Evidence map›Paper›PMID 41783931›Full record

Observational studyArteriosclerosis, thrombosis, and vascular biology2026

Comparison of Cardiovascular Events in Patients Receiving Concomitant Clopidogrel and Proton Pump Inhibitors Classified by CYP2C19 Inhibitory Potency.

Seonji Kim, Jimyung Park, Hsin Yi Chen, Christianus Heru Setiawan, Haeun Lee, Benjamin Martin, Kyung Joo Lee, George Hripcsak, Jason C Hsu, Paul Nagy and 8 more

Abstract readComparative StudyObservational StudyMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Arteriosclerosis, thrombosis, and vascular biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Seonji KimDepartment of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Korea (Seonji Kim, Subin Kim, S.C.Y.).ORCID 0000-0002-4993-7537
Jimyung ParkDivision of Hematology/Oncology, Department of Medicine, (J.P.), Columbia University Irving Medical Center, New York, NY.ORCID 0000-0002-6998-2546
Hsin Yi ChenDepartment of Biomedical Informatics (H.Y.C., G.H.), Columbia University Irving Medical Center, New York, NY.ORCID 0000-0002-7907-2335
Christianus Heru SetiawanSchool of Pharmacy (C.H.S.), Taipei Medical University, Taiwan.
Haeun LeeBiomedical Informatics and Data Science, Johns Hopkins University, Baltimore, MD (H.L., B.M., P.N.).ORCID 0000-0002-9597-9447
Benjamin MartinBiomedical Informatics and Data Science, Johns Hopkins University, Baltimore, MD (H.L., B.M., P.N.).ORCID 0000-0001-6510-6824
Kyung Joo LeeDepartment of Medical Informatics and Statistics (K.J.L.), Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea.ORCID 0000-0002-5965-8064
George HripcsakDepartment of Biomedical Informatics (H.Y.C., G.H.), Columbia University Irving Medical Center, New York, NY.ORCID 0000-0003-2664-7614
Jason C HsuInternational Ph.D. Program in Biotech and Healthcare Management, College of Management (J.C.H., P.T.-P., M.S.M.), Taipei Medical University, Taiwan.ORCID 0000-0003-2997-2404
Paul NagyBiomedical Informatics and Data Science, Johns Hopkins University, Baltimore, MD (H.L., B.M., P.N.).ORCID 0000-0001-5108-7749
Subin KimDepartment of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Korea (Seonji Kim, Subin Kim, S.C.Y.).ORCID 0000-0001-7155-2273
Phung-Anh NguyenClinical Big Data Research Center, Taipei Medical University Hospital (J.C.H., P.-A.N.), Taipei Medical University, Taiwan.
Phan Thanh-PhucInternational Ph.D. Program in Biotech and Healthcare Management, College of Management (J.C.H., P.T.-P., M.S.M.), Taipei Medical University, Taiwan.
Muhammad Solihuddin MuhtarInternational Ph.D. Program in Biotech and Healthcare Management, College of Management (J.C.H., P.T.-P., M.S.M.), Taipei Medical University, Taiwan.
Min-Huei HsuGraduate Institute of Data Science, College of Management (M.-H.H.), Taipei Medical University, Taiwan.ORCID 0000-0003-3607-2463
Woon Geon ShinDepartment of Internal Medicine (W.G.S., S.I.S.), Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea.ORCID 0000-0002-9851-5576
Seng Chan You *Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Korea (Seonji Kim, Subin Kim, S.C.Y.).ORCID 0000-0002-5052-6399
Seung In Seo *Department of Internal Medicine (W.G.S., S.I.S.), Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea.ORCID 0000-0003-4417-0135

Funding

Training in Biomedical Informatics at Columbia UniversityT15LM007079 · NLM · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI NOEMIE ELHADAD, GEORGE M HRIPCSAK · 1992 to 2026
$28.9M
DISCOVERING AND APPLYING KNOWLEDGE IN CLINICAL DATABASESR01LM006910 · NLM · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI HRIPCSAK, GEORGE M · 2000 to 2023
$10.6M
NLM NIH HHS R01 LM006910NLM NIH HHS T15 LM007079
6 · The paper itself

Abstract

backgroundProton pump inhibitors (PPIs) may potentially reduce clopidogrel's antiplatelet effect and increase cardiovascular risk. The degree of CYP (cytochrome P450) 2C19 inhibition varies among PPIs. Few studies have evaluated individual PPIs by CYP2C19 inhibition strength across countries. This study aimed to compare the incidence of cardiovascular events between strong CYP2C19-inhibiting potency and weak CYP2C19-inhibiting potency (weak or non-CYP2C19-inhibiting PPIs) in patients receiving clopidogrel.

methodsWe conducted an international observational cohort study using 14 databases from the United States, South Korea, and Taiwan. We included patients aged ≥18 years who received clopidogrel with PPIs from 1985 to 2023. PPIs were classified into strong CYP2C19-inhibiting PPIs and weak or non-CYP2C19-inhibiting PPIs based on CYP2C19 inhibition. We compared the hazard ratios and 95% CIs for major adverse cardiovascular events, including myocardial infarction, stroke, and cardiovascular mortality, using the Cox proportional hazards model after 1:1 propensity score matching. Secondary outcomes included cardiovascular mortality, myocardial infarction, stroke, and all-cause mortality. A random-effects model calculated pooled hazard ratios and 95% CIs. Only databases meeting all diagnostic criteria were included in the meta-analysis.

resultsLarge-scale propensity score matching identified 166 005 patient pairs. During the 365-day follow-up, the risk of major adverse cardiovascular events did not differ significantly between patients receiving clopidogrel plus strong CYP2C19-inhibiting PPIs and those receiving clopidogrel plus weak or non-CYP2C19-inhibiting PPIs (17.63 per 1000 person-years versus 16.82 per 1000 person-years; calibrated hazard ratio, 1.00 [95% CI, 0.79-1.26]). No significant difference was observed in the risk of secondary outcomes (calibrated hazard ratio, cardiovascular mortality 1.10 [95% CI, 0.87-1.39], myocardial infarction 0.98 [95% CI, 0.81-1.19], stroke 1.05 [95% CI, 0.87-1.27], and all-cause mortality 1.18 [95% CI, 0.93-1.50]).

conclusionsConcomitant use of clopidogrel and strong CYP2C19-inhibiting PPIs was not associated with a higher cardiovascular risk compared with concomitant use of clopidogrel and weak or non-CYP2C19-inhibiting PPIs. This large-scale study does not support the clinical significance of potential interactions between PPIs and clopidogrel.

Indexed as

Cardiovascular DiseasesClopidogrelCytochrome P-450 CYP2C19Cytochrome P-450 CYP2C19 InhibitorsPlatelet Aggregation InhibitorsProton Pump InhibitorsAgedDatabases, FactualDrug InteractionsDrug Therapy, CombinationFemaleHumansMaleMiddle AgedRepublic of KoreaRisk AssessmentClopidogrelCYP2C19 protein, humanCytochrome P-450 CYP2C19Cytochrome P-450 CYP2C19 InhibitorsPlatelet Aggregation InhibitorsProton Pump Inhibitorscardiovascular diseasesclopidogrelmortalitymyocardial infarctionproton pump inhibitorsstroke

Identifiers

PMID41783931
PMCPMC13140470

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.