Genotype- and phenotype-directed antiplatelet therapy selection in patients with acute coronary syndromes

Abstract

Although dual antiplatelet therapy (DAPT) has been a standard treatment in patients with acute coronary syndrome (ACS) for over a decade, only recently have therapeutic options beyond aspirin and clopidogrel become available. Additional treatment options are particularly useful because of the documented history of variability in antiplatelet response. This article reviews the current treatment options for DAPT in ACS, and reviews both genotype- and phenotype-guided methods for determining optimal antiplatelet therapy for patients with ACS. Additionally, recommendations from current guidelines as well as expert commentary are provided for the use of available testing methods to determine optimal DAPT for ACS patients.

Keywords::

• acute coronary syndrome
• antiplatelet
• aspirin
• clopidogrel
• P2Y12 Inhibitors
• personalized medicine
• pharmacogenetic
• prasugrel
• precision medicine
• ticagrelor

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Available options for dual antiplatelet therapy (DAPT) include aspirin and either clopidogrel, prasugrel, or ticagrelor

• A major contributor to high on treatment platelet reactivity (HTPR) is reduced function of the CYP2C19 enzyme in patients.

• CYP2C19 enzyme metabolizer status can be predicted by CYP2C19 genotype; NIH-sponsored guidelines are available to guide use of this genotype in therapeutic decision making.

• Platelet reactivity can also be used to determine antiplatelet response and guide therapeutic decision making; point of care platelet reactivity tests improve the time to receive results.

• The benefit of increasing clopidogrel dose in patients resistant to clopidogrel is controversial and not recommended in patients who are CYP2C19 poor metabolizers.

• Switching from clopidogrel to prasugrel or ticagrelor for patients with HTPR on clopidogrel decreases platelet reactivity with an unclear impact on clinical outcomes has not established.

• Current state of the art suggests that post ACS patients at increased risk for recurrent cardiovascular events and at low risk for bleeding should be treated with a next generation P2Y12 inhibitor.