Background
Methods
Study populations
Platelet aggregation
Genotyping
Clinical outcomes
Statistical analysis
Results
Incidence of END
Patients with END (n = 95) | Patients without END (n = 280) | p value | |
---|---|---|---|
CYP2C8 (rs17110453) | |||
AA | 43 (45.3) | 132 (47.1) | 0.751 |
AC + CC | 52 (54.7) | 148 (52.9) | |
CYP2C8 (rs1934980) | |||
CC | 15 (15.8) | 40 (14.3) | 0. 723 |
CT + TT | 80 (84.2) | 240 (85.7) | |
CYP2C9 (rs1799853) | |||
CC | 95 (100) | 280 (100) | – |
CYP2C9 (rs1057910) | |||
AA | 85 (89.5) | 245 (87.5) | 0.626 |
AC + CC | 10 (10.5) | 35 (12.5) | |
CYP3A4(rs2242480) | |||
CC | 51 (53.7) | 155 (55.4) | 0.786 |
TT + CT | 44 (46.3) | 125 (44.6) | |
ABCB1(rs2032562) | |||
GG | 25 (26.3) | 65 (23.2) | 0.532 |
TT + GT | 70 (73.7) | 215 (76.8) | |
P2Y1(rs701265) | |||
AA | 46 (48.4) | 158 (56.4) | 0.193 |
AG + GG | 49 (51.6) | 122 (43.6) | |
P2Y1(rs1439010) | |||
AA | 48 (50.5) | 156 (55.7) | 0.402 |
AG + GG | 47 (49.5) | 124 (44.3) | |
P2Y1(rs1371097) | |||
CC | 45 (47.4) | 161 (57.5) | 0.096 |
TT + CT | 50 (52.6) | 119 (42.5) | |
CYP3A5(rs776746) | |||
AA | 12 (12.6) | 36 (12.9) | 0.998 |
GG + AG | 83 (87.4) | 244 (87.1) | |
CYP2C19(rs4244285) | |||
GG | 20 (16.8) | 133 (47.5) | < 0.001 |
AG + AA | 75 (78.9) | 147 (52.5) | |
CYP2C19(rs4986893) | |||
GG | 86 (90.5) | 262 (93.6) | 0.752 |
AG | 9 (9.5) | 18 (6.4) | |
P2Y12(rs16863323) | |||
CC | 16 (16.8) | 62 (22.1) | 0.276 |
TT + CT | 79 (83.2) | 218 (77.9) | |
P2Y12(rs9859538) | |||
GG | 68 (71.6) | 206 (73.6) | 0.705 |
AG + AA | 27 (28.4) | 74 (26.4) | |
GPIIIa (rs2317676) | |||
AA | 62 (65.3) | 188 (67.1) | 0.724 |
AG + GG | 33 (34.7) | 92 (32.9) | |
GPIIIa (rs11871251) | |||
AA | 27 (28.4) | 86 (30.7) | 0.678 |
AG + GG | 68 (71.6) | 194 (69.3) |
Best modela | Training balanced accuracy | Testing balanced accuracy | Cross-validation consistency | Sign test (P value) |
---|---|---|---|---|
16 | 0.613 | 0.582 | 7/10 | 6 (0.432) |
1,2 | 0.418 | 0.534 | 8/10 | 8 (0.296) |
1, 2, 3 | 0.612 | 0.623 | 10/10 | 9 (0.019) |
1, 2, 3, 4 | 0.513 | 0.586 | 8/10 | 6 (0.632) |
1, 2, 3, 4, 5 | 0.617 | 0.522 | 9/10 | 8 (0.763) |
1, 2, 3, 4, 5, 6 | 0.543 | 0.514 | 7/10 | 7 (0.604) |
1, 2, 3, 4, 5, 6, 7 | 0.476 | 0.495 | 6/10 | 5 (0.835) |
1, 2, 3, 4, 5, 6, 7, 8 | 0.543 | 0.566 | 7/10 | 7 (0.351) |
1, 2, 3, 4, 5, 6, 7, 8, 9 | 0.446 | 0.552 | 8/10 | 5 (0.675) |
1, 2, 3, 4, 5, 6, 7, 8, 9, 10 | 0.612 | 0.624 | 6/10 | 6 (0.723) |
1, 2, 3, 4, 5, 6, 7, 8, 9, 10,11 | 0.575 | 0.513 | 7/10 | 7 (0.372) |
1, 2, 3, 4, 5, 6, 7, 8, 9, 10,11,12 | 0.484 | 0.497 | 5/10 | 6 (0.667) |
1, 2,3, 4, 5, 6, 7, 8, 9, 10,11,12,13 | 0.597 | 0.583 | 7/10 | 5 (0.432) |
1, 2, 3, 4, 5, 6, 7, 8, 9, 10,11,12,13,14 | 0.582 | 0.605 | 8/10 | 6 (0.317) |
1, 2, 3, 4, 5, 6, 7, 8, 9, 10,11,12,13,14,15 | 0.622 | 0.572 | 6/10 | 8 (0.186) |
1, 2, 3, 4, 5, 6, 7, 8, 9, 10,11,12,13,14,15,16 | 0.475 | 0.402 | 4/10 | 5 (0.726) |
Association of SNPs in clopidogrel-relevant genes with END
Gene-gene interactions and END
rs4244285 | GG | AA | AA | AA | AG | AA, AG | AA | AA, AG |
---|---|---|---|---|---|---|---|---|
rs16863323 | CC | TT | TT | CT | CT | TT | TT, CT | TT, CT |
rs2317676 | AA | GG | AG, GG | AG | AG | GG | GG | GG, AG |
OR | 1 a | 2.72 | 1.93 | 2.38 | 1.32 | 1.14 | 1.05 | 1.07 |
95% CI | – | 1.16–6.76 | 1.04–4.12 | 1.12–5.54 | 0.68–2.12 | 0.72–1.87 | 0.86–2.53 | 0.66–1.95 |
P value | – | 0.007 | 0.037 | 0.026 | 0.434 | 0.325 | 0.482 | 0.583 |
High-risk interactive genotypes, platelet aggregation, and clinical outcomes
patients carrying the high-risk interactive genotypes (n = 87) | patients carrying the low-risk interactive genotypes (n = 288) | p value | |
---|---|---|---|
AA-induced platelet aggregation (%) | |||
before clopidogrel | 85.3 ± 14.8 | 71.2 ± 17.4 | < 0.001 |
after 7–10 days clopidogrel | 55.5 ± 12.6 | 35.3 ± 14.9 | < 0.001 |
inhibition | 30.2 ± 9.2 | 38.1 ± 11.4 | < 0.001 |
ADP-inducedplatelet aggregation (%) | |||
Before clopidogrel | 79.1 ± 16.2 | 67.9 ± 14.8 | < 0.001 |
after 7–10 days clopidogrel | 45.2 ± 13.2 | 25.6 ± 8.6 | < 0.001 |
inhibition | 34.9 ± 12.3 | 46.4 ± 13.6 | < 0.001 |
END (n, %) | 34 (39.1) | 61 (21.2) | < 0.001 |
RIS (n, %) | 1 (1.1) | 2 (0.7) | 0.963 |
MI (n, %) | 0 (0.0) | 1 (0.3) | 0.586 |
Death (n, %) | 1 (1.1) | 1 (0.3) | 0.754 |
Safety outcomes | |||
Asymptomatic HT (n, %) | 1 (1.1) | 6 (2.1) | 0.438 |
Asymptomatic ICH (n, %) | 1 (1.1) | 1 (0.3) | 0.754 |
Extracranial bleeding (n, %) | 2 (2.3) | 9 (3.1) | 0.443 |
Cox proportional-hazards model analysis for END
Factor | HR | 95% CI | P value |
---|---|---|---|
Age | 0.82 | 0.59–1.28 | 0.476 |
Diabetes mellitus | 1.67 | 0.92–2.13 | 0.135 |
Hemoglobin A1C | 1.08 | 0.88–2.36 | 0.198 |
Fasting blood glucose | 0.97 | 0.82–1.86 | 0.395 |
AA-induced platelet aggregation | 0.73 | 0.72–1.69 | 0.512 |
ADP-induced platelet aggregation | 0.78 | 0.76–1.83 | 0.438 |
CYP2C19rs4244285AA/AG | 2.41 | 1.27–6.82 | 0.005 |
High-risk interactive variable | 2.82 | 1.36–7.76 | 0.003 |