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PLATO: Ticagrelor associated with reductions in mortality in CABG-treated patients vs. clopidogrel

Held C. J Am Coll Cardiol. 2011;57:672-684.
Schneider D. J Am Coll Cardiol. 2011;57:685-687.

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Patients who underwent CABG within 7 days of last study drug intake had improved CV and total mortality outcomes with ticagrelor when compared with clopidogrel, according to results of a substudy of the PLATO trial.

The analysis of the Platelet Inhibition and Patient Outcomes (PLATO) trial included only patients who underwent CABG after randomization (n=1,899). Of these patients, 1,261 had a last intake of ticagrelor (Brilinta, AstraZeneca; n=632) or clopidogrel (Plavix, Sanofi-Aventis; n=629) within 7 days before CABG.

At 12 months, the relative reduction for the primary composite endpoint of CV death, MI or stroke favored ticagrelor with a rate of 10.6% vs. 13.1% in the clopidogrel arm (HR=0.84; 95% CI, 0.60-1.16). Statistically significant reductions were reported in the ticagrelor arm in total mortality (4.7% vs. 9.7%; HR=0.49; 95% CI, 0.32-0.77) and CV mortality (4.1% vs. 7.9%; HR=0.52; 95% CI, 0.32-0.85), whereas a non-statistically significant reduction was also found in non-CV death (0.7% vs. 2%; HR=0.35; 95% CI, 0.11–1.11).

In an editorial accompanying the PLATO substudy, David J. Schneider, MD, with the Cardiovascular Research Institute, University of Vermont in Burlington, wrote that the findings of this PLATO sub-study demonstrate a directionally consistent but greater reduction in CV mortality compared with that in the parent trial.

“(Future research) should focus on mechanisms responsible for the greater reduction in CV mortality to enhance our understanding and improve care of patients with CVD,” Schneider said. “Two characteristics of ticagrelor that merit additional study are reversibility of its binding to P2Y12 and its inhibition of adenosine uptake into erythrocytes.”

Disclosure: Dr. Schneider reports having received consulting fees and grants from Johnson & Johnson, Bayer Pharmaceuticals, The Medicines Company, Sanofi-Aventis and Bristol-Myers Squibb.

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