Author + information
- Derek Yiu Fai So,
- George Wells,
- Ruth McPherson,
- Marino Labinaz,
- Chris Glover,
- Michel Le May,
- Alexander Dick,
- Michael Froeschl,
- Jean-Francois Marquis,
- Nitan Garg,
- Jordan Bernick,
- Luan Tran,
- Benjamin Hibbert and
- Jason Roberts
Patients with common at-risk genetic variants have increased MACE following percutaneous coronary intervention (PCI). Ultra rapid genotyping may facilitate a pharmacogenomic approach to anti-platelet therapy in STEMI patients receiving PCI.
We utilized a point-of-care genetic device, designed to identify CYP2C19*2, ABCB1 3435 C and CYP2C19*17 carriers, to evaluate the potential of a pharmacogenomic strategy in STEMI patients. Following successful PCI, CYP2C19*2 carriers and ABCB1 3435 TT homozygotes were randomized to a strategy of prasugrel 10mg daily for 1 month or clopidogrel 150mg daily for 7 days then 75mg daily for 3 weeks. The primary endpoint is the proportion of CYP2C19*2 and/or ABCB1 3435 TT carriers with high on-treatment platelet reactivity (HPR) (defined by P2Y12 reactivity unit (PRU) >234) in the prasugrel compared to the clopidogrel arm at 1 month.
Among 102 patients, 59 (57.8%) were randomized following identification of at least one at-risk genotype. Overall, 36.3% and 32.3% were CYP2C19*2 and ABCB1 3435 TT carriers, respectively. The baseline PRU was 183.5±90.6 among carriers compared with 147.3±84.7 in non-carriers, p=0.04. Primary and secondary outcomes are shown below:
|Patients without at-risk genetic variants (N=43)||At-risk patients randomized to Prasugrel (N=30)||At-risk patients randomized to High-dose Clopidogrel (N=29)||p-value†|
|Patients with PRU>234 at Day 30 - no.(%)||2 (4.7)||0 (0)||7 (24.1)||0.005|
|Patients with PRU>208 at Day 30 - no.(%)||4 (9.3)||1 (3.3)||10 (34.5)||0.003|
|PRU at Day 30||110.4±85.1||53.8±60.3||157.1±94.7||<0.001|
|% Platelet Inhibition at Day 30||59.6±28.5||80.0±21.6||42.3±31.9||<0.001|
Plus-minus values are mean ±SD, PRU = P2Y12 Reactivity Unit
↵† - p-values between patients randomized to prasugrel vs. high-dose clopidogrel
Point-of-care genetic testing permitted rapid identification of STEMI patients with an increased propensity for HPR. Alteration to prasugrel in carriers of at-risk genetic variants decreased HPR compared to a strategy of high-dose clopidogrel.
West, Room 3001
Saturday, March 09, 2013, 9:00 a.m.-9:15 a.m.
Session Title: ACS: New Agents and Approaches
Abstract Category: 3. Acute Coronary Syndromes: Therapy
Presentation Number: 901-7
- 2013 American College of Cardiology Foundation