Table 2. Overview of pharmacogenetic analysis populations by endpoint.
| Outcome | Endpoint Variable | Analysis Population | MAF* cut-off | STABILITY (n.event/n.total) | SOLID-TIMI 52 (n.event/n.total) | Meta-Analysis# (n.event/n.total) |
|---|---|---|---|---|---|---|
| Lp-PLA2 enzyme activity | Baseline | PGx subjects in placebo arm and darapladib treated arm | > 0% | 12640 | 9516 | 22156 |
| Change from baseline | PGx subjects in darapladib treated arm | > 0.5% | 6170 | 4704 | 10874 | |
| Efficacy | MCE | PGx subjects in placebo arm and darapladib treated arm | > 0.5% | Placebo:688/6863; Darapladib:585/6714 | Placebo:752/5201; Darapladib:733/5203 | Placebo:1440/12064; Darapladib:1318/11917 |
| MI (fatal + non-fatal) | PGx subjects in placebo arm and darapladib treated arm | > 0.5% | Placebo:358/6863; Darapladib:292/6714 | Placebo:475/5201; Darapladib:448/5203 | Placebo:833/12064; Darapladib:740/11917 | |
| Tolerability | Diarrhea§ | White PGx subjects with diarrhea event within 90 days of receiving darapladib, excluding subjects on Metformin | > 0.5% | Darapladib:235/3405 | Darapladib:246/3155 | Darapladib:481/6560 |
| MS diarrhea§ - Moderate and severe | White PGx subjects with diarrhea event within 90 days of receiving darapladib, excluding subjects on Metformin | > 0.5% | Darapladib:97/3267 | Darapladib:115/3024 | Darapladib:212/6291 | |
| Odor—Bathroom event | PGx subjects in darapladib treated arm | > 0.5% | Darapladib:735/6568 | Darapladib:548/5071 | Darapladib:1283/11639 | |
| Odor—Non-bathroom event | PGx subjects in darapladib treated arm | > 0.5% | Darapladib:340/6173 | Darapladib:244/4769 | Darapladib:584/10942 |
* MAF = Minor Allele Frequency; Analyses included imputed variants (imputation r2 ≥ 0.5) in both STABILITY and SOLID-TIMI 52 studies. Analysis of Lp-PLA2 enzyme activity was performed using 13,572,687 variants, whilst 9,334,585 variants were used for the efficacy and tolerability analyses
# Meta-analyses were done within placebo or darapladib treated arm separately.
§ In order to reduce a signal to noise ratio, the diarrhea endpoint was defined as a subset that was most likely associated to treatment with darapladib. For more details, see Material & Methods (Phenotype definition and measurements).
MI = Myocardial infarction; MCE = Major Coronary Event