Author + information
- Karin Badavievich Mirzaev1,
- Eric Rytkin1,
- Elena Anatolyevna Grishina1,
- Valery Valeryevich Smirnov2,
- Kristina Anatolyevna Ryzhikova1,
- Zhannet Alimovna Sozaeva1,
- Denis Anatolyevich Andreev3 and
- Dmitrij Alekseevitch Sychev1
CYP2C19, ABCB1 loss-of-function variant carriers are subject to diminished platelet response to clopidogrel. This may result in complications associated with suboptimal blood-thinning levels, such as stent thrombosis as well as other major adverse cardiovascular events. The purpose of this study was to assess the impact of CYP2C19, ABCB1 genes polymorphisms and CYP3A4 isoenzyme activity on the incidence of stent implantation complications for patients with an acute coronary syndrome.
Seventy-six patients (median age 63, range 37 to 91 years) with an acute coronary syndrome who underwent percutaneous coronary intervention and had either drug-eluting stent (n=30) or bare-metal stent (n=46) implanted, were screened for CYP2C19, ABCB1 genes polymorphisms: CYP2C19*2, CYP2C19*3, CYP2C19*17, ABCB1 3435 CT, ABCB1 3435 TT. CYP3A4 isoenzyme activity was determined by urine cortisol and 6-beta-hydroxycortisol levels. P2Y12 reaction unit levels utilizing VerifyNow P2Y12 assay (Accumetrics, San Diego, CA) were measured. Such stent implantation complications as stent thrombosis (n=2) and restenosis (n=1) were observed among drug-eluting stent recipients.
Low mean 6-beta-hydroxycortisol / cortisol ratio is indicative of impaired CYP3A4 activity and was associated with higher risk of thrombosis (β coefficient=0.022, SE 0.009, p=0.021 in the linear regression model). The increase in the length of the implanted stent was associated with higher risk of restenosis (β coefficient=0.006, SE=0.002, p=0.001 in the linear regression model). The presence of the CYP2C19*2 polymorphism did not affect the incidence of stent thrombosis (β coefficient=-1.626, SE=1.449, p=0.262 in the logistic regression model), nor did the CYP2C19*17 (β coefficient=-0.907, SE=1.438, p=0.528 in the logistic regression model) and ABCB1 3435 polymorphisms (β coefficient=1.270, SE=1.442, p=0.378 in the logistic regression model).
Although it is accepted that CYP2C19, and ABCB1 loss-of-function variant carriers may need clopidogrel dose adjustment or drug change, we did not find evidence that the presence of CYP2C19*2, CYP2C19*17, ABCB1 3435 CT, ABCB1 3435 TT polymorphisms may jeopardize the safety of stent implantation in patients with an acute coronary syndrome. Patients with low CYP3A4 isoenzyme activity may have increased risk of stent thrombosis and this matter needs further investigation.