Effect of comedication with proton pump inhibitors (PPIs) on post-interventional residual platelet aggregation in patients undergoing coronary stenting treated by dual antiplatelet therapy.
ABSTRACT Currently, there is an intense debate about whether comedication with proton pump inhibitors (PPIs) weakens the antiplatelet effect of clopidogrel in patients undergoing coronary stent implantation. Competing mechanisms on the hepatic cytochrome 2C19 level are proposed. The aim of this study was to assess the impact of PPI treatment on clopidogrel response by measuring the ex vivo platelet aggregation in patients with coronary intervention.
1425 consecutive patients with symptomatic coronary artery disease undergoing percutaneous coronary intervention were enrolled in this single centre study. PPI comedication was defined as PPI intake > or =1 week prior to a 600 mg clopidogrel loading dose. PPI treatment was based on physician preference. Residual platelet aggregation (RPA) was measured by optical aggregometry. To correct for potential selection bias, propensity score matching was applied.
RPA was significantly higher in PPI-treated patients compared with non-PPI-users (final aggregation 34.0% vs. 29.8%, p<0.001). Low responder defined as RPA in the upper tertile were more often found in PPI-users. After adjustment for relevant confounders, PPI treatment was independently associated with higher RPA-levels.
We demonstrated that peri-procedural co-administration of PPIs significantly decreases the effect of clopidogrel on RPA. To assess if clopidogrel-PPI interaction results in a higher susceptibility for cardiovascular events remains subject to further investigations.
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ABSTRACT: Some clinical studies have demonstrated that the proton pump inhibitor (PPI) could decrease clopidogrel platelet response and increase major adverse cardiovascular events (MACE) in white or black subjects. However, that remains to be determined in Chinese patients. In this study, we sought to determine whether there could be an increased risk for developing MACE after concomitant use of dual antiplatelet therapy (DAT) and a PPI in Chinese patients treated with percutaneous coronary intervention (PCI) and stenting. This study was a 5-year, single-center, retrospective cohort analysis of eligible patients (n = 6188) who received DAT and a PPI concomitantly (defined as PPI users) before discharge and/or 12-month follow-up after discharge as compared with those who received DAT alone (also defined as non-PPI users, n = 1465). The incidence of recurrent MACE, such as myocardial infarction (MI), definite stent thromboses (ST), or cardiovascular death, was compared between the PPI users and non-users. PPI users had a significantly higher incidence of the MACE than non-users (13.9% vs. 10.6%; adjusted HR: 1.33; 95% CI: 1.12 - 1.57, P = 0.007). Stratified analysis revealed that concurrent use of DAT and a PPI was associated with a significantly increased risk for developing ST compared with DAT alone (1% vs. 0.4%; adjusted HR: 2.66, 95% CI: 1.16 - 5.87, P = 0.012). However, there were no significant differences in the risk of MI, cardiovascular death and other adverse events, regardless of combination of clopidogrel and a PPI. The study further suggests that concomitant use of DAT and a PPI may be associated with an increased risk for developing MACE, in particular definite ST, in Chinese PCI patients after discharge as compared with use of DAT alone.PLoS ONE 01/2014; 9(1):e84985. DOI:10.1371/journal.pone.0084985 · 3.53 Impact Factor
Conference Paper: A dynamic model of a water treatment unit[Show abstract] [Hide abstract]
ABSTRACT: For support of field medical units, the U.S. army is developing a self-contained waste water treatment system to produce portable water for use within the unit. To aid in developing the control strategy and the fault detection/fault isolation logic, a dynamic model of the system is being developed. The first phase of the effort is to develop models of the system's components, such a ultrafiltration, reverse osmosis, ozonation, etc. These models are then combined to obtain a model for the complete system. To the greatest extent possible, fundamental equations form the basis of the models. In determining coefficients for the models, the the data was obtained from the experiments that formed the basis of the design of a pilot plant version of the unit. To refine the model, this data is then supplemented by operational data from the pilot plant.Decision and Control including the 16th Symposium on Adaptive Processes and A Special Symposium on Fuzzy Set Theory and Applications, 1977 IEEE Conference on; 01/1977
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ABSTRACT: Antiplatelet therapy plays an important role in the treatment of cardiovascular disease. The combination of acetylsalicylic acid and clopidogrel is routine care in patients with acute coronary syndromes (ACS) or undergoing percutaneous coronary interventions (PCI). Although the effectiveness of antiplatelet therapy is well established, studies have shown interindividual variability in the response to both antiplatelet drugs. This variability in response results in complications at both ends of the therapeutic spectrum (bleeding or thrombosis). Common genetic variations and co-prescribed drugs modify the effectiveness of clopidogrel and acetylsalicylic acid. TH In this thesis, several common genetic variants in enzymes involved in the pharmacokinetics and –dynamics of clopidogrel and acetylsalicylic acid were found to modify the effectiveness of both drugs. Furthermore, the concomitant use of certain proton pump inhibitors, calcium channel blockers and sulfonylureas was associated with an impaired response to clopidogrel.