Experimental Anti-clotting Drug Brilinta Needs No Genetic Testing, Unlike Plavix

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Main Category: Cardiovascular / Cardiology
Also Included In: Heart Disease;  Blood / Hematology;  Genetics
Article Date: 29 Aug 2010 - 12:00 PDT

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Experimental anti-clotting medication Brilinta (ticagrelor) works on patients, regardless of whether they had the genetic variability that has been previously shown to affect a patients' responses to Plavix (clopidogrel), Sanofi-Aventis' blockbuster medication, AztraZeneca PLC announced today. An extensive study demonstrated that Brilinta eliminated the need for genetic testing for patients with acute coronary syndromes (ACS).

ACS (acute coronary syndromes) is an umbrella term which covers any group of clinical symptoms compatible with acute myocardial ischemia. It includes any condition brought on by sudden, reduced blood flow to the heart, which often causes chest pains (felt during a heart attack, or chest pain felt when at rest or doing physical activity - unstable angina). Acute coronary syndrome is generally diagnosed in the emergency department of a hospital.

The current medication for ACS - Plavix - requires a genetic test to find out whether the patient will respond properly to the drug. Brilinta does not need this genetic test, according to the Brilinta trial involving 18,624 patients.

A substudy of the trial, called PLATO (A Study of PLATelet Inhibition and Patient Outcomes), demonstrated that the effects on a combined primary endpoint of cardiovascular death, myocardial infarction, or stroke seen in ACS patients who received oral antiplatelet treatment, Brilinta, were maintained, regardless of their genetic variability.

AstraZeneca informs that PLATO is the first study to look at both efficacy and bleeding endpoints of patients with ACS treated with ticagrelor (Brilinta) who carry variations in the CYP2C19 and ABCB1 genes.

Details of the trial were presented at the European Society of Cardiology Congress, Stockholm, Sweden. It if also published in the peer-reviewed medical journal The Lancet.

CYP2C19 - regardless of the CYP2C19 genotype, the primary outcome occurred less frequently with ticagrelor compared to clopidogrel (interaction p=0.46). Ticagrelor event rates were 8.6% annually in carriers and 8.8% annually in non-carriers of CYP2C19 loss-of-function genotype. For clopidogrel patients that carried the CYP2C19 loss-of-function allele, there was a 11.2% per year event rate, compared to 10.0% per year for patients without the loss-of-function allele. Similar to the overall PLATO study, total major bleeding did not significantly differ between ticagrelor and clopidogrel regardless of CYP2C19 genotype.

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.

Professor Lars Wallentin, lead investigator of the PLATO genetic substudy and Professor of Cardiology and Research Director at the Uppsala University, Sweden, said:

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.

The substudy's aim was to determine 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.

"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"
Prof Lars Wallentin MD a Corresponding AuthorEmail Address, Stefan James MD a, Robert F Storey MD b, Martin Armstrong PhD c, Bryan J Barratt PhD c, Jay Horrow MD c, Steen Husted MD d, Prof Hugo Katus MD e, Prof P Gabriel Steg MD f g h, Svati H Shah MD i, Prof Richard C Becker MD i, for the PLATO investigators
The Lancet, Early Online Publication, 29 August 2010
doi:10.1016/S0140-6736(10)61274-3

Written by Christian Nrodqvist


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