Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 1620 Tremont Street, Boston, MA 02120, USA.
Circulation. 2009 Dec 8;120(23):2322-9. doi: 10.1161/CIRCULATIONAHA.109.873497. Epub 2009 Nov 23.
Recent studies have raised concerns about the reduced efficacy of clopidogrel when used concurrently with proton pump inhibitors (PPIs), but those studies may have overestimated the risk.
We studied the potential for increased risk of adverse cardiovascular events among users of clopidogrel with versus without concurrent use of PPIs in 3 large cohorts of patients > or =65 years of age, treated between 2001 and 2005. All patients had undergone percutaneous coronary intervention or had been hospitalized for acute coronary syndrome in Pennsylvania, New Jersey, or British Columbia, and subsequently had initiated treatment with clopidogrel. We recorded myocardial infarction hospitalization, death, and revascularization among PPI users and nonusers. We assessed our primary end point of myocardial infarction hospitalization or death using cohort-specific and pooled regression analyses. We entered 18 565 clopidogrel users into our analysis. On a pooled basis, 2.6% of those who also initiated a PPI versus 2.1% of PPI nonusers had a myocardial infarction hospitalization; 1.5% versus 0.9% died; and 3.4% versus 3.1% underwent revascularization. The propensity score-adjusted rate ratio for the primary end point of myocardial infarction or death was 1.22 (95% confidence interval, 0.99 to 1.51); for death, 1.20 (95% confidence interval, 0.84 to 1.70); and for revascularization, 0.97 (95% confidence interval, 0.79 to 1.21). Matched analyses generally yielded similar results.
Although point estimates indicated a slightly increased risk of myocardial infarction hospitalization or death in older patients initiating both clopidogrel and a PPI, we did not observe conclusive evidence of a clopidogrel-PPI interaction of major clinical relevance. Our data suggest that if this effect exists, it is unlikely to exceed a 20% risk increase.
最近的研究对氯吡格雷与质子泵抑制剂 (PPI) 同时使用时疗效降低表示担忧，但这些研究可能高估了风险。
我们在宾夕法尼亚州、新泽西州和不列颠哥伦比亚省接受过经皮冠状动脉介入治疗或因急性冠状动脉综合征住院治疗的 3 个大型年龄 ≥ 65 岁患者队列中，研究了氯吡格雷使用者与非使用者同时使用 PPI 是否会增加不良心血管事件的风险。所有患者均开始使用氯吡格雷治疗。我们记录了 PPI 使用者和非使用者的心肌梗死住院、死亡和血运重建情况。我们使用队列特异性和汇总回归分析评估了我们的主要终点心肌梗死住院或死亡。我们将 18565 例氯吡格雷使用者纳入分析。总体而言，开始使用 PPI 的患者中有 2.6%发生心肌梗死住院，而未使用 PPI 的患者中有 2.1%；1.5%的患者死亡，而 0.9%的患者死亡；3.4%的患者进行血运重建，而 3.1%的患者进行血运重建。主要终点心肌梗死或死亡的倾向评分调整后率比为 1.22（95%置信区间，0.99 至 1.51）；死亡率为 1.20（95%置信区间，0.84 至 1.70）；血运重建率为 0.97（95%置信区间，0.79 至 1.21）。匹配分析的结果大致相同。
尽管点估计表明，开始同时使用氯吡格雷和 PPI 的老年患者发生心肌梗死住院或死亡的风险略有增加，但我们没有观察到氯吡格雷-PPI 相互作用具有重要临床意义的确凿证据。我们的数据表明，如果这种影响确实存在，其风险增加也不太可能超过 20%。
