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November 11, 2021 - After acute coronary syndrome, dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is recommended for a period of time to help prevent stent thrombosis and/or myocardial infarction (see AHA DAPT recommendations). The optimal length of DAPT and which P2Y12 inhibitor to use are the subject of much debate.

A study published in The Lancet compared DAPT with ticagrelor to DAPT with clopidogrel in patients who had undergone PCI with drug-eluting stents for acute myocardial infarction. Patients completed one month of DAPT with ticagrelor and were then randomized to continue ticagrelor or switch to clopidogrel. The primary outcome was a composite of cardiovascular death, myocardial infarction, stroke, and BARC bleeding (type 2, 3, or 5) at 12 months post PCI. At the end of the study, clopidogrel was found to be superior to ticagrelor for the composite outcome (4.6% vs 8.2%, p=0.0001) and bleeding events (3% vs 5.6%, p=0.0012). It was also noninferior to ticagrelor for a composite of CV death, MI, or stroke (2.1% vs 3.1%, p=0.15) [SH review].

A unique aspect of this study is that it was only performed in South Korea, a population with a high prevalence of CYP2C19 loss-of-function alleles. Clopidogrel is a prodrug that must be metabolized by CYP2C19 to become active. Some studies have suggested that clopidogrel may not be as effective in patients with poor-metabolizer genotypes; this led the FDA to place a boxed warning on clopidogrel that states physicians should "consider use of another platelet P2Y12 inhibitor in patients identified as CYP2C19 poor metabolizers." The results of this study do not support their guidance.

This is the second study published in the last two years that has found clopidogrel to be superior to ticagrelor in DAPT. The other study found that clopidogrel was safer than ticagrelor in patients who were 70 years and older. A third study published in 2019 that compared ticagrelor to prasugrel found that prasugrel was superior.


Antiplatelet therapy in CAD

Clopidogrel and CYP2C19 poor metabolizers

P2Y12 inhibitors