Table 2.
Occurrence of thrombotic and bleeding events in CYP2C9 LoF carriers and noncarriers treated with clopidogrel
| Event | CYP2C9 LoF carriers [N = 352] (%) | Poor metabolizers [n = 42] (%) | Intermediate metabolizers [n = 310] (%) | CYP2C9 LoF noncarriers [N = 526] (%) | HR (CI)a | p value |
|---|---|---|---|---|---|---|
| Composite of thrombotic outcomes | 22 (6.3) | 4 (9.5) | 18 (5.8) | 31 (5.9) | 1.16 (0.67–2.02) | 0.60 |
| All-cause death | 13 (3.7) | 1 (2.4) | 12 (3.9) | 12 (2.3) | 1.82 (0.82–4.03) | 0.14 |
| Cardiovascular death | 5 (1.4) | 0 (0) | 5 (1.6) | 6 (1.1) | 1.36 (0.41–4.51) | 0.61 |
| MI | 14 (4.0) | 4 (9.5) | 10 (3.2) | 22 (4.2) | 1.05 (0.53–2.06) | 0.90 |
| TVR | 4 (1.1) | 1 (2.4) | 3 (1.0) | 4 (0.8) | 1.58 (0.39–6.40) | 0.53 |
| ST | 1 (0.3) | 1 (2.4) | 0 (0.0) | 1 (0.2) | 1.35 (0.09–21.65) | 0.83 |
| Stroke | 4 (1.1) | 0 (0.0) | 4 (1.3) | 4 (0.8) | 1.61 (0.40–6.56) | 0.51 |
| Bleeding outcomes | ||||||
| BARC 2–5 bleeding | 44 (12.5) | 5 (11.9) | 39 (12.6) | 78 (14.8) | 0.90 (0.62–1.30) | 0.57 |
| BARC 3 or 5 bleeding | 13 (3.7) | 1 (2.4) | 12 (3.9) | 20 (3.8) | 1.08 (0.53–2.19) | 0.83 |
| PLATO minor or major bleeding | 40 (11.4) | 5 (11.9) | 35 (11.3) | 73 (13.9) | 0.86 (0.58–1.27) | 0.45 |
| PLATO major bleeding | 10 (2.8) | 1 (2.4) | 9 (2.9) | 17 (3.2) | 0.93 (0.42–2.05) | 0.86 |
The event rates for poor (*2/*2, *2/*3 or *3/*3) and intermediate (*1/*2 or *1/*3) metabolizers are also shown. Differences in event rates for both poor and intermediate metabolizers were compared with CYP2C9 LoF noncarriers using Cox proportional hazard models. All comparisons were not statistically different (p value > 0.05).
BARC Bleeding Academic Research Consortium, CI confidence interval, CYP cytochrome P450, HR hazard ratio, LoF loss-of-function, MI myocardial infarction, PLATO PLATelet inhibition and patient Outcomes, ST stent thrombosis, TVR target vessel revascularization
aHRs are calculated by comparing CYP2C9 LoF carriers with noncarriers. The composite of thrombotic outcomes consists of cardiovascular death, MI and stroke. HRs were adjusted for CYP2C19 LoF allele carrier status and diagnosis at discharge