title: Prognosis of concomitant users of clopidogrel and proton-pump inhibitors in a high-risk population for upper gastrointestinal bleeding.
abstract: BACKGROUND
  It is unclear whether concomitant use of clopidogrel and proton-pump inhibitors (PPIs) increases the risk of recurrence of cardiovascular disease or death in patients at high risk of upper gastrointestinal (GI) bleeding.
  
  
  METHODS
  Based on the Swedish Patient Register, a cohort of cardiovascular disease (including acute myocardial infarction, stroke and angina, from 2006 to 2008) was selected from a population with any diagnosis of upper GI bleeding. Data on drug prescription was retrieved from the Prescribed Drug Register. Patients entered into the cohort after their first discharge for cardiovascular disease and were followed up to death, recurrence of cardiovascular disease, or 90 days. A Cox regression model was conducted and hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated to evaluate the risks among users of different drug prescriptions.
  
  
  RESULTS
  Patients who were current users of only PPIs (HR 2.02, 95% CI 1.19-3.44), only clopidogrel (HR 1.14, 95% CI 0.53-2.45) and nonusers of both (HR 2.36, 95% CI 1.39-4.00) were at a higher risk of death compared with patients with a concomitant use. Results were similar among 1779 patients who had any history of upper GI bleeding (HR 2.05, 95% CI 1.18-3.54; HR 1.25, 95% CI 0.57-2.72; HR 2.30, 95% CI 1.33-3.98, respectively).
  
  
  CONCLUSIONS
  Among patients at high risk of upper GI bleeding, those with a concomitant use of PPIs and clopidogrel were at a decreased risk of mortality, and possibly also a decreased risk of recurrence of cardiovascular disease.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.forename: Rickard
authors.initials: R
authors.lastname: Ljung
authors.forename: Jesper
authors.initials: J
authors.lastname: Lagergren
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 76 Stockholm, Sweden. yunxia.lu@ki.se.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000453:epidemiology*; D000077144:Clopidogrel; D015331:Cohort Studies; D004347:Drug Interactions; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000453:epidemiology*; D006801:Humans; D008297:Male; D010437:Peptic Ulcer / Q000188:drug therapy / Q000453:epidemiology*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011379:Prognosis; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D012306:Risk; D013548:Sweden / Q000453:epidemiology; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine
references.citation: J Gastroenterol. 2011 Jan;46(1):39-45
references.pmid: 20811753
references.citation: N Engl J Med. 2010 Nov 11;363(20):1909-17
references.pmid: 20925534
references.citation: Gastroenterology. 2011 Mar;140(3):791-8
references.pmid: 21144850
references.citation: Clin Med Insights Cardiol. 2010 Dec 01;4:117-28
references.pmid: 21151850
references.citation: Digestion. 2010;81(1):10-5
references.pmid: 20029203
references.citation: Gastroenterology. 2014 Jan;146(1):147-56; quiz e15-6
references.pmid: 24055278
references.citation: Aliment Pharmacol Ther. 2012 Jan;35(2):313-4
references.pmid: 22172084
references.citation: Am J Med. 2001 Oct 15;111(6):469-73
references.pmid: 11690573
references.citation: Intern Med. 2009;48(21):1847-8
references.pmid: 19881232
references.citation: Cleve Clin J Med. 2011 Jan;78(1):39-49
references.pmid: 21199906
references.citation: Aliment Pharmacol Ther. 2012 Jan;35(1):165-74
references.pmid: 22050009
references.citation: Ann Intern Med. 2010 Mar 16;152(6):337-45
references.pmid: 20231564
references.citation: J Am Coll Cardiol. 2008 Jan 22;51(3):256-60
references.pmid: 18206732
references.citation: Hepatogastroenterology. 2013 Jan-Feb;60(121):112-7
references.pmid: 22709912
references.citation: J Thromb Haemost. 2010 Dec;8(12):2624-41
references.pmid: 20831618
references.citation: Am Heart J. 2009 Jan;157(1):148.e1-5
references.pmid: 19081411
references.citation: Heart. 2013 Apr;99(8):520-7
references.pmid: 22851683
references.citation: Aliment Pharmacol Ther. 2010 Apr;31(8):810-23
references.pmid: 20102352
references.citation: Pharmacoepidemiol Drug Saf. 2011 Oct;20(10):1043-9
references.pmid: 21823195
references.citation: Dig Dis Sci. 2010 Jul;55(7):1964-8
references.pmid: 19731021
references.citation: Can J Gastroenterol. 2009 Apr;23(4):251-2
references.pmid: 19373416
references.citation: Aliment Pharmacol Ther. 2011 Jan;33(1):77-88
references.pmid: 21083580
references.citation: Aust Fam Physician. 2008 Sep;37(9):721-3, 725-6
references.pmid: 18797530
references.citation: CMAJ. 2009 Mar 31;180(7):713-8
references.pmid: 19176635
references.citation: Am J Cardiol. 2010 Jun 15;105(12):1705-9
references.pmid: 20538118
references.citation: Arch Intern Med. 2010 Apr 26;170(8):704-10
references.pmid: 20421557
references.citation: Am J Cardiol. 2010 Mar 15;105(6):833-8
references.pmid: 20211327
references.citation: Int J Cardiol. 2013 Aug 10;167(3):965-74
references.pmid: 22464478
references.citation: Aliment Pharmacol Ther. 2010 Sep;32(6):801-10
references.pmid: 20653635
references.citation: J Am Coll Cardiol. 2010 Jul 6;56(2):134-43
references.pmid: 20620727
references.citation: J Am Coll Cardiol. 2008 Sep 16;52(12):1038-9; author reply 1039
references.pmid: 18786491
references.citation: Drugs. 2008;68(7):925-47
references.pmid: 18457460
references.citation: Lancet. 2013 Jun 8;381(9882):2033-43
references.pmid: 23746903
references.citation: JAMA. 2004 Oct 20;292(15):1867-74
references.pmid: 15494585
references.citation: JAMA. 2009 Mar 4;301(9):937-44
references.pmid: 19258584
references.citation: Health Technol Assess. 2009 Jun;13(31):iii-iv, ix-xi, 1-77
references.pmid: 19573471
references.citation: Lancet. 2009 Sep 19;374(9694):989-997
references.pmid: 19726078
references.citation: Circulation. 2009 Dec 8;120(23):2322-9
references.pmid: 19933932
references.citation: Pharmacotherapy. 2012 Sep;32(9):809-18
references.pmid: 22744772
references.citation: Drug Saf. 2011 Jan 1;34(1):47-57
references.pmid: 21047145