Clopidogrel Use and CYP2C19 Genotypes in Patients Undergoing Vascular Intervention Procedure: A Hospital-Based Study

Figures & data

Table 1 Distribution of Diplotype and Predicted Phenotype

Phenotype	Diplotype	Clopidogrel User (%)
Extensive metabolizer		1052 (39.2)
	*1/*1	1052 (100)
Intermediate metabolizer		1235 (46.0)
	*1/*2	1074 (87.0)
	*1/*3	161 (13.0)
Poor metabolizer		400 (14.9)
	*2/*2	285 (71.3)
	*2/*3	99 (24.8)
	*2/*6	6 (1.5)
	*3/*3	5 (1.3)
	Novel^a	5 (1.3)

Notes: ^anovel phenotype: 1 with rs4244285 (*2); rs4986893 (*3); rs72552267 (*6); 4 with rs4244285 (*2) homozygous and rs72552267 (*6) heterozygous.

Figure 1 Flow diagram of the participant recruitment process in this study.

Abbreviations: EM, extensive metabolizer; IM, intermediate metabolizer; PM, poor metabolizer.

Table 2 Baseline Characteristics of Clopidogrel Users by CYP2C19 Phenotypes

	Total (n = 2,87)	CYP2C19 Phenotype		p-value
		PM (n = 400, 14.9%)	Non-PM^b (n = 2287, 85.1%)
Age^a	62 (54–70)	63 (54–70)	62 (54–70)	0.437
Male	1912 (71.2%)	269 (67.3%)	1643 (71.8%)	0.070
Medical department^a				0.419
Cardiology	1728 (64.3%)	258 (64.5%)	1470 (64.3%)
Neurology	447 (16.6%)	77 (19.3%)	370 (16.2%)
Vascular surgery	136 (5.1%)	17 (4.3%)	119 (5.2%)
Rheumatology	98 (3.7%)	12 (3.0%)	86 (3.8%)
Other	278 (10.4%)	36 (9.0%)	242 (10.6%)
Antiplatelet therapy				0.708
Single	1141 (42.5%)	177 (44.3%)	964 (42.2%)
DAPT	1482 (55.2%)	213 (53.3%)	1269 (55.5%)
TAPT	64 (2.4%)	10 (2.5%)	54 (2.4%)
Comorbidities
Heart disease	2228 (82.9%)	325 (81.3%)	1903 (83.2%)	0.374
Hypertension	2071 (77.1%)	314 (78.5%)	1757 (76.8%)	0.503
Diabetes mellitus	1407 (52.4%)	214 (53.5%)	1193 (52.2%)	0.661
Hyperlipidemia	2001 (74.5%)	298 (74.5%)	1703 (74.5%)	1.000
CIHD	1861 (69.3%)	278 (69.5%)	1583 (69.2%)	0.957
Stroke	554 (20.6%)	94 (23.5%)	460 (20.1%)	0.140

Notes: Data are presented as number and percentage. ^aAge and medical department where clopidogrel was first prescribed. ^bNon-PM group includes IM and EM.

Abbreviations: DAPT, dual antiplatelet therapy; TAPT, triple antiplatelet therapy; CIHD, chronic ischemic heart disease.

Table 3 Factors Associated with Acute Myocardial Infarction and Stroke in 2687 Participants Who Were Prescribed Clopidogrel

	Univariate		Multivariate
	OR (95% CI)	p-value	OR (95% CI)	p-value
CYP2C19 phenotype (PM vs non-PM^a)	1.26 (0.80–1.99) 1.00 (0.98–1.01)	0.314
Age, years		0.667
Sex (male vs female)	1.25 (0.84–1.87)	0.270
Hypertension	3.15 (1.73–5.74)	<0.001	2.26 (1.22–4.17)	0.009
Diabetes mellitus	1.99 (1.37–2.88)	<0.001	1.58 (1.08–2.31)	0.018
Hyperlipidemia	4.02 (2.16–7.49)	<0.001	3.36 (1.79–6.32)	<0.001
Chronic ischemic heart disease	1.44 (0.96–2.16)	0.079
Carotid angiography	2.11 (1.20–3.70)	0.009	2.21 (1.25–3.92)	0.007
Extremity angiography	1.74 (0.41–7.49)	0.455
PTCA	1.04 (0.62–1.73)	0.892

Notes: ^aNon-PM group includes intermediate metabolizers and extensive metabolizers.

Abbreviations: OR, odds ratio; CI, confidence interval; PTCA, percutaneous transluminal coronary angioplasty; PM, poor metabolizer.

Table 4 Cardiovascular Interventional Procedures of Clopidogrel Users by CYP2C19 Phenotypes

	Total (n = 1554)	CYP2C19 Phenotype		p-value
		PM (n = 236)	Non-PM^a (n = 1318)
Cardiac catheterization	1471 (94.7%)	222 (94.1%)	1249 (94.8%)	0.778
Number of cardiac catheterization	1 (1–2)	1 (1–2)	1 (1–2)	0.104
PTCA	1291 (87.8%)	201 (90.5%)	1090 (87.3%)	0.208
Coronary artery bypass graft	132 (8.49%)	14 (5.9%)	118 (9.0%)	0.160
Number of CABG	1 (1–1)	1 (1–1)	1 (1–1)	1.000
Carotid angiography	148 (9.5%)	26 (11.0%)	122 (9.3%)	0.467
Number of carotid angiography	1 (1–1)	1 (1–2)	1 (1–1)	0.010
Extremity angiography	22 (1.4%)	5 (2.1%)	17 (1.3%)	0.363
Number of extremity angiography	1 (1–1)	1 (1–1.5)	1 (1–1)	0.411

Notes: Data are presented as number and percentage or as median and interquartile range. ^anon-PM group includes IM and EM.

Abbreviations: PTCA, percutaneous transluminal coronary angioplasty; CABG, coronary artery bypass graft.

Table 5 Factors Associated with the Number of Carotid Angiography in Clopidogrel Users

	Univariate		Multivariate
	OR (95% CI)	p-value	OR (95% CI)	p-value
Phenotype (PM vs non-PM^a)	3.01 (1.20–7.54)	0.019	3.13 (1.19–8.22)	0.020
Age, years	0.96 (0.93–1.00)	0.037	0.97 (0.93–1.01)	0.117
Sex (male vs female)	1.08 (0.44–2.67)	0.863
Hypertension	1.27 (0.44–3.67)	0.656
Diabetes mellitus	1.45 (0.65–3.26)	0.365
Hyperlipidemia	0.62 (0.27–1.42)	0.261
Chronic ischemic heart disease	0.38 (0.17–0.87)	0.022	0.46 (0.19–1.09)	0.076

Notes: ^aNon-PM group includes intermediate metabolizers and extensive metabolizers.

Abbreviations: OR, odds ratio; CI, confidence interval; PM, poor metabolizer.

Figure 2 Comparison of the number of carotid angiographies in the CYP2C19 PM and non-PM groups.