Pantoprazole Does Not Influence the Antiplatelet Effect of Clopidogrel-A Whole Blood Aggregometry Study After Coronary Stenting

被引:54
作者
Neubauer, Horst [1 ]
Engelhardt, Andreas [1 ]
Krueger, Jan C. [1 ]
Lask, Sebastian [1 ]
Boergel, Jan [1 ]
Muegge, Andreas [1 ]
Endres, Heinz G. [2 ]
机构
[1] Ruhr Univ Bochum, St Josef Hosp, Ctr Cardiovasc, D-44791 Bochum, Germany
[2] Ruhr Univ Bochum, Dept Med Informat Biometry & Epidemiol, D-44791 Bochum, Germany
关键词
clopidogrel; proton pump inhibitors; pantoprazole; drug interaction; platelet aggregation; PROTON PUMP INHIBITORS; PLATELET REACTIVITY; DRUG-INTERACTION; CARDIOVASCULAR EVENTS; OMEPRAZOLE; THERAPY; INTERVENTION; RESISTANCE; ASPIRIN; PHARMACOKINETICS;
D O I
10.1097/FJC.0b013e3181e19739
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Recent attention has been drawn to a potential drug-drug interaction observed between clopidogrel and proton pump inhibitors (PPIs). However, this potential interaction may not be a class effect of PPIs. We investigated if pantoprazole, which has a different metabolism than omeprazole, diminishes the effectiveness of clopidogrel. Our study included 336 patients (mean age 64.6 years; 106 women) 48 hours after percutaneous coronary stent implantation with a loading dose of 600 mg clopidogrel hydrogensulfate and 500 mg aspirin, followed by 75 mg clopidogrel and 100 mg aspirin daily. Whereas 188 patients (59 women) were not given any PPI comedication, 122 patients received pantoprazole and 26 either omeprazole or esomeprazole. The platelet aggregation followed by impedance aggregometry (in Ohm) was induced by 5 mu mol/L adenosine diphosphate. The percentage of clopidogrel low-response (CLR) was similar between the non-PPI group [2.75 Ohm (confidence interval, CI: 2.25-3.26); 21.9% CLR] and the pantoprazole group [2.33 Ohm (CI: 1.79-2.87); 16.4% CLR] but higher in patients treated with omeprazole/esomeprazole (3.00 Ohm (CI: 1.49-4.51); 30.8% CLR). Multivariate regression analysis reveals that the risk of CLR in the pantoprazole comedication group was not increased compared with the group without any PPI [odds ratio 0.59 (CI: 0.31-1.13) 0.11]. Our data suggest that pantoprazole does not diminish the antiplatelet effectiveness of clopidogrel early after coronary stenting. Therefore, the use of pantoprazole seems preferable in patients treated with clopidogrel when a concomitant medication with a PPI is indicated.
引用
收藏
页码:91 / 97
页数:7
相关论文
共 41 条
[1]   IDENTIFICATION OF HUMAN LIVER CYTOCHROME-P450 ISOFORMS MEDIATING OMEPRAZOLE METABOLISM [J].
ANDERSSON, T ;
MINERS, JO ;
VERONESE, ME ;
TASSANEEYAKUL, W ;
TASSANEEYAKUL, W ;
MEYER, UA ;
BIRKETT, DJ .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1993, 36 (06) :521-530
[2]   Drug interaction studies with esomeprazole, the (S)-isomer of omeprazole [J].
Andersson, T ;
Hassan-Alin, M ;
Hasselgren, G ;
Röhss, K .
CLINICAL PHARMACOKINETICS, 2001, 40 (07) :523-537
[3]   Variability in individual responsiveness to clopidogrel - Clinical implications, management, and future perspectives [J].
Angiolillo, Dominick J. ;
Fernandez-Ortiz, Antonio ;
Bernardo, Esther ;
Alfonso, Fernando ;
Macaya, Carlos ;
Bass, Theodore A. ;
Costa, Marco A. .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2007, 49 (14) :1505-1516
[4]   ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents [J].
Bhatt, Deepak L. ;
Scheiman, James ;
Abraham, Neena S. ;
Antman, Elliott M. ;
Chan, Francis K. L. ;
Furberg, Curt D. ;
Johnson, David A. ;
Mahaffey, Kenneth W. ;
Quigley, Eamonn M. ;
Harrington, Robert A. ;
Bates, Eric R. ;
Bridges, Charles R. ;
Eisenberg, Mark J. ;
Ferrari, Victor A. ;
Hlatky, Mark A. ;
Kaul, Sanjay ;
Lindner, Jonathan R. ;
Moliterno, David J. ;
Mukherjee, Debabrata ;
Schofield, Richard S. ;
Rosenson, Robert S. ;
Stein, James H. ;
Weitz, Howard H. ;
Wesley, Deborah J. .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2008, 52 (18) :1502-1517
[5]  
BHATT DL, COGENT PROSPECTIVE R
[6]   Pharmacokinetic drug interaction profiles of proton pump inhibitors [J].
Blume, Henning ;
Donath, Frank ;
Warnke, Andre ;
Schug, Barbara S. .
DRUG SAFETY, 2006, 29 (09) :769-784
[7]   Pantoprazole - An update of its pharmacological properties and therapeutic use in the management of acid-related disorders [J].
Cheer, SM ;
Prakash, A ;
Faulds, D ;
Lamb, HM .
DRUGS, 2003, 63 (01) :101-132
[8]   Comparison of Omeprazole and Pantoprazole Influence on a High 150-mg Clopidogrel Maintenance Dose The PACA (Proton Pump Inhibitors And Clopidogrel Association) Prospective Randomized Study [J].
Cuisset, Thomas ;
Frere, Corinne ;
Quilici, Jacques ;
Poyet, Raphael ;
Gaborit, Benedicte ;
Bali, Laurent ;
Brissy, Olivier ;
Morange, Pierre-Emmanuel ;
Alessi, Marie-Christine ;
Bonnet, Jean-Louis .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2009, 54 (13) :1149-1153
[9]  
Food and Drug Administration, PUBL HLTH ADV UPD SA
[10]  
Geisler T, 2008, J THROMB HAEMOST, V6, P54