Risk of Adverse Outcomes Associated With Concomitant Use of Clopidogrel and Proton Pump Inhibitors Following Acute Coronary Syndrome
Risk of Adverse Outcomes Associated With Concomitant Use of Clopidogrel and Proton Pump Inhibitors Following Acute Coronary Syndrome
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DOI：
10.1001/jama.2009.261
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发表时间：
2009-03-04
影响因子：
120.7
通讯作者：
Rumsfeld, John S.
中科院分区：
文献类型：
--
作者：
Ho, P. Michael;Maddox, Thomas M.;Rumsfeld, John S.
背景 先前的机制研究报道，奥美拉唑降低了氯吡格雷的血小板抑制作用，但这些发现的临床意义尚不清楚。 目的 评估因急性冠脉综合征 (ACS) 住院后服用氯吡格雷联合或不联合质子泵抑制剂 (PPI) 的患者的结局。 设计、环境和患者 10 月份期间从 127 家退伍军人事务医院出院后服用氯吡格雷的 8205 名 ACS 患者进行回顾性队列研究2003 年 1 月 1 日和 2006 年 1 月 31 日。截至 2006 年 9 月 30 日，所有患者的生命状况信息均可用。主要结果指标为全因死亡率或 ACS 的再住院。结果 在 8205 名出院后服用氯吡格雷的患者中，63.9%（n = 5244）在出院时、随访期间或两者均服用 PPI 36.1% (n = 2961) 没有服用 PPI。在不服用 PPI 的情况下服用氯吡格雷的患者中，有 20.8% (n = 615) 发生了 ACS 死亡或再住院的情况，而在服用氯吡格雷加 PPI 的患者中，这一比例为 29.8% (n = 1561)。在多变量分析中，与使用氯吡格雷而不加 PPI 相比，使用氯吡格雷加 PPI 与 ACS 死亡或再住院风险增加相关（调整后比值比 [AOR]，1.25；95% 置信区间 [CI]，1.11-1.41）。在出院后服用氯吡格雷并在随访期间的任何时间点开出 PPI 的患者 (n = 5244) 中，使用氯吡格雷加 PPI 的时间（与使用氯吡格雷而不使用 PPI 的时间相比）与较高的 ACS 死亡或再住院风险相关（调整后的风险比，1.27；95% CI，1.10-1.46）。在次要结局分析中，与服用氯吡格雷但不加 PPI 的患者相比，服用氯吡格雷加 PPI 的患者因复发 ACS 住院的风险更高（14.6% vs 6.9%；AOR，1.86 [ 95% CI，1.57-2.20]）和血运重建手术（15.5% vs 11.9%；AOR，1.49 [ 95% CI， 1.30-1.71]），但不适用于全因死亡率（19.9% vs 16.6%；AOR，0.91 [ 95% CI，0.80-1.05]）。使用氯吡格雷联合 PPI 与不良后果风险增加之间的关联也与巢式病例对照研究设计一致（AOR，1.32；95% CI，1.14-1.54）。此外，在出院后未服用氯吡格雷的患者中，不服用氯吡格雷而使用 PPI 与 ACS 死亡或再住院无关 (n = 6450)（AOR，0.98；95% CI，0.85-1.13）。 结论 因 ACS 出院后同时使用氯吡格雷和 PPI 与不使用氯吡格雷相比，不良后果风险增加相关。 PPI，表明 PPI 的使用可能与 ACS 后氯吡格雷的疗效减弱有关。
Context Prior mechanistic studies reported that omeprazole decreases the platelet inhibitory effects of clopidogrel, yet the clinical significance of these findings is not clear.Objective To assess outcomes of patients taking clopidogrel with or without a proton pump inhibitor (PPI) after hospitalization for acute coronary syndrome (ACS).Design, Setting, and Patients Retrospective cohort study of 8205 patients with ACS taking clopidogrel after discharge from 127 Veterans Affairs hospitals between October 1, 2003, and January 31, 2006. Vital status information was available for all patients through September 30, 2006.Main Outcome Measures All-cause mortality or rehospitalization for ACS.Results Of 8205 patients taking clopidogrel after discharge, 63.9% (n = 5244) were prescribed PPI at discharge, during follow-up, or both and 36.1% (n = 2961) were not prescribed PPI. Death or rehospitalization for ACS occurred in 20.8% (n = 615) of patients taking clopidogrel without PPI and 29.8% (n = 1561) of patients taking clopidogrel plus PPI. In multivariable analyses, use of clopidogrel plus PPI was associated with an increased risk of death or rehospitalization for ACS compared with use of clopidogrel without PPI ( adjusted odds ratio [AOR], 1.25; 95% confidence interval [CI], 1.11-1.41). Among patients taking clopidogrel after hospital discharge and prescribed PPI at any point during follow-up (n = 5244), periods of use of clopidogrel plus PPI ( compared with periods of use of clopidogrel without PPI) were associated with a higher risk of death or rehospitalization for ACS (adjusted hazard ratio, 1.27; 95% CI, 1.10-1.46). In analyses of secondary outcomes, patients taking clopidogrel plus PPI had a higher risk of hospitalizations for recurrent ACS compared with patients taking clopidogrel without PPI (14.6% vs 6.9%; AOR, 1.86 [ 95% CI, 1.57-2.20]) and revascularization procedures (15.5% vs 11.9%; AOR, 1.49 [ 95% CI, 1.30-1.71]), but not for all-cause mortality (19.9% vs 16.6%; AOR, 0.91 [ 95% CI, 0.80-1.05]). The association between use of clopidogrel plus PPI and increased risk of adverse outcomes also was consistent using a nested case-control study design (AOR, 1.32; 95% CI, 1.14-1.54). In addition, use of PPI without clopidogrel was not associated with death or rehospitalization for ACS among patients not taking clopidogrel after hospital discharge (n = 6450) ( AOR, 0.98; 95% CI, 0.85-1.13).Conclusion Concomitant use of clopidogrel and PPI after hospital discharge for ACS was associated with an increased risk of adverse outcomes than use of clopidogrel without PPI, suggesting that use of PPI may be associated with attenuation of benefits of clopidogrel after ACS.