Proton pump inhibitor: Difference between revisions
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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|| | | 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|| 29.8%|| 20.8% | ||
|- | |- | ||
| colspan="2"|[[Odds ratio]] = 1.25 (95% CI: 1.11-1.41) | | colspan="2"|[[Odds ratio]] = 1.25 (95% CI: 1.11-1.41) | ||
|- | |- | ||
| [[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|| 6795 subjects with [[acute coronary syndrome]] who were randomized to the [[clopidogrel]] arm of the trial|| 33% (4529) were taking PPIs at randomization:<br/>• 2814 took PPIs for duration of study<br/>• 41% used [[pantoprazole]]<br/>• 94% received [[stent]]s|||Subjects not taking PPIs||Major vascular events || colspan="2"|• Patients taking ''any'' PPI [[Hazards ratio|HR]] = 0.94, (95% CI 0.80–1.11)<br/>• Patients taking ''any'' PPI for ''duration'' of study [[Hazards ratio|HR]] = 1.05 (95% CI 0.85–1.30) | | 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/>• 2814 took PPIs for duration of study<br/>• 41% used [[pantoprazole]]<br/>• 94% received [[stent]]s||rowspan="2"|Subjects not taking PPIs||rowspan="2"|Major vascular events || 11.8%||12.2% | ||
|- | |||
| colspan="2"|• Patients taking ''any'' PPI [[Hazards ratio|HR]] = 0.94, (95% CI 0.80–1.11)<br/>• Patients taking ''any'' PPI for ''duration'' of study [[Hazards ratio|HR]] = 1.05 (95% CI 0.85–1.30) | |||
|- | |- | ||
| 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||Major vascular events|| colspan="2"|• Pantoprazole [[Hazard ratio|HR]]=1.61 (pantoprazole had most [[Gastrointestinal hemorrhage|GI bleeding]])<br/>• Esooprazole [[Hazard ratio|HR]]=1.57<br/>• Lansoprazole [[Hazard ratio|HR]]=1.39<br/>• Omeprazole [[Hazard ratio|HR]]=1.39<br/>• [[Histamine H2 antagonist]]s [[Hazard ratio|HR]]=1.14 ([[Statistical significance|insignicant]]) | | 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||Major vascular events|| colspan="2"|• Pantoprazole [[Hazard ratio|HR]]=1.61 (pantoprazole had most [[Gastrointestinal hemorrhage|GI bleeding]])<br/>• Esooprazole [[Hazard ratio|HR]]=1.57<br/>• Lansoprazole [[Hazard ratio|HR]]=1.39<br/>• Omeprazole [[Hazard ratio|HR]]=1.39<br/>• [[Histamine H2 antagonist]]s [[Hazard ratio|HR]]=1.14 ([[Statistical significance|insignicant]]) | ||
Revision as of 13:16, 21 October 2009
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. 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]
Adverse effects
Proton pump inhibitors may be associated with spontaneous bacterial peritonitis.[4] Recent starting of these drugs may also be associated with pneumonia acquired in the community[5] or hospital[6]. 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[7] This is problematic considering how often PPIs are incorrectly prescribed.[8]
Drug interactions
In the United States, the Food and Drug Administration has issued a warning regarding combining PPIs with clopidogrel.[9]
| Trial | Patients | Intervention | Comparison | Outcome | Results | |
|---|---|---|---|---|---|---|
| PPI | Control | |||||
| Ontario nested case-control study[10] | 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[11] | 8205 subjects with acute coronary syndrome | 64% were taking PPIs: • 0.2% used pantoprazole |
Subjects not taking PPIs | Major vascular events | 29.8% | 20.8% |
| Odds ratio = 1.25 (95% CI: 1.11-1.41) | ||||||
| Cohort study taken from TRITON-TIMI 38 randomized controlled trials[12][14][15] 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 |
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) | ||||||
| Medco cohort study[13] | 16,718 subjects who took clopidogrel for 12 months after coronary stent | 41% were taking PPIs: • 24% used pantoprazole |
Subjects not taking PPIs | Major vascular events | • 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[10]), which are metabolized by the CYP2C19 isoenzyme of cytochrome P-450, may[11] or may not[12] increase adverse cardiac events when given to patients taking clopidogrel for coronary heart disease.
References
- ↑ Anonymous (2024), Proton pump inhibitor (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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
- ↑ 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
- ↑ 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.
- ↑ 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.
- ↑ Anonymous. (2009) Early Communication about an Ongoing Safety Review of clopidogrel bisulfate (marketed as Plavix)
- ↑ 10.0 10.1 10.2 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
- ↑ 11.0 11.1 11.2 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.
- ↑ 12.0 12.1 12.2 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.
- ↑ 13.0 13.1 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
- ↑ 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.
- ↑ 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.