the study, all patients should have been on uninterrupted clopidogrel therapy for 2 weeks or longer before undergoing elective or urgent PCI. Platelet function was tested immediately prior to PCI using the VerifyNow assay.

Suitable patients with high on-treatment platelet reactivity (P2Y12 reactivity units [PRU] ≥ 230) received prasugrel with a 30 mg or 60 mg loading dose and patients with low on-treatment platelet reactivity continued to receive clopidogrel, as indicated by the algorithm Due to slow enrollment, study recruitment was terminated at 318 patients (mean age, 65.9 years; 19% women). Of those, 72% received clopidogrel after PCI and 28% received prasugrel.

The primary efficacy endpoint was a composite of death, nonfatal MI and definite/probable stent thrombosis at 1 year. The primary safety endpoint was major bleeding as indicated by BARC of 2, 3 or 5 at 1 year.

Jaya Chandrasekhar

The rate of major adverse cardiac events at 1 year was 4.4% among patients with high on-treatment platelet reactivity who received prasugrel compared with 3.5% for patients withlow reactivity who received clopidogrel (P = .7), according to results presented at the Society for Cardiovascular Angiography and Interventions Scientific Sessions by Jaya Chandrasekhar, MBBS, from the Icahn School of Medicine at Mount Sinai in New York.

When examined alone, there were no differences between the prasugrel and clopidogrel groups in the incidence of death (4.4% vs. 1.8%), stent thrombosis (0% vs. 0.4%), spontaneous nonfatal MI (1.1% vs. 2.2%), unplanned target vessel revascularization (6.7% vs. 7%) or a composite of death, stent thrombosis and periprocedural and nonfatal MI (5.6% vs. 9.2%).

Chandrasekhar said there was “no untoward increase” in bleeding with prasugrel compared with clopidogrel. At 1 year, the rate of BARC 2, 3 or 5 bleeding was 5.6% among patients who received prasugrel compared with 7.9% among patients who received clopidogrel (P = .47).

The researchers also studied the use of different PRU cut-offs. With a cut-off of 230, the rate of MACE at 1 year was 5.7% for patients with PRU ≥ 230 vs. 2.8% for < 230 (P = .21). With a cut-off of 208, the rate of MACE at 1 year was 6% for those with PRU ≥ 208 vs. 2.2% for < 208 (P = .08).

“Use of platelet function testing may identify more patients at a high ischemic risk than clinical assessment alone,” Chandrasekhar concluded. “The best PRU cut-off for high on-treatment platelet reactivity in a real-world unselected population for risk prognostication is undetermined. The effect of a tailored, integrated assessment for thienopyridine prescription needs randomized examination in future trials.”

Reference:

Chandrasekhar J, et al. Late-Breaking Clinical Trials. Presented at: Society for Cardiovascular Angiography and Interventions Scientific Sessions; May 6-9, 2015; San Diego.

Disclosure: The researchers report no relevant financial disclosures.