P2Y12 monotherapy wins against aspirin for secondary prevention of CAD

Compared with aspirin alone, treatment with a P2Y₁₂ inhibitor (clopidogrel or ticagrelor) is associated with lower risks of cardiovascular (CV) death, myocardial infarction (MI), or stroke in patients with established coronary artery disease (CAD), according to the PANTHER* trial presented at ESC 2022.

Using data from seven randomized controlled clinical trials (ASCET, CADET, CAPRIE, DACAB, GLASSY, HOST-EXAM, and TiCAB) from 429 sites across Asia, Europe, and North America, the researchers analysed data of 24,352 patients (mean age 64.3 years, 21.7 percent female) with established CAD. These participants had been randomized to receive either aspirin monotherapy (n=12,147) or a P2Y₁₂ inhibitor (n=12,178). In the P2Y₁₂ inhibitor group, 62 percent received clopidogrel and 38 percent received ticagrelor. [ESC 2022, Hot Line Session 9]

Over the study period, with a median treatment duration of 557 days, P2Y₁₂ inhibitor recipients had a lower risk of the primary efficacy endpoint, comprising a composite of CV death, MI, or stroke, compared with aspirin recipients (5.5 percent vs 6.3 percent; hazard ratio [HR], 0.88; p=0.014), with a number needed to treat for benefit of 123 patients to prevent an adverse outcome.

There was no difference in the incidence of major bleeding between the P2Y₁₂ inhibitor and aspirin arms (1.2 percent vs 1.4 percent; HR, 0.87; p=0.23).

The rates of net adverse clinical events, defined as the composite of the primary efficacy endpoint and major bleeding, were lower in the P2Y₁₂ inhibitor arm than the aspirin arm (6.4 percent vs 7.2 percent; HR, 0.89; p=0.02).

When assessing individual components of the composite outcome, patients treated with a P2Y₁₂ inhibitor demonstrated a lower risk of MI than those treated with aspirin (HR, 0.77; p<0.001). There were no significant differences in the risks of CV death (HR, 1.02; p=0.82) or overall stroke (HR, 0.85; p=0.088) between the two treatment arms.

Notably, when stroke subtypes were assessed individually, the risk of haemorrhagic stroke was reduced among those on a P2Y₁₂ inhibitor compared with aspirin (HR, 0.32; p=0.009), but not the risk of ischaemic stroke (HR, 0.93; p=0.45).

The reduction in haemorrhagic stroke was impressive and quite unexpected, said Professor Marco Valgimigli from the Cardiocentro Ticino Institute in Lugano, Switzerland.

The risk of definite stent thrombosis (ST) was reduced among those on a P2Y₁₂ inhibitor compared with aspirin (HR, 0.42; p=0.041), as was definite/probable ST (HR, 0.46; p=0.028) and gastrointestinal bleeding (HR, 0.75; p=0.027).

“Based on all available randomized evidence, long-term P2Y₁₂ monotherapy may be warranted instead of long-term aspirin monotherapy for secondary prevention in patients with CAD,” said Valgimigli, during an ESC press conference. “[However,] I don’t think it’s the end of aspirin. I think it’s more of the rise of an alternative [treatment] to aspirin.”

“[Current] guidelines recommend aspirin as a first-line treatment for CAD, [but] if aspirin is contraindicated, then the second option is to use a P2Y₁₂ inhibitor,” he added. “Now we have at least two equally effective alternatives.”

*PANTHER: P2Y12 inhibitor versus aspirin monotherapy in patients with coronary artery disease