质子泵抑制剂的使用与氯吡格雷和替格瑞洛对心血管结局的影响的相关性：来自血小板抑制和患者结局试验的见解。
Association of proton pump inhibitor use on cardiovascular outcomes with clopidogrel and ticagrelor: insights from the platelet inhibition and patient outcomes trial.
机构信息
MSc, Division of Cardiology, St. Michael's Hospital, 30 Bond St, Room 6-034, Queen, Toronto, Ontario, Canada M5B 1W8.
出版信息
Circulation. 2012 Feb 28;125(8):978-86. doi: 10.1161/CIRCULATIONAHA.111.032912. Epub 2012 Jan 18.
BACKGROUND
The clinical significance of the interaction between clopidogrel and proton pump inhibitors (PPIs) remains unclear.
METHODS AND RESULTS
We examined the relationship between PPI use and 1-year cardiovascular events (cardiovascular death, myocardial infarction, or stroke) in patients with acute coronary syndrome randomized to clopidogrel or ticagrelor in a prespecified, nonrandomized subgroup analysis of the Platelet Inhibition and Patient Outcomes (PLATO) trial. The primary end point rates were higher for individuals on a PPI (n=6539) compared with those not on a PPI (n=12 060) at randomization in both the clopidogrel (13.0% versus 10.9%; adjusted hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.04-1.38) and ticagrelor (11.0% versus 9.2%; HR, 1.24; 95% CI, 1.07-1.45) groups. Patients on non-PPI gastrointestinal drugs had similar primary end point rates compared with those on a PPI (PPI versus non-PPI gastrointestinal treatment: clopidogrel, HR, 0.98; 95% CI, 0.79-1.23; ticagrelor, HR, 0.89; 95% CI, 0.73-1.10). In contrast, patients on no gastric therapy had a significantly lower primary end point rate (PPI versus no gastrointestinal treatment: clopidogrel, HR, 1.29; 95% CI, 1.12-1.49; ticagrelor, HR, 1.30; 95% CI, 1.14-1.49).
CONCLUSIONS
The use of a PPI was independently associated with a higher rate of cardiovascular events in patients with acute coronary syndrome receiving clopidogrel. However, a similar association was observed between cardiovascular events and PPI use during ticagrelor treatment and with other non-PPI gastrointestinal treatment. Therefore, in the PLATO trial, the association between PPI use and adverse events may be due to confounding, with PPI use more of a marker for, than a cause of, higher rates of cardiovascular events.
CLINICAL TRIAL REGISTRATION
http://www.clinicaltrials.gov. Unique identifier: NCT00391872.
背景
氯吡格雷与质子泵抑制剂（PPIs）相互作用的临床意义尚不清楚。
方法和结果
我们在血小板抑制和患者结局（PLATO）试验的一个预先指定的非随机亚组分析中，检查了接受氯吡格雷或替格瑞洛治疗的急性冠脉综合征患者中 PPI 使用与 1 年心血管事件（心血管死亡、心肌梗死或卒中）之间的关系。在氯吡格雷（13.0%比 10.9%；调整后的危险比[HR]，1.20；95%置信区间[CI]，1.04-1.38）和替格瑞洛（11.0%比 9.2%；HR，1.24；95%CI，1.07-1.45）组中，随机分组时使用 PPI（n=6539）的个体比未使用 PPI（n=12060）的个体主要终点发生率更高。使用非 PPI 胃肠道药物的患者与使用 PPI 的患者主要终点发生率相似（PPI 与非 PPI 胃肠道治疗：氯吡格雷，HR，0.98；95%CI，0.79-1.23；替格瑞洛，HR，0.89；95%CI，0.73-1.10）。相比之下，未接受胃治疗的患者主要终点发生率显著降低（PPI 与无胃肠道治疗：氯吡格雷，HR，1.29；95%CI，1.12-1.49；替格瑞洛，HR，1.30；95%CI，1.14-1.49）。
结论
在接受氯吡格雷治疗的急性冠脉综合征患者中，使用 PPI 与心血管事件发生率升高独立相关。然而，在替格瑞洛治疗期间以及使用其他非 PPI 胃肠道治疗时，心血管事件与 PPI 使用之间也观察到类似的关联。因此，在 PLATO 试验中，PPI 使用与不良事件之间的关联可能是混杂因素所致，PPI 使用更多的是心血管事件发生率较高的标志物，而非原因。
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