Proton pump inhibitor: Difference between revisions

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imported>Robert Badgett
imported>Robert Badgett
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| 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/>(0.2% used [[pantoprazole]])||rowspan="2"|Subjects not taking PPIs||rowspan="2"| Major vascular events|| 20.8%|| 29.8%
| 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]]||rowspan="2"|Subjects not taking PPIs||rowspan="2"| Major vascular events|| 20.8%|| 29.8%
|-
|-
| colspan="2"|[[Odds ratio]] = 1.25 (95% CI: 1.11-1.41)
| colspan="2"|[[Odds ratio]] = 1.25 (95% CI: 1.11-1.41)
|-
|-
| 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> || rowspan="2"|6795 subjects with [[acute coronary syndrome]] who were randomized to the [[clopidogrel]] arm of the trial||rowspan="2"| 33% were taking PPIs:<br/>&bull; 41% used [[pantoprazole]]<br/>&bull; 97.6 anglos||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=19106084 | doi=10.1056/NEJMoa0809171 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref> || rowspan="2"|6795 subjects with [[acute coronary syndrome]] who were randomized to the [[clopidogrel]] arm of the trial||rowspan="2"| 33% were taking PPIs:<br/>&bull; 41% used [[pantoprazole]]<br/>&bull; 97.6% anglos||rowspan="2"|Subjects not taking PPIs||rowspan="2"|Major vascular events || 11.8%|| 12.2%
|-
|-
| colspan="2"|[[Hazards ratio]] = 0.94 (95% CI 0.80–1.11)
| colspan="2"|[[Hazards ratio]] = 0.94 (95% CI 0.80–1.11)
|-
|-
| Medco [[cohort study]]<ref name="medco"/> || 16,718 subjects who took [[clopidogrel]] for 12 months after coronary [[stent]]|| 41% were taking PPIs:<br/>(24% used [[pantoprazole]])||Subjects not taking PPIs||&nbsp; || &nbsp;|| &nbsp;
| Medco [[cohort study]]<ref name="medco"/> || 16,718 subjects who took [[clopidogrel]] for 12 months after coronary [[stent]]|| 41% were taking PPIs:<br/>&bull; 24% used [[pantoprazole]]||Subjects not taking PPIs||&nbsp; || &nbsp;|| &nbsp;
|}
|}



Revision as of 23:03, 9 October 2009

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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."[1] They are also used as part of curative therapy for Helicobacter pylori, in combination with antibiotics.

Metabolism

Proton pump inhibitors are metabolized by the CYP2C19 isoenzyme of cytochrome P-450. This may be less true for pantoprazole and esomeprazole.[2]

Adverse effects

Proton pump inhibitors may be associated with spontaneous bacterial peritonitis.[3] Recent starting of these drugs may also be associated with pneumonia acquired in the community[4] or hospital[5]. These drugs may be associated with Clostridium difficile diarrhea, and fractures.

Starting proton pump inhibitors in healthy volunteers may induce acid-related symptoms PPIs are stopped[6] This is problematic considering how often PPIs are incorrectly prescribed.[7]

Drug interactions

Studies of drug interactions between PPIs and clopidogrel[8][9][10][11]
Trial Patients Intervention Comparison Outcome Results
PPI Control
Ontario nested case-control study[8] 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[9] 8205 subjects with acute coronary syndrome 64% were taking PPIs:
• 0.2% used pantoprazole
Subjects not taking PPIs Major vascular events 20.8% 29.8%
Odds ratio = 1.25 (95% CI: 1.11-1.41)
Cohort study taken from TRITON-TIMI 38 randomized controlled trials[10][12] 6795 subjects with acute coronary syndrome who were randomized to the clopidogrel arm of the trial 33% were taking PPIs:
• 41% used pantoprazole
• 97.6% anglos
Subjects not taking PPIs Major vascular events 11.8% 12.2%
Hazards ratio = 0.94 (95% CI 0.80–1.11)
Medco cohort study[11] 16,718 subjects who took clopidogrel for 12 months after coronary stent 41% were taking PPIs:
• 24% used pantoprazole
Subjects not taking PPIs      

Proton pump inhibitors (especially inhibitors other than pantoprazole[8]), which are metabolized by the CYP2C19 isoenzyme of cytochrome P-450, may[9] or may not[10] 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. 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.
  3. 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.
  4. 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
  5. 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
  6. 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.
  7. 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.
  8. 8.0 8.1 8.2 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
  9. 9.0 9.1 9.2 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.
  10. 10.0 10.1 10.2 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.
  11. 11.0 11.1 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
  12. 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.