Clopidogrel dosing and role of genetics: ELEVATE-TIMI 56 trial

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Priyamvada Singh, M.B.B.S. [2]

Overview

The results of the ELEVATE-TIMI 56 trial were recently presented in AHA November 2011 held at Orlando, Florida. The multicentric randomized double blinded trial was able to show that increasing the maintenance doses of clopidogrel to 225 mg daily in CYP2C19 heterozygotes patients with stable cardiovascular diseases, were able to cause similar levels of platelet reactivity as seen with the standard 75-mg dose in non-carriers. However, in patients who were homozygotes for CYP2C19 genes, doses as high as 300 mg daily did not result in comparable degrees of platelet inhibition.

ELEVATE-TIMI 56 trial

• Hypothesis - To assess whether increasing the dose of clopidogrel to 300 mg / day rather than the standard 75 mg / day maintenance dose improves outcomes in patients with loss-of-function CYP2C19 genotypes.

• Study design - Multicenter, randomized, double-blind trial

• Duration of study - 1 years

• Intervention - Maintenance doses of clopidogrel for 4 treatment periods, (each treatment period lasted 14 days). 247 noncarriers received 75 and 150 mg daily of clopidogrel (2 periods each), and 86 carriers (80 heterozygotes, 6 homozygotes) received 75, 150, 225, and 300 mg daily.

• Primary end point - Platelet function test results and adverse events.

• Conclusions - Increasing the maintenance doses of clopidogrel to 225 mg daily in CYP2C19 heterozygotes patients with stable cardiovascular diseases, were able to cause similar levels of platelet reactivity as seen with the standard 75-mg dose in non-carriers. However, in patients who were homozygotes for CYP2C19 genes, doses as high as 300 mg daily did not result in comparable degrees of platelet inhibition.