Department of Pharmacology, Clinical Research Unit, APHP, St. Antoine Hospital, UMPC-Paris 06 University, 27 Rue Chaligny, Paris, France.
Circulation. 2011 Feb 8;123(5):474-82. doi: 10.1161/CIRCULATIONAHA.110.965640. Epub 2011 Jan 24.
Clopidogrel requires metabolic activation by cytochrome P450 2C19 (CYP2C19). Proton pump inhibitors (PPIs) that inhibit CYP2C19 are commonly coadministered with clopidogrel to reduce the risk of gastrointestinal bleeding. This analysis compares treatment outcomes for patients in the French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) who did or did not receive clopidogrel and/or PPIs.
The FAST-MI registry included 3670 patients (2744 clopidogrel- and PPI-naïve patients) presenting with definite MI. Patients were categorized according to use of clopidogrel and/or PPI within 48 hours after hospital admission. PPI use was not associated with an increased risk for any of the main in-hospital events (in-hospital survival, reinfarction, stroke, bleeding, and transfusion). Likewise, PPI treatment was not an independent predictor of 1-year survival (hazard ratio, 0.97; 95% confidence interval [CI], 0.87 to 1.08; P=0.57) or 1-year MI, stroke, or death (hazard ratio, 0.98; 95% CI, 0.90 to 1.08; P=0.72). No differences were seen when the type of PPI or CYP2C19 genotype was taken into account. In the propensity-matched cohorts, the odds ratios for major in-hospital events in PPI versus no PPI were 0.29 (95% CI, 0.06 to 1.44) and 1.70 (95% CI, 0.10 to 30.3) for patients with 1 and 2 variant alleles, respectively. Similarly, the hazard ratio for 1-year events in hospital survivors was 0.68 (95% CI, 0.26 to 1.79) and 0.55 (95% CI, 0.06 to 5.30), respectively.
PPI use was not associated with an increased risk of cardiovascular events or mortality in patients administered clopidogrel for recent MI, whatever the CYP2C19 genotype, although harm could not be formally excluded in patients with 2 loss-of-function alleles.
氯吡格雷需要细胞色素 P450 2C19（CYP2C19）代谢激活。质子泵抑制剂（PPIs）抑制 CYP2C19，常与氯吡格雷联合用于降低胃肠道出血风险。本分析比较了法国急性 ST 段抬高和非 ST 段抬高心肌梗死（FAST-MI）注册登记中接受或未接受氯吡格雷和/或 PPI 治疗的患者的治疗结局。
FAST-MI 登记包括 3670 例（2744 例氯吡格雷和 PPI 初治患者）确诊为 MI 的患者。患者根据入院后 48 小时内是否使用氯吡格雷和/或 PPI 进行分类。PPI 治疗并未增加任何主要院内事件（院内生存率、再梗死、卒中和出血及输血）的风险。同样，PPI 治疗也不是 1 年生存率（危险比，0.97；95%置信区间[CI]，0.87 至 1.08；P=0.57）或 1 年 MI、卒中和死亡（危险比，0.98；95% CI，0.90 至 1.08；P=0.72）的独立预测因素。当考虑 PPI 的类型或 CYP2C19 基因型时，未观察到差异。在倾向匹配的队列中，PPI 与无 PPI 相比，院内主要不良事件的比值比分别为 0.29（95%CI，0.06 至 1.44）和 1.70（95%CI，0.10 至 30.3），用于 1 个和 2 个变异等位基因的患者。同样，在幸存患者中，1 年院内事件的危险比分别为 0.68（95%CI，0.26 至 1.79）和 0.55（95%CI，0.06 至 5.30）。
在接受氯吡格雷治疗近期 MI 的患者中，无论 CYP2C19 基因型如何，PPI 的使用与心血管事件或死亡率增加无关，但不能排除在具有 2 个失活等位基因的患者中存在危害。
