Presentations Examine Multiple Facets of Antiplatelet Agents

MIAMI BEACH, FLA.—Data presented at TCT 2012 indicate that platelet reactivity monitoring could establish a therapeutic window for patients with high bleeding or ischemic risk, in which thrombotic events are prevented without increasing bleeding risk.

Laurent Bonello, MD, from the Hôpital Universitaire Nord in Marseille, France, presented data from a trial currently in press in which researchers  randomly assigned 177 ACS patients undergoing PCI to receive either prasugrel 60 mg loading dose (n=89) or clopidogrel 600 mg loading dose with dose adjustment after platelet function testing (VASP analysis; n=88).

Results showed similar VASP index on discharge (31 ±14% vs. 26 ±23%; P=.08). High on-treatment platelet reactivity on discharge was significantly lower in the platelet reactivity monitoring group (2.3% vs. 15.7%; P=.005), as was the rate of low-on-treatment platelet reactivity (14.6% vs. 53.4%; P<.0001). In addition, platelet function monitoring increased the rate of patients within the therapeutic window of platelet reactivity compared with those receiving prasugrel alone (83% vs. 42%).

 “According to the results of this study, the hypothesis of a therapeutic window of platelet reactivity seems confirmed for clopidogrel,” Bonello said. “Data regarding platelet reactivity monitoring in the prasugrel era suggests that the cut-off values to define such a therapeutic window exist – if confirmed, this could be helpful in several subgroups of patients with high bleeding or ischemic risk.

Specific agents for specific cohorts

In another presentation, Dirk Sibbing, MD, of the German Heart Centre and Technical University of Munich in Germany, looked at P2Y12 inhibitors in specific subsets of patients, including those with STEMI from the TRITON-TIMI 38 trial.

In the trial, published in the Lancet in 2009 by Montalescot et al, 3,534 patients presenting with STEMI were randomly assigned to either prasugrel (60 mg loading, 10 mg maintenance [n=1,769]) or clopidogrel (300 mg loading, 75 mg maintenance [n=1,765]). The primary endpoint was CV death, non-fatal MI or non-fatal stroke.

At 30 days, 115 (6.5%) patients assigned to prasugrel met the primary endpoint compared with 166 (9.5%) allocated to clopidogrel (HR=0.68; 95% CI 0.54-0.87; P=.0017). This effect continued to 5 months (10.0% vs. 12.4%; P=.0221).

“Mechanistic data argue for the use of more potent antiplatelet drugs,” Sibbing said during the presentation. “Intensified antiplatelet treatment, regardless of whether it was prasugrel or ticagrelor, was superior to standard clopidogrel in reducing ischemic events. In addition, the benefit with regard to ischemic risk reduction was found without any increased bleeding risk.

Predicting patient CV risk

Michelle O’Donoghue, MD, MPH, of Brigham and Women’s Hospital in Boston, presented analyses on genotyping and platelet function testing, which also included an analysis of the TRITON-TIMI 38 trial, in this case published in the New England Journal of Medicine in 2009 by Mega et al. The analysis compared 162 healthy patients with 1,477 ACS patients. Both groups were treated with clopidogrel.

In healthy patients, carriers of at least one CYP2C19 reduced-function allele had a relative reduction of 32.4% in plasma exposure to the active metabolite of clopidogrel compared with non-carriers (P<.001). Among clopidogrel-treated subjects, carriers had a relative increase of 53% in the composite primary efficacy outcome of the risk of CV death, MI or stroke compared with noncarriers (12.1% vs. 8.0%; HR for carriers=1.53; 95% CI, 1.07-2.19; P=.01).

“If one opts to treat all patients with a third-generation ADP receptor blocker (prasugrel or ticagrelor), then it could be argued that platelet function or genotyping is not necessary,” O’Donoghue said. “However, as clopidogrel now becomes generic and cost becomes an important factor … then knowing a patient’s CYP2C19 carrier status or their on-treatment platelet reactivity might influence this decision to either continue to treat with clopidogrel or switch to another agent.”