Guérin Annie, Mody Reema, Carter Valerie, Ayas Charles, Patel Haridarshan, Lasch Karen, Wu Eric
Analysis Group, Inc., Montreal, Quebec, Canada.
Takeda Pharmaceuticals International, Inc., Health Economics and Outcomes Research, Deerfield, Illinois, United States of America.
PLoS One. 2016 Jan 4;11(1):e0145504. doi: 10.1371/journal.pone.0145504. eCollection 2016.
In 2009, the FDA issued a warning that omeprazole--a proton pump inhibitor (PPI)--reduces the antithrombotic effect of clopidogrel by almost half when taken concomitantly. This study aims to analyze the impact of the FDA Safety Communications on prescribing clopidogrel together with PPIs.
This retrospective study identified clopidogrel users from the Truven Health Analytics MarketScan Databases (01/2006-12/2012). Rates of clopidogrel-PPI combination therapy were estimated in 6-month intervals for patients with ≥1 clopidogrel prescription fill, then were analyzed pre- and post-safety communication (11/17/2009). Analyses were also conducted by grouping PPIs into CYP2C19 inhibitors (omeprazole and esomeprazole) and CYP2C19 non-inhibitors (pantoprazole, lansoprazole, dexlansoprazole, and rabeprazole).
Overall, 483,074 patients met the selection criteria; of these, 157,248 used a clopidogrel-PPI combination. On average, 30.5% of patients in the pre- and 19.9% in the post-communication period used a clopidogrel-PPI combination therapy. Among clopidogrel users, the probability of using clopidogrel-PPI combinations fell by over 40% in the post-communication period (OR = 0.57; p<0.001); the proportion of patients using esomeprazole fell from 12.9% to 5.3%, and the proportion using omeprazole fell from 10.1% to 6.3%. Among combination therapy users, the probability of patients using a combination with a CYP2C19 inhibitor decreased by 53% (OR = 0.47; p<0.001); however, 31.5% of patients were still prescribed a clopidogrel-PPI combination therapy. Trends were similar for all and newly treated patients, regardless of clopidogrel indication and physician specialty.
The FDA Safety Communication resulted in a reduction in the number of patients undergoing combination therapy; however approximately one-third of patients still used combination therapy post-communication.
2009年，美国食品药品监督管理局（FDA）发布一项警告，质子泵抑制剂（PPI）奥美拉唑与氯吡格雷同时服用时，会使氯吡格雷的抗血栓作用降低近一半。本研究旨在分析FDA安全通讯对氯吡格雷与PPI联合处方的影响。
这项回顾性研究从Truven Health Analytics MarketScan数据库（2006年1月至2012年12月）中确定氯吡格雷使用者。对至少有1次氯吡格雷处方配药的患者，按6个月间隔估算氯吡格雷 - PPI联合治疗的比例，然后分析安全通讯发布前后（2009年11月17日）的情况。还通过将PPI分为CYP2C19抑制剂（奥美拉唑和埃索美拉唑）和CYP2C19非抑制剂（泮托拉唑、兰索拉唑、右兰索拉唑和雷贝拉唑）进行分析。
总体而言，483,074名患者符合入选标准；其中，157,248名使用了氯吡格雷 - PPI联合治疗。在通讯发布前，平均有30.5%的患者使用氯吡格雷 - PPI联合治疗，通讯发布后这一比例为19.9%。在氯吡格雷使用者中，通讯发布后使用氯吡格雷 - PPI联合治疗的概率下降了40%以上（比值比[OR]=0.57；p<0.001）；使用埃索美拉唑的患者比例从12.9%降至5.3%，使用奥美拉唑的患者比例从10.1%降至6.3%。在联合治疗使用者中，使用CYP2C19抑制剂联合治疗的患者概率下降了53%（OR = 0.47；p<0.001）；然而，仍有31.5%的患者被处方氯吡格雷 - PPI联合治疗。所有患者和新治疗患者的趋势相似，无论氯吡格雷的适应证和医生专业如何。
FDA安全通讯导致联合治疗的患者数量减少；然而通讯发布后仍有大约三分之一的患者使用联合治疗。
