Author + information
- Grant W. Reed,
- Christopher P. Cannon,
- Jill Waalen,
- Paul S. Teirstein,
- Jean–Francois Tanguay,
- Peter B. Berger,
- Eric J. Topol and
- Matthew J. Price
Cigarette smoking induces cytochrome P450 1A2, which metabolizes clopidogrel to its active form. The pharmacodynamic effect of smoking on platelet inhibition in patients with high on–treatment platelet reactivity (OTR) after percutaneous coronary intervention (PCI) is unknown.
Platelet reactivity was assessed in 5,427 patients of the Gauging Responsiveness With A VerifyNow P2Y12 Assay: Impact on Thrombosis and Safety (GRAVITAS) trial. VerifyNow P2Y12 Reaction Units (PRU) were obtained at 12–24 hours (baseline), 30 days, and 6 months after PCI. Patients were stratified by smoking status. Patients with high OTR (≥230 PRU) were randomized to clopidogrel 75 mg or 150 mg daily.
At baseline, smokers (n=971) had lower PRU than non–smokers (n=4,456) (183±91 PRU vs 207±93 PRU; p<0.001), and were less likely to have high OTR (31.9% vs 42.1%; p<0.001). In patients with high OTR randomized to clopidogrel 75 mg, smokers had significantly lower PRU than non–smokers over time. However, in patients on clopidogrel 150 mg, PRU was not significantly different between smokers and non–smokers over time. Smokers on clopidogrel 75 mg were also less likely to have high OTR, but no difference was observed in those on clopidogrel 150 mg (Table). Tests demonstrated an interaction between smoking and dosing strategy at 30 days (p=0.007) and 6 months (p=0.098).
In GRAVITAS, smokers had greater platelet inhibition on clopidogrel 75 mg, but this difference was eliminated with the 150 mg dose.
|Time||PRU||% High OTR||PRU||% High OTR||PRU||% High OTR|
|Clopidogrel 75 mg|
|30 days||224 ± 71||48%||254 ± 68||65%||<0.001||<0.001|
|6 months||217 ± 76||37%||247 ± 70||63%||<0.001||<0.001|
|Clopidogrel 150 mg|
|30 days||203 ± 78||35%||208 ± 74||41%||0.48||0.21|
|6 months||190 ± 79||30%||203 ± 80||37%||0.10||0.16|
Results reported as PRU mean ± standard deviation.
P-value for the comparison of smokers and non-smokers at each time point.
↵* Defined as smoking within the past 7 days.
Moderated Poster Contributions
Poster Sessions, Expo North
Monday, March 11, 2013, 9:45 a.m.–10:30 a.m.
Session Title: Adjunct Pharmacology
Abstract Category: 39. TCT@ACC–i2: Adjunct Pharmacology
Presentation Number: 2115M–219
- 2013 American College of Cardiology Foundation