• PANTHER Meta-Analysis: P2Y12 Inhibitor Monotherapy Lowers Risk of CV Death, MI or Stroke vs. Aspirin Monotherapy in CAD

    P2Y12 inhibitor monotherapy was associated with lower risks of cardiovascular death, myocardial infarction (MI) or stroke as compared with aspirin monotherapy in patients with coronary artery disease (CAD), according to a new meta-analysis.

    Marco Valgimigli, MD, PhD, of the Cardiocentro Ticino Foundation, Lugano, Switzerland, reported these findings from the PANTHER study Monday at the European Society of Cardiology (ESC) Congress 2022 in Barcelona, Spain.

    The PANTHER study was an individual participant-level meta-analysis of seven trials that randomized patients to monotherapy with a P2Y12 inhibitor or aspirin. The trials included 35,752 individual participants from 492 sites across Asia, Europe and North America.

    The study population consisted of 24,325 patients, 12,178 of whom were assigned to P2Y12 inhibitor monotherapy (7,545 [62%] to clopidogrel, 4,633 [38%] to ticagrelor) and 12,147 assigned to aspirin monotherapy. The median treatment duration was 557 days.

    The primary efficacy outcome was a composite of cardiovascular death, MI or stroke. A primary-outcome event occurred in 5.5% of the P2Y12 inhibitor patients, which was significantly lower than the 6.3% rate in aspirin patients (hazard ratio [HR]: 0.88; 95% confidence interval [CI]: 0.79 to 0.97; p=0.014; number needed to treat [NNT] = 123).

    Valgimigli said this difference was driven by a lower risk of MI in the P2Y12 inhibitor arm (HR: 0.77; 95% CI: 0.66 to 0.90; p<0.001).

    Turning to secondary outcomes, the risk of major bleeding was similar between the arms (P2Y12 inhibitor 1.2% vs. aspirin 1.4%; HR: 0.87; 95% CI: 0.70-1.09; p=0.23). The risk of net adverse clinical events, defined as a composite of the primary outcome and major bleeding, was 6.4% in the P2Y12 inhibitor arm, which was significantly lower than the 7.2% rate in the aspirin arm (HR: 0.89; 95% CI: 0.81-0.98; p=0.020; NNT = 121).

    Valgimigli said these results suggest that long-term P2Y12 inhibitor monotherapy might be warranted instead of long-term aspirin monotherapy in patients with CAD.

    But he demurred when asked during a press conference if this is “beginning of the end of aspirin” for secondary prevention of CAD.

    “I don’t think it’s the end of aspirin,” Valgimigli said. “I think it’s the rise of an available alternative to aspirin.”

    After explaining that there has been a hint that clopidogrel could be considered better than aspirin, he said the two drugs might be considered “at least equally effective alternatives.”

    “To take aspirin completely out of the picture – probably that would require additional studies because aspirin has been there for 125 years,” he said.

    The PANTHER study was supported by institutional funding from Cardiocentro Ticino and Inselspital, Bern, Switzerland.

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