Evidence map›Paper›PMID 25657176›Full record

ArticleStroke2015

Comparative risk of ischemic stroke among users of clopidogrel together with individual proton pump inhibitors.

Charles E Leonard, Warren B Bilker, Colleen M Brensinger, David A Flockhart, Cristin P Freeman, Scott E Kasner, Stephen E Kimmel, Sean Hennessy

Open access · bronzeAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Stroke, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 2 pooled it
3.4field-weighted citation impact, top 7% of its field
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

16 citing papers in PubMed, 2 syntheses or guidelines pooled it, 31 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Concomitant Use of Proton-Pump Inhibitors and Clopidogrel Increases the Risk of Adverse Outcomes in Patients With Ischemic Stroke Carrying Reduced-Function CYP2C19*2.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis · 2018
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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

8 authors at 2 institutions in 1 country.

Charles E LeonardFrom the Center for Clinical Epidemiology and Biostatistics (C.E.L., W.B.B., C.M.B., C.P.F., S.E. Kimmel, S.H.), Center for Pharmacoepidemiology Research and Training (C.E.L., W.B.B., D.A.F., C.P.F., S.E. Kimmel, S.H.), Department of Psychiatry (W.B.B.), Department of Neurology (S.E. Kasner), Division of Cardiovascular Medicine, Department of Medicine (S.E. Kimmel), and Department of Systems Pharmacology and Translational Therapeutics (S.H.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; and Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis (D.A.F.). celeonar@mail.med.upenn.edu.
Warren B BilkerFrom the Center for Clinical Epidemiology and Biostatistics (C.E.L., W.B.B., C.M.B., C.P.F., S.E. Kimmel, S.H.), Center for Pharmacoepidemiology Research and Training (C.E.L., W.B.B., D.A.F., C.P.F., S.E. Kimmel, S.H.), Department of Psychiatry (W.B.B.), Department of Neurology (S.E. Kasner), Division of Cardiovascular Medicine, Department of Medicine (S.E. Kimmel), and Department of Systems Pharmacology and Translational Therapeutics (S.H.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; and Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis (D.A.F.).
Colleen M BrensingerFrom the Center for Clinical Epidemiology and Biostatistics (C.E.L., W.B.B., C.M.B., C.P.F., S.E. Kimmel, S.H.), Center for Pharmacoepidemiology Research and Training (C.E.L., W.B.B., D.A.F., C.P.F., S.E. Kimmel, S.H.), Department of Psychiatry (W.B.B.), Department of Neurology (S.E. Kasner), Division of Cardiovascular Medicine, Department of Medicine (S.E. Kimmel), and Department of Systems Pharmacology and Translational Therapeutics (S.H.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; and Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis (D.A.F.).
David A FlockhartFrom the Center for Clinical Epidemiology and Biostatistics (C.E.L., W.B.B., C.M.B., C.P.F., S.E. Kimmel, S.H.), Center for Pharmacoepidemiology Research and Training (C.E.L., W.B.B., D.A.F., C.P.F., S.E. Kimmel, S.H.), Department of Psychiatry (W.B.B.), Department of Neurology (S.E. Kasner), Division of Cardiovascular Medicine, Department of Medicine (S.E. Kimmel), and Department of Systems Pharmacology and Translational Therapeutics (S.H.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; and Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis (D.A.F.).
Cristin P FreemanFrom the Center for Clinical Epidemiology and Biostatistics (C.E.L., W.B.B., C.M.B., C.P.F., S.E. Kimmel, S.H.), Center for Pharmacoepidemiology Research and Training (C.E.L., W.B.B., D.A.F., C.P.F., S.E. Kimmel, S.H.), Department of Psychiatry (W.B.B.), Department of Neurology (S.E. Kasner), Division of Cardiovascular Medicine, Department of Medicine (S.E. Kimmel), and Department of Systems Pharmacology and Translational Therapeutics (S.H.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; and Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis (D.A.F.).
Scott E KasnerFrom the Center for Clinical Epidemiology and Biostatistics (C.E.L., W.B.B., C.M.B., C.P.F., S.E. Kimmel, S.H.), Center for Pharmacoepidemiology Research and Training (C.E.L., W.B.B., D.A.F., C.P.F., S.E. Kimmel, S.H.), Department of Psychiatry (W.B.B.), Department of Neurology (S.E. Kasner), Division of Cardiovascular Medicine, Department of Medicine (S.E. Kimmel), and Department of Systems Pharmacology and Translational Therapeutics (S.H.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; and Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis (D.A.F.).
Stephen E KimmelFrom the Center for Clinical Epidemiology and Biostatistics (C.E.L., W.B.B., C.M.B., C.P.F., S.E. Kimmel, S.H.), Center for Pharmacoepidemiology Research and Training (C.E.L., W.B.B., D.A.F., C.P.F., S.E. Kimmel, S.H.), Department of Psychiatry (W.B.B.), Department of Neurology (S.E. Kasner), Division of Cardiovascular Medicine, Department of Medicine (S.E. Kimmel), and Department of Systems Pharmacology and Translational Therapeutics (S.H.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; and Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis (D.A.F.).
Sean HennessyFrom the Center for Clinical Epidemiology and Biostatistics (C.E.L., W.B.B., C.M.B., C.P.F., S.E. Kimmel, S.H.), Center for Pharmacoepidemiology Research and Training (C.E.L., W.B.B., D.A.F., C.P.F., S.E. Kimmel, S.H.), Department of Psychiatry (W.B.B.), Department of Neurology (S.E. Kasner), Division of Cardiovascular Medicine, Department of Medicine (S.E. Kimmel), and Department of Systems Pharmacology and Translational Therapeutics (S.H.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; and Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis (D.A.F.).
Translational Therapeutics (United States) · USUniversity of Pennsylvania · US

Funding

Institutional Clinical and Translational Science AwardUL1TR000003 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI FITZGERALD, GARRET A · 2012 to 2015
$38.9M
Clinical Importance of Drug-Drug InteractionsR01AG025152 · NIA · UNIVERSITY OF PENNSYLVANIA · PI HENNESSY, SEAN, LI, LANG · 2006 to 2021
$8.1M
Drug-Drug Interactions Involving Antidiabetic AgentsR01DK102694 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI HENNESSY, SEAN, LI, LANG · 2014 to 2017
$2.4M
NCATS NIH HHS UL1 TR000003NCATS NIH HHS UL1TR000003NIA NIH HHS R01 AG025152NIA NIH HHS R01AG025152NIDDK NIH HHS R01 DK102694NIDDK NIH HHS R01DK102694
6 · The paper itself

Abstract

background and purposeThere is controversy and little information about whether individual proton pump inhibitors (PPIs) differentially alter the effectiveness of clopidogrel in reducing ischemic stroke risk. We, therefore, aimed to elucidate the risk of ischemic stroke among concomitant users of clopidogrel and individual PPIs.

methodsWe conducted a propensity score-adjusted cohort study of adult new users of clopidogrel, using 1999 to 2009 Medicaid claims from 5 large states. Exposures were defined by prescriptions for esomeprazole, lansoprazole, omeprazole, rabeprazole, and pantoprazole-with pantoprazole serving as the referent. The end point was hospitalization for acute ischemic stroke, defined by International Classification of Diseases Ninth Revision Clinical Modification codes in the principal position on inpatient claims, within 180 days of concomitant therapy initiation.

resultsAmong 325 559 concomitant users of clopidogrel and a PPI, we identified 1667 ischemic strokes for an annual incidence of 2.4% (95% confidence interval, 2.3-2.5). Adjusted hazard ratios for ischemic stroke versus pantoprazole were 0.98 (0.82-1.17) for esomeprazole; 1.06 (0.92-1.21) for lansoprazole; 0.98 (0.85-1.15) for omeprazole; and 0.85 (0.63-1.13) for rabeprazole.

conclusionsPPIs of interest did not increase the rate of ischemic stroke among clopidogrel users when compared with pantoprazole, a PPI thought to be devoid of the potential to interact with clopidogrel.

Indexed as

2-PyridinylmethylsulfinylbenzimidazolesAgedAged, 80 and overBrain IschemiaClopidogrelData Interpretation, StatisticalDrug Therapy, CombinationEsomeprazoleFemaleHumansLansoprazoleMaleMiddle AgedOmeprazolePantoprazoleProportional Hazards Models2-PyridinylmethylsulfinylbenzimidazolesClopidogrelEsomeprazoleLansoprazoleOmeprazolePantoprazoleProton Pump InhibitorsRabeprazoleTiclopidinecohort studiesdrug interactionsMedicaidpharmacoepidemiologyplatelet aggregation inhibitorsproton pump inhibitorsstroke

Identifiers

PMID25657176
PMCPMC4342326
OpenAlexW1988733658

What OpenQuestion holds

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Registered trials

None linked

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.