Proton pump inhibitor: Difference between revisions

From Citizendium
Jump to navigation Jump to search
imported>Robert Badgett
imported>Robert Badgett
Line 34: Line 34:
In the [[United States]], the [[Food and Drug Administration]] has issued warnings regarding combining PPIs with [[clopidogrel]].<ref>Anonymous. (2009) [http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm079520.htm Early Communication about an Ongoing Safety Review of clopidogrel bisulfate (marketed as Plavix)]</ref><ref>Anonymous (11/17/2009) [http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm190787.htm Information for Healthcare Professionals: Update to the labeling of Clopidogrel Bisulfate (marketed as Plavix) to alert healthcare professionals about a drug interaction with omeprazole (marketed as Prilosec and Prilosec OTC)]</ref>
In the [[United States]], the [[Food and Drug Administration]] has issued warnings regarding combining PPIs with [[clopidogrel]].<ref>Anonymous. (2009) [http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm079520.htm Early Communication about an Ongoing Safety Review of clopidogrel bisulfate (marketed as Plavix)]</ref><ref>Anonymous (11/17/2009) [http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm190787.htm Information for Healthcare Professionals: Update to the labeling of Clopidogrel Bisulfate (marketed as Plavix) to alert healthcare professionals about a drug interaction with omeprazole (marketed as Prilosec and Prilosec OTC)]</ref>
{| class="wikitable"
{| class="wikitable"
|+ Studies of [[drug interaction]]s between PPIs and [[clopidogrel]]<ref name="pmid19176635">{{cite journal| author=Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC, Tu JV et al.| title=A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. | journal=CMAJ | year= 2009 | volume= 180 | issue= 7 | pages= 713-8 | pmid=19176635  
|+ Studies of [[drug interaction]]s between PPIs and [[clopidogrel]]<ref name="pmid20231564">{{cite journal| author=Ray WA, Murray KT, Griffin MR, Chung CP, Smalley WE, Hall K et al.| title=Outcomes with concurrent use of clopidogrel and proton-pump inhibitors: a cohort study. | journal=Ann Intern Med | year= 2010 | volume= 152 | issue= 6 | pages= 337-45 | pmid=20231564
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19176635 | doi=10.1503/cmaj.082001 | pmc=PMC2659819 }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19687487 Review in: Ann Intern Med. 2009 Aug 18;151(4):JC2-13]  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19794029 Review in: Evid Based Med. 2009 Oct;14(5):154] <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref><ref name="pmid19258584">{{cite journal |author=Ho PM, Maddox TM, Wang L, ''et al.'' |title=Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome |journal=JAMA |volume=301 |issue=9 |pages=937–44 |year=2009 |month=March |pmid=19258584 |doi=10.1001/jama.2009.261 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=19258584 |issn=}}</ref><ref name="pmid19726078">{{cite journal| author=O'Donoghue ML, Braunwald E, Antman EM, Murphy SA, Bates ER, Rozenman Y et al.| title=Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials. | journal=Lancet | year= 2009 | volume= 374 | issue= 9694 | pages= 989-97 | pmid=19726078  
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=20231564 | doi=10.1059/0003-4819-152-6-201003160-00003 }} </ref><ref name="pmid19176635">{{cite journal| author=Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC, Tu JV et al.| title=A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. | journal=CMAJ | year= 2009 | volume= 180 | issue= 7 | pages= 713-8 | pmid=19176635  
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19726078 | doi=10.1016/S0140-6736(09)61525-7 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref><ref name="medco">Stanek EJ et al. (2009) [http://www.scai.org/annualmeeting/ A National Study of the Effect of Individual Proton Pump Inhibitors on Cardiovascular Outcomes in Patients Treated with Clopidogrel Following Coronary Stenting: The Clopidogrel Medco Outcomes Study] Society for Cardiovascular Angiography and Interventions 2009 Annual Meeting</ref>
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19176635 | doi=10.1503/cmaj.082001 | pmc=PMC2659819 }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19687487 Review in: Ann Intern Med. 2009 Aug 18;151(4):JC2-13]  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19794029 Review in: Evid Based Med. 2009 Oct;14(5):154]</ref><ref name="pmid19258584">{{cite journal |author=Ho PM, Maddox TM, Wang L, ''et al.'' |title=Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome |journal=JAMA |volume=301 |issue=9 |pages=937–44 |year=2009 |month=March |pmid=19258584 |doi=10.1001/jama.2009.261 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=19258584 |issn=}}</ref><ref name="pmid19726078">{{cite journal| author=O'Donoghue ML, Braunwald E, Antman EM, Murphy SA, Bates ER, Rozenman Y et al.| title=Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials. | journal=Lancet | year= 2009 | volume= 374 | issue= 9694 | pages= 989-97 | pmid=19726078  
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19726078 | doi=10.1016/S0140-6736(09)61525-7 }}</ref><ref name="medco">Stanek EJ et al. (2009) [http://www.scai.org/annualmeeting/ A National Study of the Effect of Individual Proton Pump Inhibitors on Cardiovascular Outcomes in Patients Treated with Clopidogrel Following Coronary Stenting: The Clopidogrel Medco Outcomes Study] Society for Cardiovascular Angiography and Interventions 2009 Annual Meeting</ref>
! rowspan="2"|Trial!!rowspan="2"| Patients!!rowspan="2"| Intervention!!rowspan="2"|Comparison !!rowspan="2"|Outcome!!colspan="2"|Results
! rowspan="2"|Trial!!rowspan="2"| Patients!!rowspan="2"| Intervention!!rowspan="2"|Comparison !!rowspan="2"|Outcome!!colspan="2"|Results
|-<br/>
|-<br/>
! PPI!!Control
! PPI!!Control
|-
|rowspan="2"|Tennessee Medicaid [[cohort study]]<ref name="pmid20231564"/>||rowspan="2"|20,596 patients hospitalized for [[myocardial infarction]], [[myocardial revascularization]], or unstable angina pectoris||rowspan="2"|7593 concurrent users of clopidogrel and PPIs<br/>&bull;&nbsp;62% used [[pantoprazole]]||rowspan="2"|13003 patients not taking PPIs||rowspan="2"|Serious cardiovascular disease||
|-
| colspan="2"|"Serious cardiovascular disease was not increased; however, the 95% CI  included a clinically important increased risk"
|-
|-
| Ontario nested [[case-control study]]<ref name="pmid19176635"/> || 13,636 subjects taking [[clopidogrel]] after [[myocardial infarction]]||782 subjects readmitted for [[myocardial infarction]]||2057 subjects not readmitted||Rate of PPI usage other than [[pantoprazole]]|| colspan="2"| [[Odds ratio]] = 1.40 (95% CI 1.10–1.77)
| Ontario nested [[case-control study]]<ref name="pmid19176635"/> || 13,636 subjects taking [[clopidogrel]] after [[myocardial infarction]]||782 subjects readmitted for [[myocardial infarction]]||2057 subjects not readmitted||Rate of PPI usage other than [[pantoprazole]]|| colspan="2"| [[Odds ratio]] = 1.40 (95% CI 1.10–1.77)
|-
|-
| rowspan="2"|[[Cohort study]] from the [[United States Veterans Health Administration|VA]] Cardiac Care Follow-up Clinical Study<ref name="pmid19258584"/> ||rowspan="2"| 8205 subjects with [[acute coronary syndrome]]||rowspan="2"| 64% were taking PPIs:<br/>&bull; 0.2% used [[pantoprazole]]<br/>&bull; 50% received [[stent]]s<br/>&bull; Probably < 50% used drug eluting [[stent]]s<ref name="pmid17967588">{{cite journal| author=Ho PM, Fihn SD, Wang L, Bryson CL, Lowy E, Maynard C et al.| title=Clopidogrel and long-term outcomes after stent implantation for acute coronary syndrome. | journal=Am Heart J | year= 2007 | volume= 154 | issue= 5 | pages= 846-51 | pmid=17967588  
| rowspan="2"|[[Cohort study]] from the [[United States Veterans Health Administration|VA]] Cardiac Care Follow-up Clinical Study<ref name="pmid19258584"/> ||rowspan="2"| 8205 subjects with [[acute coronary syndrome]]||rowspan="2"| 64% were taking PPIs:<br/>&bull; 0.2% used [[pantoprazole]]<br/>&bull; 50% received [[stent]]s<br/>&bull; Probably < 50% used drug eluting [[stent]]s<ref name="pmid17967588">{{cite journal| author=Ho PM, Fihn SD, Wang L, Bryson CL, Lowy E, Maynard C et al.| title=Clopidogrel and long-term outcomes after stent implantation for acute coronary syndrome. | journal=Am Heart J | year= 2007 | volume= 154 | issue= 5 | pages= 846-51 | pmid=17967588  
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17967588 | doi=10.1016/j.ahj.2007.08.028 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref><!-- in a secondary analysis: <br/>&bull; Excluded patients with [[Gastrointestinal hemorrhage|GI bleeding]]s<br/>&bull; Excluded patients taking [[Histamine H2 antagonist|H<sub>2</sub> blocker]]s-->||rowspan="2"|Subjects not taking PPIs||rowspan="2"| Major vascular events|| 29.8%|| 20.8%
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17967588 | doi=10.1016/j.ahj.2007.08.028 }}</ref><!-- in a secondary analysis: <br/>&bull; Excluded patients with [[Gastrointestinal hemorrhage|GI bleeding]]s<br/>&bull; Excluded patients taking [[Histamine H2 antagonist|H<sub>2</sub> blocker]]s-->||rowspan="2"|Subjects not taking PPIs||rowspan="2"| Major vascular events|| 29.8%|| 20.8%
|-
|-
| colspan="2"|[[Odds ratio]] = 1.25 (95% CI: 1.11-1.41)<br/>&bull; "each 10% increase in the proportion of time taking clopidogrel plus PPI during follow-up was associated with a higher risk"
| colspan="2"|[[Odds ratio]] = 1.25 (95% CI: 1.11-1.41)<br/>&bull; "each 10% increase in the proportion of time taking clopidogrel plus PPI during follow-up was associated with a higher risk"
Line 50: Line 55:
|rowspan="2"|[[Cohort study]] taken from TRITON-TIMI 38 [[randomized controlled trial]]s<ref name="pmid19726078"/><ref name="pmid19106084">{{cite journal| author=Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT et al.| title=Cytochrome p-450 polymorphisms and response to clopidogrel. | journal=N Engl J Med | year= 2009 | volume= 360 | issue= 4 | pages= 354-62 | pmid=19106084  
|rowspan="2"|[[Cohort study]] taken from TRITON-TIMI 38 [[randomized controlled trial]]s<ref name="pmid19726078"/><ref name="pmid19106084">{{cite journal| author=Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT et al.| title=Cytochrome p-450 polymorphisms and response to clopidogrel. | journal=N Engl J Med | year= 2009 | volume= 360 | issue= 4 | pages= 354-62 | pmid=19106084  
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19106084 | doi=10.1056/NEJMoa0809171 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref><ref name="pmid17982182">{{cite journal| author=Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S et al.| title=Prasugrel versus clopidogrel in patients with acute coronary syndromes. | journal=N Engl J Med | year= 2007 | volume= 357 | issue= 20 | pages= 2001-15 | pmid=17982182  
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19106084 | doi=10.1056/NEJMoa0809171 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref><ref name="pmid17982182">{{cite journal| author=Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S et al.| title=Prasugrel versus clopidogrel in patients with acute coronary syndromes. | journal=N Engl J Med | year= 2007 | volume= 357 | issue= 20 | pages= 2001-15 | pmid=17982182  
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17982182 | doi=10.1056/NEJMoa0706482 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref><br/>2 of 14 authors disclosed payments from AstraZenca, the maker of omeprazole and esomeprazole||rowspan="2"|6795 subjects with [[acute coronary syndrome]] who were randomized to the [[clopidogrel]] arm of the trial||rowspan="2"|33% (4529) were taking PPIs at randomization:<br/>&bull; 2814 took PPIs for duration of study<br/>&bull; 41% used [[pantoprazole]]<br/>&bull; 94% received [[stent]]s<br/>&bull; 47% received at least one drug eluting [[stent]]||rowspan="2"|Subjects not taking PPIs||rowspan="2"|Major vascular events || 11.8%||12.2%
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17982182 | doi=10.1056/NEJMoa0706482 }}</ref><br/>2 of 14 authors disclosed payments from AstraZenca, the maker of omeprazole and esomeprazole||rowspan="2"|6795 subjects with [[acute coronary syndrome]] who were randomized to the [[clopidogrel]] arm of the trial||rowspan="2"|33% (4529) were taking PPIs at randomization:<br/>&bull; 2814 took PPIs for duration of study<br/>&bull; 41% used [[pantoprazole]]<br/>&bull; 94% received [[stent]]s<br/>&bull; 47% received at least one drug eluting [[stent]]||rowspan="2"|Subjects not taking PPIs||rowspan="2"|Major vascular events || 11.8%||12.2%
|-
|-
| colspan="2"|&bull; Patients taking ''any'' PPI [[Hazards ratio|HR]] = 0.94, (95% CI 0.80–1.11)<br/>&bull; Patients taking ''any'' PPI for ''duration'' of study  [[Hazards ratio|HR]] = 1.05 (95% CI 0.85–1.30)<br/>&bull; Results similar for each individual PPI<br/>&bull; Results also insignificant when restricted to analysis of patients with a reduced function allele
| colspan="2"|&bull; Patients taking ''any'' PPI [[Hazards ratio|HR]] = 0.94, (95% CI 0.80–1.11)<br/>&bull; Patients taking ''any'' PPI for ''duration'' of study  [[Hazards ratio|HR]] = 1.05 (95% CI 0.85–1.30)<br/>&bull; Results similar for each individual PPI<br/>&bull; Results also insignificant when restricted to analysis of patients with a reduced function allele

Revision as of 22:10, 5 April 2010

This article is a stub and thus not approved.
Main Article
Discussion
Related Articles  [?]
Bibliography  [?]
External Links  [?]
Citable Version  [?]
 
This editable Main Article is under development and subject to a disclaimer.

In medicine, proton pump inhibitors (PPI) are medications that "inhibit H(+)-K(+)-exchanging atpase. They are used as anti-ulcer agents and sometimes in place of histamine H2 antagonists for gastroesophageal reflux disease."[1] They are also used to eradicate Helicobacter pylori, in combination with antibiotics.

Metabolism

Proton pump inhibitors are metabolized by the CYP2C19 isoenzyme of cytochrome P-450. Lanzoprazole is the strongest inhibitor of CYP2C19,[2] This may be less true for pantoprazole and esomeprazole.[3] Pantoprazole is the strongest inhibitor of the CYP2C9 isoenzyme[2]

Effectiveness

Proton pump inhibitors may improve:

PPIs may reduce the risk of gastrointestinal hemorrhage among patients undering anticoagulation.[9]

Adverse effects

Proton pump inhibitors may be associated with spontaneous bacterial peritonitis.[10] Recent starting of these drugs may also be associated with pneumonia acquired in the community[11] or hospital[12]. These drugs may be associated with Clostridium difficile diarrhea, and fractures.

Starting proton pump inhibitors in healthy volunteers may induce acid-related symptoms when PPIs are stopped[13] This is problematic considering how often PPIs are incorrectly prescribed.[14]

Proton pump inhibitors may induce acid-related symptoms in healthy volunteers after withdrawal, presumably due to rebound acid hypersecretion.[13]

Drug interactions

In the United States, the Food and Drug Administration has issued warnings regarding combining PPIs with clopidogrel.[15][16]

Studies of drug interactions between PPIs and clopidogrel[17][18][19][20][21]
Trial Patients Intervention Comparison Outcome Results
PPI Control
Tennessee Medicaid cohort study[17] 20,596 patients hospitalized for myocardial infarction, myocardial revascularization, or unstable angina pectoris 7593 concurrent users of clopidogrel and PPIs
• 62% used pantoprazole
13003 patients not taking PPIs Serious cardiovascular disease
"Serious cardiovascular disease was not increased; however, the 95% CI included a clinically important increased risk"
Ontario nested case-control study[18] 13,636 subjects taking clopidogrel after myocardial infarction 782 subjects readmitted for myocardial infarction 2057 subjects not readmitted Rate of PPI usage other than pantoprazole Odds ratio = 1.40 (95% CI 1.10–1.77)
Cohort study from the VA Cardiac Care Follow-up Clinical Study[19] 8205 subjects with acute coronary syndrome 64% were taking PPIs:
• 0.2% used pantoprazole
• 50% received stents
• Probably < 50% used drug eluting stents[22]
Subjects not taking PPIs Major vascular events 29.8% 20.8%
Odds ratio = 1.25 (95% CI: 1.11-1.41)
• "each 10% increase in the proportion of time taking clopidogrel plus PPI during follow-up was associated with a higher risk"
Cohort study taken from TRITON-TIMI 38 randomized controlled trials[20][23][24]
2 of 14 authors disclosed payments from AstraZenca, the maker of omeprazole and esomeprazole
6795 subjects with acute coronary syndrome who were randomized to the clopidogrel arm of the trial 33% (4529) were taking PPIs at randomization:
• 2814 took PPIs for duration of study
• 41% used pantoprazole
• 94% received stents
• 47% received at least one drug eluting stent
Subjects not taking PPIs Major vascular events 11.8% 12.2%
• Patients taking any PPI HR = 0.94, (95% CI 0.80–1.11)
• Patients taking any PPI for duration of study HR = 1.05 (95% CI 0.85–1.30)
• Results similar for each individual PPI
• Results also insignificant when restricted to analysis of patients with a reduced function allele
Medco cohort study[21] 16,718 subjects who took clopidogrel for 12 months after coronary stent 41% were taking PPIs:
• 24% used pantoprazole
• 100% received stents
• Unknown use of drug eluting stents
Subjects not taking PPIs Major vascular events 24% to 29% 17.9%
• Pantoprazole HR=1.61 (pantoprazole had most GI bleeding)
• Esooprazole HR=1.57
• Lansoprazole HR=1.39
• Omeprazole HR=1.39
Histamine H2 antagonists HR=1.14 (insignicant)

Proton pump inhibitors (especially inhibitors other than pantoprazole[18]), which are metabolized by the CYP2C19 isoenzyme of cytochrome P-450, may[19] or may not[20] increase adverse cardiac events when given to patients taking clopidogrel for coronary heart disease.

References

  1. Anonymous (2024), Proton pump inhibitor (English). Medical Subject Headings. U.S. National Library of Medicine.
  2. 2.0 2.1 Li XQ, Andersson TB, Ahlström M, Weidolf L (2004). "Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities.". Drug Metab Dispos 32 (8): 821-7. PMID 15258107.
  3. Siller-Matula JM, Spiel AO, Lang IM, Kreiner G, Christ G, Jilma B (January 2009). "Effects of pantoprazole and esomeprazole on platelet inhibition by clopidogrel". Am. Heart J. 157 (1): 148.e1–5. DOI:10.1016/j.ahj.2008.09.017. PMID 19081411. Research Blogging.
  4. Moayyedi P, Soo S, Deeks J, Delaney B, Innes M, Forman D (2006). "Pharmacological interventions for non-ulcer dyspepsia.". Cochrane Database Syst Rev (4): CD001960. DOI:10.1002/14651858.CD001960.pub3. PMID 17054151. Research Blogging. Review in: Evid Based Med. 2007 Jun;12(3):79
  5. van Pinxteren B, Numans ME, Bonis PA, Lau J (2006). "Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease.". Cochrane Database Syst Rev 3: CD002095. DOI:10.1002/14651858.CD002095.pub3. PMID 16855986. Research Blogging.
  6. Pace F, Tonini M, Pallotta S, Molteni P, Porro GB (2007). "Systematic review: maintenance treatment of gastro-oesophageal reflux disease with proton pump inhibitors taken 'on-demand'.". Aliment Pharmacol Ther 26 (2): 195-204. DOI:10.1111/j.1365-2036.2007.03381.x. PMID 17593065. Research Blogging. Review in: Evid Based Med. 2007 Dec;12(6):177 Review in: ACP J Club. 2007 Nov-Dec;147(3):69
  7. Bardhan KD, Müller-Lissner S, Bigard MA, Bianchi Porro G, Ponce J, Hosie J et al. (1999). "Symptomatic gastro-oesophageal reflux disease: double blind controlled study of intermittent treatment with omeprazole or ranitidine. The European Study Group.". BMJ 318 (7182): 502-7. PMID 10024259. PMC PMC27748.
  8. Khan M, Santana J, Donnellan C, Preston C, Moayyedi P (2007). "Medical treatments in the short term management of reflux oesophagitis.". Cochrane Database Syst Rev (2): CD003244. DOI:10.1002/14651858.CD003244.pub2. PMID 17443524. Research Blogging.
  9. Massó González EL, García Rodríguez LA (2008). "Proton pump inhibitors reduce the long-term risk of recurrent upper gastrointestinal bleeding: an observational study.". Aliment Pharmacol Ther 28 (5): 629-37. DOI:10.1111/j.1365-2036.2008.03780.x. PMID 18616644. Research Blogging.
  10. Bajaj JS, Zadvornova Y, Heuman DM, et al. (May 2009). "Association of proton pump inhibitor therapy with spontaneous bacterial peritonitis in cirrhotic patients with ascites". Am. J. Gastroenterol. 104 (5): 1130–4. DOI:10.1038/ajg.2009.80. PMID 19337238. Research Blogging.
  11. Sarkar M, Hennessy S, Yang YX. Proton-pump inhibitor use and the risk for community-acquired pneumonia. Ann Intern Med. 2008 Sep 16;149(6):391-8. PMID 18794558
  12. Herzig SJ, Howell MD, Ngo LH, Marcantonio ER. Acid-suppressive medication use and the risk for hospital-acquired pneumonia. JAMA. 2009 May 27;301(20):2120-8. PMID 19470989
  13. 13.0 13.1 Reimer C, Søndergaard B, Hilsted L, Bytzer P (2009). "Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy.". Gastroenterology 137 (1): 80-7, 87.e1. DOI:10.1053/j.gastro.2009.03.058. PMID 19362552. Research Blogging. Cite error: Invalid <ref> tag; name "pmid19362552" defined multiple times with different content
  14. Wohlt PD, Hansen LA, Fish JT (2007). "Inappropriate continuation of stress ulcer prophylactic therapy after discharge.". Ann Pharmacother 41 (10): 1611-6. DOI:10.1345/aph.1K227. PMID 17848420. Research Blogging.
  15. Anonymous. (2009) Early Communication about an Ongoing Safety Review of clopidogrel bisulfate (marketed as Plavix)
  16. Anonymous (11/17/2009) Information for Healthcare Professionals: Update to the labeling of Clopidogrel Bisulfate (marketed as Plavix) to alert healthcare professionals about a drug interaction with omeprazole (marketed as Prilosec and Prilosec OTC)
  17. 17.0 17.1 Ray WA, Murray KT, Griffin MR, Chung CP, Smalley WE, Hall K et al. (2010). "Outcomes with concurrent use of clopidogrel and proton-pump inhibitors: a cohort study.". Ann Intern Med 152 (6): 337-45. DOI:10.1059/0003-4819-152-6-201003160-00003. PMID 20231564. Research Blogging.
  18. 18.0 18.1 18.2 Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC, Tu JV et al. (2009). "A population-based study of the drug interaction between proton pump inhibitors and clopidogrel.". CMAJ 180 (7): 713-8. DOI:10.1503/cmaj.082001. PMID 19176635. PMC PMC2659819. Research Blogging. Review in: Ann Intern Med. 2009 Aug 18;151(4):JC2-13 Review in: Evid Based Med. 2009 Oct;14(5):154 Cite error: Invalid <ref> tag; name "pmid19176635" defined multiple times with different content
  19. 19.0 19.1 19.2 Ho PM, Maddox TM, Wang L, et al. (March 2009). "Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome". JAMA 301 (9): 937–44. DOI:10.1001/jama.2009.261. PMID 19258584. Research Blogging.
  20. 20.0 20.1 20.2 O'Donoghue ML, Braunwald E, Antman EM, Murphy SA, Bates ER, Rozenman Y et al. (2009). "Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials.". Lancet 374 (9694): 989-97. DOI:10.1016/S0140-6736(09)61525-7. PMID 19726078. Research Blogging. Cite error: Invalid <ref> tag; name "pmid19726078" defined multiple times with different content
  21. 21.0 21.1 Stanek EJ et al. (2009) A National Study of the Effect of Individual Proton Pump Inhibitors on Cardiovascular Outcomes in Patients Treated with Clopidogrel Following Coronary Stenting: The Clopidogrel Medco Outcomes Study Society for Cardiovascular Angiography and Interventions 2009 Annual Meeting
  22. Ho PM, Fihn SD, Wang L, Bryson CL, Lowy E, Maynard C et al. (2007). "Clopidogrel and long-term outcomes after stent implantation for acute coronary syndrome.". Am Heart J 154 (5): 846-51. DOI:10.1016/j.ahj.2007.08.028. PMID 17967588. Research Blogging.
  23. Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT et al. (2009). "Cytochrome p-450 polymorphisms and response to clopidogrel.". N Engl J Med 360 (4): 354-62. DOI:10.1056/NEJMoa0809171. PMID 19106084. Research Blogging.
  24. Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S et al. (2007). "Prasugrel versus clopidogrel in patients with acute coronary syndromes.". N Engl J Med 357 (20): 2001-15. DOI:10.1056/NEJMoa0706482. PMID 17982182. Research Blogging.