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Comparative effectiveness and safety of proton pump inhibitors after myocardial infarction on dual antiplatelet therapy: Insights from a target trial emulation.

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Τίτλος: Comparative effectiveness and safety of proton pump inhibitors after myocardial infarction on dual antiplatelet therapy: Insights from a target trial emulation.
Συγγραφείς: Zhao L; Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China., Li L; Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China., Wu C; Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China., Liu H; Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China., Aa G; Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China., Chen X; Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China., Zhang Z; Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China., Chew NWS; Yong Loo-Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Department of Cardiology, National University Heart Centre, Singapore, Singapore., Chan MYY; Yong Loo-Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Department of Cardiology, National University Heart Centre, Singapore, Singapore.; Cardiovascular Research Institute, National University Health System, Singapore, Singapore., Sia CH; Yong Loo-Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Department of Cardiology, National University Heart Centre, Singapore, Singapore., Tan DS; Department of Pharmacy and Pharmaceutical Sciences, National University Singapore Faculty of Science, Singapore, Singapore., Sun P; Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China., Zhou X; Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China., Yang Q; Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China.
Πηγή: British journal of clinical pharmacology [Br J Clin Pharmacol] 2026 Oct; Vol. 92 (10), pp. 3466-3476. Date of Electronic Publication: 2026 Jun 17.
Τύπος έκδοσης: Journal Article; Comparative Study
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 7503323 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2125 (Electronic) Linking ISSN: 03065251 NLM ISO Abbreviation: Br J Clin Pharmacol Subsets: MEDLINE
Imprint Name(s): Publication: Oxford : Wiley-Blackwell
Original Publication: London, Macmillan Journals Ltd.
Ιατρικοί όροι (MeSH): Proton Pump Inhibitors*/adverse effects , Proton Pump Inhibitors*/administration & dosage , Proton Pump Inhibitors*/therapeutic use , Myocardial Infarction*/drug therapy , Gastrointestinal Hemorrhage*/chemically induced , Gastrointestinal Hemorrhage*/prevention & control , Gastrointestinal Hemorrhage*/epidemiology , Platelet Aggregation Inhibitors*/adverse effects , Platelet Aggregation Inhibitors*/administration & dosage , Dual Anti-Platelet Therapy*/adverse effects , Dual Anti-Platelet Therapy*/methods, Pantoprazole/adverse effects ; Pantoprazole/administration & dosage ; Rabeprazole/adverse effects ; Rabeprazole/administration & dosage ; Lansoprazole/adverse effects ; Lansoprazole/administration & dosage ; Humans ; Female ; Male ; Aged ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Proportional Hazards Models
Περίληψη: Background: Current guidelines recommend co-prescribing proton pump inhibitors (PPIs) with dual antiplatelet therapy (DAPT) after acute myocardial infarction (MI) to prevent gastrointestinal bleeding. Emerging evidence indicates that PPIs have distinct pharmacokinetic profiles, and their cardiovascular and bleeding effects may not represent a class effect.
Methods: We used electronic health record data from the Tianjin Health and Medical Data Platform to emulate target trials comparing effectiveness and safety of three commonly used PPIs in clinical practice. The effectiveness outcome was gastrointestinal bleeding, and the safety outcome was composite cardiovascular events. Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) between individual PPIs. We further applied XGBoost-based prognostic models to assess treatment effect heterogeneity across strata of predicted baseline risk.
Results: Of 51 072 MI patients on DAPT, 22 671 were prescribed rabeprazole, 18 081 pantoprazole and 10 320 lansoprazole. During 1 year of follow-up, both pantoprazole (HR, 1.05 [95% CI, 0.97-1.13]) and lansoprazole (HR, 0.99 [0.91-1.09]) showed comparable cardiovascular risk to rabeprazole, but pantoprazole was associated with an increased risk of recurrent MI (HR, 1.20 [1.07-1.35]). For gastrointestinal bleeding risk, lansoprazole showed lower risk (HR, 0.81 [0.70-0.93]) compared with rabeprazole. Results were robust in multiple sensitivity analyses, and treatment effect heterogeneity showed gastrointestinal benefits of lansoprazole increase with the rising baseline bleeding risk.
Conclusions: In patients with acute MI receiving DAPT, the three PPIs showed similar cardiovascular safety, while lansoprazole was associated with a lower risk of gastrointestinal bleeding. External validation is warranted to examine these findings.
(© 2026 British Pharmacological Society.)
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Grant Information: 2022YFF0706000 National Key Research and Development Program of China; 72274133 National Natural Science Foundation of China; 72304205 National Natural Science Foundation of China; 82270349 National Natural Science Foundation of China; 82320108001 National Natural Science Foundation of China; 82321001 National Natural Science Foundation of China; TJYXZDXK-069C Tianjin Key Medical Discipline (Specialty) Construction Project
Contributed Indexing: Keywords: bleeding prevention; cardiovascular outcome; myocardial infarction; proton pump inhibitors
Substance Nomenclature: 0 (Proton Pump Inhibitors)
0 (Platelet Aggregation Inhibitors)
D8TST4O562 (Pantoprazole)
32828355LL (Rabeprazole)
0K5C5T2QPG (Lansoprazole)
Entry Date(s): Date Created: 20260617 Date Completed: 20260928 Latest Revision: 20260928
Update Code: 20260929
DOI: 10.1002/bcp.70650
PMID: 42309503
Βάση Δεδομένων: MEDLINE
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  Data: Comparative effectiveness and safety of proton pump inhibitors after myocardial infarction on dual antiplatelet therapy: Insights from a target trial emulation.
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  Data: <searchLink fieldCode="AU" term="%22Zhao+L%22">Zhao L</searchLink>; Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China.<br /><searchLink fieldCode="AU" term="%22Li+L%22">Li L</searchLink>; Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China.<br /><searchLink fieldCode="AU" term="%22Wu+C%22">Wu C</searchLink>; Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China.<br /><searchLink fieldCode="AU" term="%22Liu+H%22">Liu H</searchLink>; Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China.<br /><searchLink fieldCode="AU" term="%22Aa+G%22">Aa G</searchLink>; Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China.<br /><searchLink fieldCode="AU" term="%22Chen+X%22">Chen X</searchLink>; Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China.<br /><searchLink fieldCode="AU" term="%22Zhang+Z%22">Zhang Z</searchLink>; Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China.<br /><searchLink fieldCode="AU" term="%22Chew+NWS%22">Chew NWS</searchLink>; Yong Loo-Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Department of Cardiology, National University Heart Centre, Singapore, Singapore.<br /><searchLink fieldCode="AU" term="%22Chan+MYY%22">Chan MYY</searchLink>; Yong Loo-Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Department of Cardiology, National University Heart Centre, Singapore, Singapore.; Cardiovascular Research Institute, National University Health System, Singapore, Singapore.<br /><searchLink fieldCode="AU" term="%22Sia+CH%22">Sia CH</searchLink>; Yong Loo-Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Department of Cardiology, National University Heart Centre, Singapore, Singapore.<br /><searchLink fieldCode="AU" term="%22Tan+DS%22">Tan DS</searchLink>; Department of Pharmacy and Pharmaceutical Sciences, National University Singapore Faculty of Science, Singapore, Singapore.<br /><searchLink fieldCode="AU" term="%22Sun+P%22">Sun P</searchLink>; Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China.<br /><searchLink fieldCode="AU" term="%22Zhou+X%22">Zhou X</searchLink>; Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China.<br /><searchLink fieldCode="AU" term="%22Yang+Q%22">Yang Q</searchLink>; Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China.
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  Data: <searchLink fieldCode="MM" term="%22Proton+Pump+Inhibitors%22">Proton Pump Inhibitors*</searchLink>/<searchLink fieldCode="MM" term="%22Proton+Pump+Inhibitors+adverse+effects%22">adverse effects</searchLink> <br /><searchLink fieldCode="MM" term="%22Proton+Pump+Inhibitors%22">Proton Pump Inhibitors*</searchLink>/<searchLink fieldCode="MM" term="%22Proton+Pump+Inhibitors+administration+%26+dosage%22">administration & dosage</searchLink> <br /><searchLink fieldCode="MM" term="%22Proton+Pump+Inhibitors%22">Proton Pump Inhibitors*</searchLink>/<searchLink fieldCode="MM" term="%22Proton+Pump+Inhibitors+therapeutic+use%22">therapeutic use</searchLink> <br /><searchLink fieldCode="MM" term="%22Myocardial+Infarction%22">Myocardial Infarction*</searchLink>/<searchLink fieldCode="MM" term="%22Myocardial+Infarction+drug+therapy%22">drug therapy</searchLink> <br /><searchLink fieldCode="MM" term="%22Gastrointestinal+Hemorrhage%22">Gastrointestinal Hemorrhage*</searchLink>/<searchLink fieldCode="MM" term="%22Gastrointestinal+Hemorrhage+chemically+induced%22">chemically induced</searchLink> <br /><searchLink fieldCode="MM" term="%22Gastrointestinal+Hemorrhage%22">Gastrointestinal Hemorrhage*</searchLink>/<searchLink fieldCode="MM" term="%22Gastrointestinal+Hemorrhage+prevention+%26+control%22">prevention & control</searchLink> <br /><searchLink fieldCode="MM" term="%22Gastrointestinal+Hemorrhage%22">Gastrointestinal Hemorrhage*</searchLink>/<searchLink fieldCode="MM" term="%22Gastrointestinal+Hemorrhage+epidemiology%22">epidemiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Platelet+Aggregation+Inhibitors%22">Platelet Aggregation Inhibitors*</searchLink>/<searchLink fieldCode="MM" term="%22Platelet+Aggregation+Inhibitors+adverse+effects%22">adverse effects</searchLink> <br /><searchLink fieldCode="MM" term="%22Platelet+Aggregation+Inhibitors%22">Platelet Aggregation Inhibitors*</searchLink>/<searchLink fieldCode="MM" term="%22Platelet+Aggregation+Inhibitors+administration+%26+dosage%22">administration & dosage</searchLink> <br /><searchLink fieldCode="MM" term="%22Dual+Anti-Platelet+Therapy%22">Dual Anti-Platelet Therapy*</searchLink>/<searchLink fieldCode="MM" term="%22Dual+Anti-Platelet+Therapy+adverse+effects%22">adverse effects</searchLink> <br /><searchLink fieldCode="MM" term="%22Dual+Anti-Platelet+Therapy%22">Dual Anti-Platelet Therapy*</searchLink>/<searchLink fieldCode="MM" term="%22Dual+Anti-Platelet+Therapy+methods%22">methods</searchLink><br /><searchLink fieldCode="MH" term="%22Pantoprazole%22">Pantoprazole</searchLink>/<searchLink fieldCode="MH" term="%22Pantoprazole+adverse+effects%22">adverse effects</searchLink> ; <searchLink fieldCode="MH" term="%22Pantoprazole%22">Pantoprazole</searchLink>/<searchLink fieldCode="MH" term="%22Pantoprazole+administration+%26+dosage%22">administration & dosage</searchLink> ; <searchLink fieldCode="MH" term="%22Rabeprazole%22">Rabeprazole</searchLink>/<searchLink fieldCode="MH" term="%22Rabeprazole+adverse+effects%22">adverse effects</searchLink> ; <searchLink fieldCode="MH" term="%22Rabeprazole%22">Rabeprazole</searchLink>/<searchLink fieldCode="MH" term="%22Rabeprazole+administration+%26+dosage%22">administration & dosage</searchLink> ; <searchLink fieldCode="MH" term="%22Lansoprazole%22">Lansoprazole</searchLink>/<searchLink fieldCode="MH" term="%22Lansoprazole+adverse+effects%22">adverse effects</searchLink> ; <searchLink fieldCode="MH" term="%22Lansoprazole%22">Lansoprazole</searchLink>/<searchLink fieldCode="MH" term="%22Lansoprazole+administration+%26+dosage%22">administration & dosage</searchLink> ; <searchLink fieldCode="MH" term="%22Humans%22">Humans</searchLink> ; <searchLink fieldCode="MH" term="%22Female%22">Female</searchLink> ; <searchLink fieldCode="MH" term="%22Male%22">Male</searchLink> ; <searchLink fieldCode="MH" term="%22Aged%22">Aged</searchLink> ; <searchLink fieldCode="MH" term="%22Middle+Aged%22">Middle Aged</searchLink> ; <searchLink fieldCode="MH" term="%22Treatment+Outcome%22">Treatment Outcome</searchLink> ; <searchLink fieldCode="MH" term="%22Drug+Therapy%2C+Combination%22">Drug Therapy, Combination</searchLink> ; <searchLink fieldCode="MH" term="%22Proportional+Hazards+Models%22">Proportional Hazards Models</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Background: Current guidelines recommend co-prescribing proton pump inhibitors (PPIs) with dual antiplatelet therapy (DAPT) after acute myocardial infarction (MI) to prevent gastrointestinal bleeding. Emerging evidence indicates that PPIs have distinct pharmacokinetic profiles, and their cardiovascular and bleeding effects may not represent a class effect.<br />Methods: We used electronic health record data from the Tianjin Health and Medical Data Platform to emulate target trials comparing effectiveness and safety of three commonly used PPIs in clinical practice. The effectiveness outcome was gastrointestinal bleeding, and the safety outcome was composite cardiovascular events. Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) between individual PPIs. We further applied XGBoost-based prognostic models to assess treatment effect heterogeneity across strata of predicted baseline risk.<br />Results: Of 51 072 MI patients on DAPT, 22 671 were prescribed rabeprazole, 18 081 pantoprazole and 10 320 lansoprazole. During 1 year of follow-up, both pantoprazole (HR, 1.05 [95% CI, 0.97-1.13]) and lansoprazole (HR, 0.99 [0.91-1.09]) showed comparable cardiovascular risk to rabeprazole, but pantoprazole was associated with an increased risk of recurrent MI (HR, 1.20 [1.07-1.35]). For gastrointestinal bleeding risk, lansoprazole showed lower risk (HR, 0.81 [0.70-0.93]) compared with rabeprazole. Results were robust in multiple sensitivity analyses, and treatment effect heterogeneity showed gastrointestinal benefits of lansoprazole increase with the rising baseline bleeding risk.<br />Conclusions: In patients with acute MI receiving DAPT, the three PPIs showed similar cardiovascular safety, while lansoprazole was associated with a lower risk of gastrointestinal bleeding. External validation is warranted to examine these findings.<br /> (© 2026 British Pharmacological Society.)
– Name: Ref
  Label: References
  Group: RefInfo
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– Name: GrantInfo
  Label: Grant Information
  Group: Grant
  Data: 2022YFF0706000 National Key Research and Development Program of China; 72274133 National Natural Science Foundation of China; 72304205 National Natural Science Foundation of China; 82270349 National Natural Science Foundation of China; 82320108001 National Natural Science Foundation of China; 82321001 National Natural Science Foundation of China; TJYXZDXK-069C Tianjin Key Medical Discipline (Specialty) Construction Project
– Name: SubjectMinor
  Label: Contributed Indexing
  Group:
  Data: <i>Keywords: </i>bleeding prevention; cardiovascular outcome; myocardial infarction; proton pump inhibitors
– Name: NumberCAS
  Label: Substance Nomenclature
  Group: ID
  Data: 0 (Proton Pump Inhibitors)<br />0 (Platelet Aggregation Inhibitors)<br />D8TST4O562 (Pantoprazole)<br />32828355LL (Rabeprazole)<br />0K5C5T2QPG (Lansoprazole)
– Name: DateEntry
  Label: Entry Date(s)
  Group: Date
  Data: <i>Date Created: </i>20260617 <i>Date Completed: </i>20260928 <i>Latest Revision: </i>20260928
– Name: DateUpdate
  Label: Update Code
  Group: Date
  Data: 20260929
– Name: DOI
  Label: DOI
  Group: ID
  Data: 10.1002/bcp.70650
– Name: AN
  Label: PMID
  Group: ID
  Data: 42309503
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cmedm&AN=42309503
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    Identifiers:
      – Type: doi
        Value: 10.1002/bcp.70650
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      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        StartPage: 3466
    Subjects:
      – SubjectFull: Pantoprazole adverse effects
        Type: general
      – SubjectFull: Pantoprazole administration & dosage
        Type: general
      – SubjectFull: Rabeprazole adverse effects
        Type: general
      – SubjectFull: Rabeprazole administration & dosage
        Type: general
      – SubjectFull: Lansoprazole adverse effects
        Type: general
      – SubjectFull: Lansoprazole administration & dosage
        Type: general
      – SubjectFull: Humans
        Type: general
      – SubjectFull: Female
        Type: general
      – SubjectFull: Male
        Type: general
      – SubjectFull: Aged
        Type: general
      – SubjectFull: Middle Aged
        Type: general
      – SubjectFull: Treatment Outcome
        Type: general
      – SubjectFull: Drug Therapy, Combination
        Type: general
      – SubjectFull: Proportional Hazards Models
        Type: general
      – SubjectFull: Proton Pump Inhibitors adverse effects
        Type: general
      – SubjectFull: Proton Pump Inhibitors administration & dosage
        Type: general
      – SubjectFull: Proton Pump Inhibitors therapeutic use
        Type: general
      – SubjectFull: Myocardial Infarction drug therapy
        Type: general
      – SubjectFull: Gastrointestinal Hemorrhage chemically induced
        Type: general
      – SubjectFull: Gastrointestinal Hemorrhage prevention & control
        Type: general
      – SubjectFull: Gastrointestinal Hemorrhage epidemiology
        Type: general
      – SubjectFull: Platelet Aggregation Inhibitors adverse effects
        Type: general
      – SubjectFull: Platelet Aggregation Inhibitors administration & dosage
        Type: general
      – SubjectFull: Dual Anti-Platelet Therapy adverse effects
        Type: general
      – SubjectFull: Dual Anti-Platelet Therapy methods
        Type: general
    Titles:
      – TitleFull: Comparative effectiveness and safety of proton pump inhibitors after myocardial infarction on dual antiplatelet therapy: Insights from a target trial emulation.
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            – D: 01
              M: 10
              Text: 2026 Oct
              Type: published
              Y: 2026
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            – TitleFull: British journal of clinical pharmacology
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