Study reveals impact of genetic make-up on response to oral antiplatelet treatment ticagrelor

A new genetic substudy of PLATO (A Study of PLATelet Inhibition and Patient Outcomes) showed that the effects on a combined primary endpoint of cardiovascular death, myocardial infarction, or stroke seen in Acute Coronary Syndromes (ACS) patients who received the investigational oral antiplatelet treatment, ticagrelor (BRILINTA™), were maintained, whether or not they had the genetic variability that has been previously shown to affect a patient's response to clopidogrel. The substudy is the first to look at both efficacy and bleeding endpoints of ACS patients treated with ticagrelor who carry variations in the CYP2C19 and ABCB1 genes. The data were presented today at the European Society of Cardiology (ESC) congress in Stockholm, Sweden and simultaneously published in The Lancet.    

CYP2C19

Regardless of the CYP2C19 genotype, the primary outcome occurred less often with ticagrelor versus clopidogrel (interaction>

ABCB1

The genetic substudy also investigated ticagrelor and clopidogrel treatment outcomes in the three genetic groupings of the ABCB1 gene group; these were defined as high, intermediate and low expressions of ABCB1, respectively.  The primary efficacy event rates for ticagrelor were: 9.5% per year for low, 8.5% per year for intermediate, and 8.8% per year for high expression groups. Primary efficacy event rates for clopidogrel were: 10.5% per year for low, 9.8% per year for intermediate, and 11.9% per year for high expression groups. There was no relationship between the ABCB1 genotype and bleeding.

"This substudy is the largest database of ACS patients to date to examine the impact of genetic make-up on response to oral antiplatelet treatment.  As this substudy showed, the effects seen with ticagrelor were independent of genetic variability in CYP2C19 or ABCB1," said Professor Lars Wallentin, primary investigator of the PLATO genetic substudy and Professor of Cardiology and Research Director at the Uppsala University, Sweden.

The substudy was designed to explore the interaction of CYP2C19 and ABCB1 genes on ticagrelor and clopidogrel efficacy and safety. 10,285 ACS patients were genotyped for CYP2C19 and ABCB1 status. On a background of aspirin, patients in the ticagrelor group were given a 180 mg loading dose and a 90 mg twice-daily maintenance dose, while patients in the clopidogrel group were given a 300 mg to 600 mg loading dose and 75 mg once-daily maintenance dose, for 6 to 12 months.