P2Y12 Inhibitors May Be the Better Option for Secondary Prevention in CAD

BARCELONA -- Patients with documented coronary artery disease (CAD) saw cardiovascular benefits with P2Y12-inhibitor monotherapy when compared with aspirin alone, according to the PANTHER meta-analysis.

The study's primary outcome -- risk of cardiovascular death, myocardial infarction, and stroke -- occurred in 5.5% of those on a P2Y12 inhibitor versus 6.3% of those on aspirin (HR 0.88, 95% CI 0.79-0.97, P=0.014), reported Marco Valgimigli, MD, PhD, of the University Hospital of Bern in Switzerland.

Major bleeding rates were similar between the P2Y12-inhibitor and aspirin groups (1.2% vs 1.4%, respectively, P=0.23), he said at a press conference at the annual European Society of Cardiology (ESC) congress.

These two outcomes combined for a lower risk of net adverse clinical events (NACE) in the P2Y12-inhibitor group (6.4% vs 7.2%; HR 0.89, 95% CI 0.81-0.98, P=0.020), with a number needed to treat of 121 to prevent one NACE with P2Y12 inhibitors.

Valgimigli explained that studies of P2Y12-inhibitor monotherapy -- clopidogrel or ticagrelor -- versus aspirin monotherapy have yielded mixed results.

The findings from the seven-study patient-level meta-analysis "challenge the central role of aspirin and support a paradigm shift toward single P2Y12 inhibition for secondary prevention in the long-term antithrombotic management of patients with coronary artery disease," he stated in an ESC press release.

"This is an important study for patients who had a heart attack, angioplasty, a stroke, or bypass surgery -- a person should be on antiplatelet therapy to prevent a second event," Manesh Patel, MD, of Duke University in Durham, North Carolina, told MedPage Today.

Patel, who was not involved in the study, pointed out that while the CAPRIE study showed clopidogrel to be better than aspirin for preventing secondary events, the findings were not widely adopted, likely due to the cost of clopidogrel at that time. Generic P2Y12 inhibitors are now available and cost roughly the same as aspirin.

"Now, PANTHER shows the same thing, that there is a benefit of P2Y12 inhibitors in preventing these events compared with aspirin," said Patel.

He cautioned that the results do not necessarily apply to people who have not experienced a cardiac event. "When you take a stronger drug, such as the P2Y12 inhibitors, you are running a bleeding risk," he said, advising that aspirin would be a better bet in primary prevention.

The U.S. Preventive Services Task Force recently issued updated guidance on aspirin for primary prevention, recommending (with a C grade) that aspirin may be appropriate in some high-risk adults ages 40 to 59, but not for those 60 and older.

The PANTHER meta-analysis included seven trials -- ASCET, CADET, CAPRIE, DACAB, GLASSY, HOST-EXAM, and TiCAB -- conducted at 492 sites across Europe, Asia, and North America. After exclusions, the final study population included 24,325 patients (mean age 64.3 years, 21.7% women), with 12,178 assigned to P2Y12-inhibitor monotherapy (clopidogrel or ticagrelor) and 12,147 to aspirin alone. Median treatment duration was 557 days.

Comment