PANTHER analysis suggests P2Y12 inhibitors safer, more effective than Aspirin, for secondary prevention

By Leah Kosyakovsky on

Key Points

  • Antiplatelet therapy is a cornerstone of secondary prevention in patients with known CAD, but it is incompletely understood whether aspirin should be the preferred agent as compared to oral P2Y12 inhibitors. The PANTHER collaborative initiative was an individual patient data meta-analysis which sought to assess the effect of ASA vs PSY12 inhibitor monotherapy on long-term cardiovascular outcomes in patients with known CAD.
  • Treatment with oral P2Y12 inhibitor therapy, as compared to ASA, resulted in lower composite CV events (including MI, CV death, and stroke) and similar bleeding risk, although with specifically reduced risk of GI bleeding and hemorrhagic stroke. The reduced composite CV events were largely driven by a significant reduction in MI in the P2712 inhibitor group.

Antiplatelet therapy is a cornerstone in the management of patients with established coronary disease, and European and American guidelines recommend ASA as a first-line option for treatment. However, the relative benefit of aspirin vs P2Y12 inhibitors in secondary prevention for CAD is incompletely understood. In a breaking presentation at the 2022 European Society of Cardiology Conference today, Dr. Marco Valgimigli (University Hospital Bern, Switzerland) and his team presented their individual patient data meta-analysis, “P2Y12 inhibitor or Aspirin moNoTHERapy as secondary prevention in patients with coronary artery disease: in individual patient data meta-analysis,” or the PANTHER collaborative initiative.

The PANTHER initiative was an individual patient data meta-analysis assessing the effect of single-agent aspirin vs oral P2Y12 inhibitor therapy in patients with known coronary disease without an indication for anticoagulation.  A total of 7 trials were included, which included >24,000 from 492 sites worldwide, half of which had been assigned to P2Y12 inhibitor therapy and half to ASA. Among the P2Y12 inhibitor patients, 62% were treated with clopidogrel and the remainder with ticagrelor. The mean age was 64, and 21% of patients were women. The prespecified primary endpoint was a composite of CV death, MI, and stroke; over a follow-up period of two years, patients treated with PSY12 inhibitor therapy had a significantly lower risk of this composite primary endpoint (HR 0.88, CI 0.79-0.97; p =0.014). The primary safety endpoint, a composite of major bleeding, was not significantly different between the two groups. Of the secondary outcomes of interest, P2Y12 inhibitor therapy resulted in lower rates of MI (p<0.001), hemorrhagic stroke (p=0.009), and GI bleeding (p=0.027).

When discussing the implications of the study at the ESC, Dr. Valgimigli stated: “P2Y12 inhibitor monotherapy was associated with a lower risk of our composite endpoint…compared with aspirin monotherapy in patients with known coronary disease, mainly owing to a lower risk of myocardial infarction….the incidence of bleeding was overall similar, but gastrointestinal bleeding and hemorrhagic stroke was lower with P2Y12 inhibitor monotherapy…based on available randomized evidence, long-term P2Y12 inhibitor monotherapy may be warranted instead of aspirin monotherapy for secondary prevention of coronary artery disease.”