s-1743 and Coronary-Artery-Disease

Coronary artery disease (CAD) patients experience chest pain (CP) from cardiac and non-cardiac etiologies.. Proton pump inhibitor (PPI) treatment of CAD patients with atypical CP would result in less CP, as well as fewer emergency room (ER) visits for CP, medical evaluations, and hospitalizations.. A randomized, prospective, placebo-controlled trial in patients with a history of severe CAD, without current ischemia, and not receiving acid reducing therapy. Patients received esomeprazole 40 mg or placebo daily added to standard cardiac medications for 6 months. The primary endpoint was percentage of patients experiencing CP.. In 162 patients randomized, 78 received esomeprazole and 84 received placebo. Esomeprazole significantly reduced the primary endpoint of patients experiencing CP (24.4% versus 54.8%; p < 0.001). The absolute number of CP episodes and CP days was also significantly reduced. Fewer patients experienced the combined endpoint of doctor office/ER visits for CP (19.2% versus 48.8%; p < 0.001), mainly due to significantly fewer office visits for CP (14.1% versus 39.3%; p < 0.001). ER visits for CP trended less with esomeprazole (12.8% versus 22.6%; p = 0.10), as did hospitalizations for CP (14.1% versus 20.2%; p = 0.30). However, the study lacked statistical power to reach these secondary endpoints.. Concomitant esomeprazole therapy in CAD patients without active ischemia but with a history of atypical CP reduces number of patients with further CP symptoms and medical office visits for CP. Larger studies are needed to further evaluate PPI treatment on ER CP visits and hospitalizations in this patient population.

Topics: Anti-Ulcer Agents; Chest Pain; Coronary Artery Disease; Drug Therapy, Combination; Esomeprazole; Female; Humans; Male; Middle Aged; Treatment Outcome

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 mmol/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.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Aged; Angioplasty, Balloon, Coronary; Aspirin; Clopidogrel; Coronary Artery Disease; Drug Interactions; Esomeprazole; Female; Humans; Male; Middle Aged; Multivariate Analysis; Omeprazole; Pantoprazole; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prospective Studies; Proton Pump Inhibitors; Regression Analysis; Stents; Ticlopidine

Patients receiving dual antiplatelet treatment with aspirin and clopidogrel are commonly treated with proton pump inhibitors (PPIs). Attenuating effects on platelet response to clopidogrel have been reported solely for the PPI omeprazole. PPIs differ in their metabolisation properties as well as their potential for drug-drug interactions. The aim of this study was to investigate the impact of different PPIs (pantoprazole, omeprazole, esomeprazole) on platelet response to clopidogrel in patients with previous coronary stent placement under chronic clopidogrel treatment. In a cross-sectional observational study, consecutive patients under clopidogrel maintenance treatment (n = 1,000) scheduled for a control coronary angiography were enrolled. Adenosine diphosphate (ADP)-induced platelet aggregation (in AU*min) was measured with multiple electrode platelet aggregometry (MEA). From the entire study population, 268 (26.8%) patients were under PPI treatment at the time point of platelet function testing (pantoprazole, n = 162; omeprazole, n = 64; esomeprazole, n = 42). Platelet aggregation (median [interquartile range]) was significantly higher in patients with omeprazole treatment (295.5 [193.5-571.2] AU*min) compared to patients without PPI treatment (220.0 [143.8-388.8] AU*min; p = 0.001). Platelet aggregation was similar in patients with pantoprazole (226.0 [150.0-401.5] AU*min) or esomeprazole (209.0 [134.8-384.8] AU*min) treatment compared to patients without PPI treatment (p = 0.69 and p = 0.88, respectively). Attenuating effects of concomitant PPI treatment on platelet response to clopidogrel were restricted to the use of omeprazole. No attenuating effects on platelet response to clopidogrel were observed for pantoprazole or esomeprazole. Specifically designed and randomized clinical studies are needed to define the impact of concomitant PPI treatment on adverse events after percutaneous coronary intervention.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adenosine Diphosphate; Aged; Angioplasty, Balloon, Coronary; Aspirin; Clopidogrel; Coronary Angiography; Coronary Artery Disease; Cross-Sectional Studies; Drug Interactions; Drug Therapy, Combination; Esomeprazole; Female; Humans; Male; Middle Aged; Multivariate Analysis; Omeprazole; Pantoprazole; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Proton Pump Inhibitors; Stents; Ticlopidine