Evolving evidence for P2Y12 inhibition in chronic coronary syndromes: PANTHER

A patient-level meta-analysis suggests similar safety and lower ischaemic risk with P2Y12 inhibition versus aspirin alone. These results challenge the central role of aspirin for prevention and shift the momentum toward P2Y12 inhibitor monotherapy for secondary prevention in the long-term antithrombotic management of patients with CAD.

Prof. Marco Valgimigli (Cardiocentro Ticino Foundation, Switzerland) presented the PANTHER meta-analyses [1] including patient-level data from 7 trials evaluating the effect of monotherapy P2Y12 inhibitors (clopidogrel, prasugrel, or ticagrelor) versus aspirin on adjudicated ischaemic and bleeding outcomes in patients with established coronary artery disease: ASCET, CADET, CAPRIE, DACAB, GLASSY, HOST-EXAM, and TiCAB (analysed cohort n=24,325; mean age 64 years; 22% women; median treatment duration 557 days) [2–8].

The risk of the primary efficacy endpoint of cardiovascular death, myocardial infarction (MI), and stroke was lower by 12% with P2Y12 inhibitor monotherapy compared with aspirin monotherapy (5.5% vs 6.3%; HR 0.88; 95% CI 0.79–0.97; P=0.014). This result was attributable in large part to the association of P2Y12 inhibitor monotherapy with a lower risk of MI compared with aspirin (2.3% vs 3.0%; HR 0.77; 95% CI 0.66–0.90; P<0.001).

Safety was similar between aspirin and P2Y12 inhibition, with the risk of major bleeding being the same (1.4% vs 1.2%; HR 0.87; 95% CI 0.70–1.09; P=0.23). Some differences in other secondary endpoints were observed. For example, the risk of net adverse clinical events, defined as the composite of the primary efficacy endpoint and major bleeding, was reduced in participants receiving P2Y12 inhibitor monotherapy compared with aspirin monotherapy (6.4% vs 7.2%; HR 0.89; 95% CI 0.81–0.98; P=0.020).

Prof. Valgimigli summarised: “The relative risk of the primary composite endpoint was reduced by 12% in patients receiving a P2Y12 inhibitor, primarily driven by a 23% relative reduction of MI and, secondarily, by a numerical but not significant lower rate of stroke. The overall risk of major bleeding did not differ, whereas gastrointestinal bleeding and haemorrhagic stroke occurred less frequently in patients receiving a P2Y12 inhibitor than aspirin monotherapy.”

1. Valgimigli M, et al. PANTHER - P2Y12 inhibitor versus aspirin monotherapy in patients with coronary artery disease. Hot Line Session 9, ESC Congress 2022, Barcelona, Spain, 26–29 August.
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8. Koo BK, et al. Lancet. 2021;397:2487–2496.

 

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Posted on 27 October 202226 October 2022