PHARMCLO: Outcomes Improved With Genotyping to Select Antiplatelet Therapy
Genotyping to inform selection of antiplatelet therapy in patients with acute coronary syndrome (ACS) improved outcomes compared with the standard of care, according to results presented by Diego Ardissino, MD, FACC, on Sunday, March 11, in a Late-Breaking Clinical Trial session at ACC.18 in Orlando, FL. The results were simultaneously published in the Journal of the American College of Cardiology.
Patients with ACS (n=888) were randomly assigned to P2Y12 receptor antagonist selection based on genotyping and clinical characteristics (n=448) or clinical characteristics alone (n=440), the current standard of care. Patients in the genotyping group were tested for ABCB1 3435, CYP2C19*2 and CYP2C19*17 using the portable ST Q3 system. Antiplatelet selection was ultimately decided by the prescriber. The primary endpoint was the composite of cardiovascular death and the first occurrence of nonfatal myocardial infarction (MI), nonfatal stroke and BARC 3 to 5 major bleeding within 12 months. The secondary endpoint was the composite of the primary endpoint plus occurrence of stent thrombosis.
Enrollment was prematurely stopped by the Ethics Committee after 24.6 percent of the prespecified sample size was enrolled because of the lack of in vitro diagnosis certification for the ST Q3 instrument. All patients were followed up as planned. The differences in antiplatelet prescribing for the genotyping versus standard care group were statistically significant: clopidogrel, 43.3 vs. 50.7 percent; prasugrel, 7.6 vs. 8.4 percent; and ticagrelor, 42.6 vs. 32.7 percent.
The primary endpoint occurred in significantly fewer genotyping versus standard care patients (15.9 vs. 25.9 percent). Stent thrombosis occurred in eight patients, not enough for analysis. Ischemic endpoints occurred in significantly fewer genotyping versus standard care patients (13.0 vs. 21.4 percent). Bleeding endpoints occurred more often in the genotyping versus standard care groups (4.2 vs. 6.8 percent; not significant).
"Selecting treatment on the basis of genetic data in addition to considerations concerning the patients' clinical characteristics may lead to a more personalized, and therefore more efficient, antiplatelet therapy, thus reducing both ischemic and bleeding risk," said Ardissino. "PHARMCLO is the first step of a new approach that will see a shift in emphasis away from trying to discover ever more potent antithrombotic drugs and toward ensuring that the right therapy is given to each individual patient."
"The study, while provocative, was underpowered to detect the endpoint we most fear: stent thrombosis. We need larger trials to know if this strategy works for this critical endpoint," said Kim A. Eagle, MD, MACC, editor-in-chief of ACC.org.
Keywords: ACC18, ACC Annual Scientific Session, Angina, Stable, Acute Coronary Syndrome, Purinergic P2Y Receptor Antagonists, Pharmacogenetics, Genotype, Standard of Care, Ticlopidine, Adenosine, Myocardial Infarction, Hemorrhage, Stroke, Algorithms
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