Outcomes of a multi-ethnic Asian population on combined treatment with clopidogrel and omeprazole in 12,440 patients.

Abstract

Omeprazole is commonly co-prescribed with clopidogrel. Clopidogrel requires bio-activation by cytochrome P450 CYP2C19. Omeprazole may reduce clopidogrel's antithrombotic efficacy by inhibiting CYP2C19. Studies in Caucasians receiving omeprazole with clopidogrel showed no significant increase in death and myocardial infarction with this drug-drug interaction. There are limited large-scale studies in Asians, who may have a greater prevalence of CYP2C19 loss-of-function polymorphisms. A single centre retrospective cohort study was undertaken based on a review of medication records and prescription data. Patients prescribed clopidogrel from 2009 to 2012 were followed-up with until December 2012 (median:29 months). The primary outcome was all-cause mortality and secondary outcomes were myocardial infarction (MI), cerebrovascular accidents, and subsequent coronary interventions. Of 12,440 patients prescribed clopidogrel, 62%(n = 7714) were on omeprazole (63.8% Chinese, 13.9% Malay, 12.4% Indian, 10.0% others), and 38%(n = 4726) were not on omeprazole or other proton pump inhibitors (62.6% Chinese, 13.5% Malay, 10.7% Indian, 13.2% others). Mortality after co-prescription occurred in 14.3%(n = 1101) of patients, compared to 6.3%(n = 300) of patients prescribed clopidogrel only. Multivariate analysis using propensity score adjusted analysis showed no significant increase in all-cause mortality with co-prescription (adjusted hazards ratio [AHR] 1.13, [95%CI 0.95-1.35]). Patients on co-prescription had a higher risk of subsequent MI (16% vs 3.8%; AHR 2.03 [95%CI 1.70-2.44]), but not of cerebrovascular accidents (5.0% vs 2.0%; AHR 0.98 [95%CI 0.76-1.27]) or coronary interventions (1.7% vs 0.7%; AHR 1.28 [95%CI 0.83-1.96]). The risk of a subsequent MI was higher in the Malay (AHR 2.43 [95%CI 1.68-3.52]) and Chinese (AHR 2.06 [95%CI 1.63-2.60]) population as compared to the Indian (AHR 1.56 [95%CI 1.06-2.31]) population. In conclusion, the use of clopidogrel with omeprazole is associated with an increased risk of MI, but not mortality or stroke, in this multi-ethnic Asian population. These risks appear to vary among different ethnic groups.

• Authors: Mark D Muthiah, Huili Zheng, Nicholas W S Chew, Jieling Xiao, Lee Guan Lim, Huay-Cheem Tan, Chi-Hang Lee, Adrian F Low, Ling-Li Foo, A Mark Richards, Yock-Young Dan, K Y Ho, James W L Yip, Mark Y Chan
• Journal: Journal of thrombosis and thrombolysis (J Thromb Thrombolysis) Vol. 52 Issue 3 Pg. 925-933 (Oct 2021) ISSN: 1573-742X [Electronic] Netherlands
• PMID: 33959860 (Publication Type: Journal Article, Review)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Platelet Aggregation Inhibitors
• Proton Pump Inhibitors
• Clopidogrel
• Cytochrome P-450 CYP2C19
• Omeprazole
• Ticlopidine

Topics

• Asian People
• Clopidogrel (therapeutic use)
• Cytochrome P-450 CYP2C19
• Drug Interactions
• Ethnicity
• Humans
• Myocardial Infarction (drug therapy)
• Omeprazole (therapeutic use)
• Platelet Aggregation Inhibitors (therapeutic use)
• Proton Pump Inhibitors (therapeutic use)
• Retrospective Studies
• Stroke (drug therapy)
• Ticlopidine (therapeutic use)