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Ticagrelor Pharmacogentetics

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – While clopidogrel’s effectiveness in the treatment of acute coronary syndromes is affected by a patient’s genotype, the efficacy of ticagrelor is not. Therefore, ticagrelor eliminates the need for genetic testing recommended before dual antiplatelet therapy, a multicenter team reports in The Lancet online August 29.

Furthermore, ticagrelor is more efficacious than clopidogrel regardless of genotype, the researchers found.

The findings come from an analysis of data from the PLATO trial comparing ticagrelor to clopidogrel for treatment of ACS. Because single nucleotide polymorphisms in CYP2C19 and ABCB1 genes are known to modulate the effects of clopidogrel, Dr. Lars Wallentin at Uppsala University, Sweden and colleagues genotyped DNA samples from 10,285 participants in the trial.

“For the CYP2C19 genotype, patients were stratified by the presence or absence of any loss-of-function allele,” the researchers explain, “and for the ABCB1 genotype, patients were stratified by predicted gene expression (high, intermediate, or low).”

Among participants who had any loss-of-function CYP2C19 allele, the primary outcome — a composite of cardiovascular death, MI or stroke after treatment for up to 12 months — occurred in 8.6% of patients on ticagrelor versus 11.2% of those on clopidogrel (HR 0.77; p=0.0380).

Among the participants without any loss-of-function allele, corresponding rates were 8.8% vs. 10.0% (HR 0.86, p=0.0608), Dr. Wallentin and colleagues found.

“In relation to the ABCB1 genotype,” they write, “rates of cardiovascular death, myocardial infarction, and stent thrombosis were consistently lower in the ticagrelor group than in the clopidogrel group, irrespective of ABCB1 polymorphism.”

Major bleeding was more frequent in patients on clopidogrel who had a gain-of-function CYP2C19 allele than in those with other genotypes (11.9% versus 9.5%, p=0.022), according to the report, “but interaction between treatment and genotype groups was not significant for any type of major bleeding.”

The authors conclude, “The results of our study clearly show the absence of interaction between the occurrence of any CYP2C19 loss-of-function allele and the superiority of ticagrelor over clopidogrel for all efficacy events tested.”

Reference:

Effect of CYP2C19 and ABCB1 single nucleotide polymorphisms on outcomes of treatment with ticagrelor versus clopidogrel for acute coronary syndromes: a genetic substudy of the PLATO trial

Lancet 2010;