Table 2.
The investigated outcomes according to CYP2C19 genotype (Any LOF allele vs no LOF allele)
| Author | MACE | MI | Revascularization | Stroke | Definite stent thrombosis | Bleeding | High platelet reactivity3 | Platelet reactivity4 |
|---|---|---|---|---|---|---|---|---|
| Tantry [25] | – | – | – | – | – | – | – | No statistical influence (data shown below) |
| Wallentin [14] | 115/1384 (8.3%) vs 296/3554 (8.3%) | 102/1384 (7.4%) vs 273/3554 (7.7%)1 | – | 13/1384 (0.9%) vs 23/3554 (0.6%) | 15/943 (1.5%) vs 22/2341 (1.0%) | 149/1380 (10.8%) vs 331/3547 (9.3%) | – | – |
| Stimpfle [26] | – | – | – | – | – | – | – | 12.27 ± 11.4 vs 11.21 ± 7.0 AU*min |
| Dong [27] | 13/38 (34.2%) vs 6/26 (23.1%) | 3/38 (7.9%) vs 1/26 (3.8%) | 3/38 (7.9%) vs 2/26 (7.7%) | 4/38 (10.5%) vs 2/26 (7.7%) | – | – | – | – |
| Wang [11] | 16/184(8.7%) vs 4/137 (2.9%) | – | – | 15/184(8.2%) vs 4/137 (2.9%) | – | 6/184 (3.3%) vs 6/137 (4.4%)2 | 17/157(10.8%) vs 16/118 (13.6%) | – |
| Yu [12] | 23/202(11.4%) vs 7/45(15.6%) | 0/202(0%) vs 0/45(0%) | – | 0/202(0%) vs 0/45(0%) | 0/202(0%) vs 0/45(0%) | 27/202(13.4%) vs 16/45(35.6%) | – | – |
| Machal [28] | – | – | – | – | – | – | – | 342 ± 267.2 vs 405 ± 385.2; 203 ± 64.5 vs 207 ± 96.3 AU*min |
| Zhang [13] | 12/302(4.0%) vs 6/138(4.3%) | 1/302(0.3%) vs 3/138(2.2%) | 10/302(3.3%) vs 6/138(4.3%) | 1/302(0.3%) vs 0/138(0%) | 2/302(0.7%) vs 3/138(2.2%) | 5/302(1.7%) vs 4/138(2.9%) | – | – |
1: This result specifically included both cardiac death and myocardial infarction
2: This result specifically included both major and minor bleeding events
3: High platelet reactivity = P2Y12 reaction units of more than 208, as measured the VerifyNow P2Y12 assay
4: As methods of platelet reactivity assessment in these three studies were all different, we didn’t include these data for meta-analysis
Firstly, there were three methods of platelet reactivity assessment in Tantry’s study, including aggregometry, VerifyNow P2Y12 and vasodilator-stimulated phosphoprotein-phosphorylation (VASP) assay. All the methods were evaluated at 8 h postloading (A) and during maintenance phases (2 to 6 weeks, 8 h after the last dose) (B). The specify data and P value of LOF and no LOF groups at two timepoints were as follows respectively:
(i) 5 umol/L ADP-induced platelet aggregation (%): 19.94 ± 8.86 vs 18.10 ± 11.65, P = 0.518; 22.08 ± 10.93 vs 21.09 ± 12.00, P = 0.88
(ii) 20 umol/L ADP-induced platelet aggregation (%): 28.06 ± 9.85 vs 26.32 ± 12.61, P = 0.529; 29.01 ± 12.81 vs 29.01 ± 14.04, P = 0.803
(iii) P2Y12 Reaction Units: 41.19 ± 57.14 vs 43.04 ± 43.60, P = 0.301; 51.67 ± 52.56 vs 42.32 ± 36.97, P = 0.898
(iv) VASP-PRI (%): 24.16 ± 19.73 vs 20.10 ± 13.67, P = 0.616; 21.88 ± 15.11 vs 20.90 ± 16.02, P = 0.878
Secondly, the result of Stimpfle’s study was determined at earliest 2 h after loading (median 12 h) 180 mg of ticagrelor, while these results of Machal’s study were determined at 1 h after the first administration of ticagrelor and repeated after 24 h. Although both studies used the same method of Multiplate® analyzer (Roche), there was a big difference in values
MACEs major adverse cardiovascular events, MI myocardial infarction