BACKGROUND: Most proton pump inhibitors inhibit the bioactivation of clopidogrel to its active metabolite. The clinical significance of this drug interaction is unknown. METHODS: We conducted a population-based nested case-control study among patients aged 66 years or older who commenced clopidogrel between Apr. 1, 2002, and Dec. 31, 2007, following hospital discharge after treatment of acute myocardial infarction. The cases in our study were those readmitted with acute myocardial infarction within 90 days after discharge. We performed a secondary analysis considering events within 1 year. Event-free controls (at a ratio of 3:1) were matched to cases on age, percutaneous coronary intervention and a validated risk score. We categorized exposure to proton pump inhibitors before the index date as current (within 30 days), previous (31-90 days) or remote (91-180 days). RESULTS: Among 13 636 patients prescribed clopidogrel following acute myocardial infarction, we identified 734 cases readmitted with myocardial infarction and 2057 controls. After extensive multivariable adjustment, current use of proton pump inhibitors was associated with an increased risk of reinfarction (adjusted odds ratio [OR] 1.27, 95% confidence interval [CI] 1.03-1.57). We found no association with more distant exposure to proton pump inhibitors or in multiple sensitivity analyses. In a stratified analysis, pantoprazole, which does not inhibit cytochrome P450 2C19, had no association with readmission for myocardial infarction (adjusted OR 1.02, 95% CI 0.70-1.47). INTERPRETATION: Among patients receiving clopidogrel following acute myocardial infarction, concomitant therapy with proton pump inhibitors other than pantoprazole was associated with a loss of the beneficial effects of clopidogrel and an increased risk of reinfarction.
BACKGROUND: Most proton pump inhibitors inhibit the bioactivation of clopidogrel to its active metabolite. The clinical significance of this drug interaction is unknown. METHODS: We conducted a population-based nested case-control study among patients aged 66 years or older who commenced clopidogrel between Apr. 1, 2002, and Dec. 31, 2007, following hospital discharge after treatment of acute myocardial infarction. The cases in our study were those readmitted with acute myocardial infarction within 90 days after discharge. We performed a secondary analysis considering events within 1 year. Event-free controls (at a ratio of 3:1) were matched to cases on age, percutaneous coronary intervention and a validated risk score. We categorized exposure to proton pump inhibitors before the index date as current (within 30 days), previous (31-90 days) or remote (91-180 days). RESULTS: Among 13 636 patients prescribed clopidogrel following acute myocardial infarction, we identified 734 cases readmitted with myocardial infarction and 2057 controls. After extensive multivariable adjustment, current use of proton pump inhibitors was associated with an increased risk of reinfarction (adjusted odds ratio [OR] 1.27, 95% confidence interval [CI] 1.03-1.57). We found no association with more distant exposure to proton pump inhibitors or in multiple sensitivity analyses. In a stratified analysis, pantoprazole, which does not inhibit cytochrome P450 2C19, had no association with readmission for myocardial infarction (adjusted OR 1.02, 95% CI 0.70-1.47). INTERPRETATION: Among patients receiving clopidogrel following acute myocardial infarction, concomitant therapy with proton pump inhibitors other than pantoprazole was associated with a loss of the beneficial effects of clopidogrel and an increased risk of reinfarction.
Authors: Douglas S Lee; Linda Donovan; Peter C Austin; Yanyan Gong; Peter P Liu; Jean L Rouleau; Jack V Tu Journal: Med Care Date: 2005-02 Impact factor: 2.983
Authors: Deepak L Bhatt; James Scheiman; Neena S Abraham; Elliott M Antman; Francis K L Chan; Curt D Furberg; David A Johnson; Kenneth W Mahaffey; Eamonn M Quigley Journal: Circulation Date: 2008-10-03 Impact factor: 29.690
Authors: David N Juurlink; Muhammad M Mamdani; Douglas S Lee; Alexander Kopp; Peter C Austin; Andreas Laupacis; Donald A Redelmeier Journal: N Engl J Med Date: 2004-08-05 Impact factor: 91.245
Authors: Jessica L Mega; Sandra L Close; Stephen D Wiviott; Lei Shen; Richard D Hockett; John T Brandt; Joseph R Walker; Elliott M Antman; William Macias; Eugene Braunwald; Marc S Sabatine Journal: N Engl J Med Date: 2008-12-22 Impact factor: 91.245
Authors: Tabassome Simon; Céline Verstuyft; Murielle Mary-Krause; Lina Quteineh; Elodie Drouet; Nicolas Méneveau; P Gabriel Steg; Jean Ferrières; Nicolas Danchin; Laurent Becquemont Journal: N Engl J Med Date: 2008-12-22 Impact factor: 91.245
Authors: Laura Y Park-Wyllie; David N Juurlink; Alexander Kopp; Baiju R Shah; Therese A Stukel; Carmine Stumpo; Linda Dresser; Donald E Low; Muhammad M Mamdani Journal: N Engl J Med Date: 2006-03-01 Impact factor: 91.245
Authors: P Savi; J M Herbert; A M Pflieger; F Dol; D Delebassee; J Combalbert; G Defreyn; J P Maffrand Journal: Biochem Pharmacol Date: 1992-08-04 Impact factor: 5.858
Authors: Atif Mohammad; Emmanouil S Brilakis; Rick A Weideman; Bertis B Little; Subhash Banerjee Journal: J Cardiovasc Transl Res Date: 2012-02-14 Impact factor: 4.132
Authors: Laura E Targownik; William D Leslie; K Shawn Davison; David Goltzman; Sophie A Jamal; Nancy Kreiger; Robert G Josse; Stephanie M Kaiser; Christopher S Kovacs; Jerilynn C Prior; Wei Zhou Journal: Am J Gastroenterol Date: 2012-07-10 Impact factor: 10.864