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

{{CMG}}; '''Associate Editor(s)-In-Chief:''' [[Priyamvada Singh|Priyamvada Singh, M.B.B.S.]] [mailto:psingh13579@gmail.com]

==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 <ref name="pmid22088980">{{cite journal| author=Mega JL, Hochholzer W, Frelinger AL, Kluk MJ, Angiolillo DJ, Kereiakes DJ et al.| title=Dosing clopidogrel based on CYP2C19 genotype and the effect on platelet reactivity in patients with stable cardiovascular disease. | journal=JAMA | year= 2011 | volume= 306 | issue= 20 | pages= 2221-8 | pmid=22088980 | doi=10.1001/jama.2011.1703 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22088980  }} </ref> ==

* '''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.

==References==
{{Reflist|2}}

[[Category:Cardiology]]


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