s-1743 and Acute-Coronary-Syndrome

Little is known about the efficacy of proton pump inhibitors compared with H(2) receptor antagonists in preventing adverse upper gastrointestinal complications in patients with acute coronary syndrome (ACS) or ST elevation myocardial infarction (STEMI) receiving aspirin, clopidogrel, and enoxaparin or thrombolytics. The objective of this study was to compare the efficacies of esomeprazole and famotidine in preventing gastrointestinal complications.. A double-blind, randomized, controlled trial was performed in patients receiving a combination of aspirin, clopidogrel, and either enoxaparin or thrombolytics. Patients received either esomeprazole (20 mg nocte) or famotidine (40 mg nocte) orally for 4-52 weeks, depending on the duration of dual antiplatelet therapy. The primary end point was upper gastrointestinal bleeding (GIB), perforation, or obstruction from ulcer/erosion (http://www.clinicaltrials.gov NCT00683111).. In all, 311 patients were recruited, with 163 and 148 patients in the esomeprazole and famotidine groups, respectively. Mean (s.d.) follow-up was 19.2 (17.6) and 17.6 (18.0) weeks, respectively. One (0.6%) patient in the esomeprazole group and 9 (6.1%) in the famotidine group reached the primary end point (log-rank test, P=0.0052, hazard ratio=0.095, 95% confidence interval: 0.005-0.504); all had upper GIB.. In patients with ACS or STEMI, esomeprazole is superior to famotidine in preventing upper gastrointestinal complications related to aspirin, clopidogrel, and enoxaparin or thrombolytics.

Topics: Acute Coronary Syndrome; Aged; Anti-Ulcer Agents; Aspirin; Chi-Square Distribution; Clopidogrel; Double-Blind Method; Drug Therapy, Combination; Enoxaparin; Esomeprazole; Famotidine; Female; Fibrinolytic Agents; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Intestinal Perforation; Male; Middle Aged; Platelet Aggregation Inhibitors; Proportional Hazards Models; Ticlopidine; Treatment Outcome

Pharmacokinetic studies suggest that clopidogrel and esomeprazole are metabolized by similar hepatic enzymes; however, previous studies have not identified a biochemical interaction.. To determine whether addition of esomeprazole to patients receiving aspirin and clopidogrel reduces the antiplatelet effects of clopidogrel.. Patients with a history of an acute coronary syndrome who had previously received clopidogrel were recruited. Subjects were commenced on clopidogrel and randomized to one of two treatment arms (esomeprazole or placebo) for 6 weeks. Following a 2-week washout period for study medications, patients were crossed over onto the alternative treatment arm for a further 6 weeks. Platelet function tests were undertaken at baseline, following the first treatment period, after washout and following the second treatment period.. Thirty-one patients were enrolled. Significant attenuation of clopidogrel's antiplatelet effects was seen with co-administration of esomeprazole compared with placebo. Vasodilator stimulated phosphoprotein (VASP), platelet aggregometry (area under the curve (AUC)) and VerifyNow results were 54.7% ± 2.8 platelet reactivity index (PRI), 66.3 ± 2.6 AUC units and 213.1 ± 14.1 platelet reactivity units (PRU) with esomeprazole vs. 47% ± 2.7 PRI, 59.7 ± 3.7 AUC units and 181.4 ± 14.6 PRU with placebo (P < 0.01 esomeprazole vs. placebo for all measures). There was no significant difference in platelet aggregometry (maximal aggregation) between the esomeprazole group (68.9% ± 2.7 units) and placebo-treated group (64.5% ± 4.1 units; P > 0.05).. Esomeprazole when co-administered with aspirin and clopidogrel results in a significant attenuation of clopidogrel's antiplatelet effects.

Topics: Acute Coronary Syndrome; Aged; Aryl Hydrocarbon Hydroxylases; Aspirin; Blood Platelets; Cell Adhesion Molecules; Clopidogrel; Cross-Over Studies; Cytochrome P-450 CYP2C19; Double-Blind Method; Drug Interactions; Drug Therapy, Combination; Esomeprazole; Female; Genotype; Humans; Male; Microfilament Proteins; Middle Aged; Phenotype; Phosphoproteins; Placebo Effect; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Proton Pump Inhibitors; Risk Assessment; Ticlopidine; Time Factors; Victoria

Previous studies showed that esomeprazole does not interfere significantly with the platelet inhibitory effect of clopidogrel. It is unknown whether famotidine, a histamine 2 receptor antagonist, interacts with clopidogrel. This double-blind, randomized study aimed to compare the influence of esomeprazole and famotidine on the platelet inhibitory effect of clopidogrel.. Patients with acute coronary syndrome or elective percutaneous coronary interventions treated with aspirin and clopidogrel cotherapy were randomized to receive esomeprazole 20 mg daily or famotidine 40 mg daily. Platelet reactivity units (PRUs) were measured at baseline and on day 28. The primary analysis involved the PRU values on day 28.. There were 44 patients in the esomeprazole group and 44 in the famotidine group. The baseline PRUs of the 2 groups were comparable (esomeprazole vs famotidine, 229.1 ± 85.6 vs 220.4 ± 83.0, P = .63). The PRUs on day 28 were 242.6 ± 89.7 and 237.5 ± 79.2 in the groups receiving esomeprazole and famotidine, respectively (mean difference 5.1, 95% CI -30.8 to 41.0, P = .78).. The platelet inhibitory effect of clopidogrel was not significantly different between patients receiving esomeprazole and those receiving famotidine. Neither esomeprazole nor famotidine reduced the platelet inhibitory effect of clopidogrel. (Clinicaltrial.gov Identifier NCT01062516).

Topics: Acute Coronary Syndrome; Anti-Ulcer Agents; Blood Platelets; Clopidogrel; Double-Blind Method; Esomeprazole; Famotidine; Female; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Prospective Studies; Ticlopidine; Treatment Outcome

The Food and Drug Administration and the European Medicines Agency sent a warning in 2010 discouraging the concomitant use of clopidogrel with omeprazole or esomeprazole. The purpose is to know the gastroprotective approach in patients with acute coronary syndrome (ACS) and the level of follow-up of the alert. In 17 hospitals with catheterization laboratory in Spain, 1 per region, we studied 25 consecutive patients per hospital whose diagnosis of discharge since October 1, 2013, had been any type of ACS. We analyzed their baseline clinical profile, the gatroprotective agents at admission and discharge and the antiplatelet therapy at discharge. The number of patients included was 425: age 67.2 ± 12.5 years, women 29.8%, diabetes 36.5%. The patients presented unstable angina in 21.6%, non-ST-elevation myocardial infarction in 35.3% and ST-elevation myocardial infarction in 43.1%. Conservative approach was chosen in 17.9%, bare-metal stents 32.2%, ≥ 1 drug-eluting stent 48.5%, and surgery 1.4%. Aspirin was indicated in 1.9%, aspirin + clopidogrel 73.6%, aspirin + prasugrel 17.6%, and aspririn + ticagrelor 6.8%. Gastroprotective agents were present in 40.2% patients at admission and this percentage increased to 93.7% at discharge. Of the 313 (73.6%) on clopidogrel in 96 (30.6%) was combined with omeprazole and 3 (0.95%) with esomeprazole, whereas the most commonly used was pantoprazole with 190 patients (44.7%). In conclusion, almost the totality of the patients with an ACS receive gastroprotective agents at the moment of discharge, most of them with proton-pump inhibitors. In one every 3 cases of the patients who are on clopidogrel, the recommendation of the Food and Drug Administration and the European Medicines Agency is not followed.

Topics: Acute Coronary Syndrome; Aged; Clopidogrel; Dose-Response Relationship, Drug; Drug Therapy, Combination; Esomeprazole; Female; Gastrointestinal Diseases; Humans; Male; Platelet Aggregation Inhibitors; Proton Pump Inhibitors; Retrospective Studies; Ticlopidine; Treatment Outcome

There is conflicting evidence regarding the potential interaction between clopidogrel and proton pump inhibitors (PPIs), with observational studies suggesting an increased risk of adverse cardiovascular (CV) outcomes and clinical trials suggesting there is no such risk.. We conducted a retrospective cohort study to assess CV outcomes of 9753 patients taking dual antiplatelet therapy of aspirin plus clopidogrel with or without a PPI after hospitalization for acute coronary syndrome (ACS). Cox proportional hazards models were used to assess our primary endpoint of re-hospitalization for ACS in overall sample and a propensity score matching subsample.. Among patients taking clopidogrel plus aspirin, concomitant use of PPI was not associated with the risk of re-hospitalization for ACS (adjusted hazard ratio [HR] 1.12 [95%CI 0.72-1.73]). The findings were consistent in the propensity score matching cohort (adjusted HR 0.82 [95%CI 0.43-1.54]). Compared with PPI nonusers, there is no significant association between each specific PPI users and the risk of re-hospitalization for ACS (adjusted HR; omeprazole 0.96 [95%CI 0.35-2.66], pantoprazole 1.05 [95%CI 0.38-2.92], rabeprazole 0.60 [95%CI 0.17-2.17], esomeprazole 0.31 [95%CI 0.10-0.99], and lansoprazole 0.82 [95%CI 0.32-2.07]).. In conclusion, this population-based cohort study found that concomitant use of clopidogrel and PPI in patients who received dual antiplatelet therapy after ACS was not associated with risk of ACS re-hospitalization. Together, our study and findings of recently published clinical trials suggest that there was no apparent CV interaction between clopidogrel and PPI in patients who received dual antiplatelet therapy.

Topics: Acute Coronary Syndrome; Aged; Aryl Hydrocarbon Hydroxylases; Aspirin; Cardiovascular Diseases; Clopidogrel; Cohort Studies; Cytochrome P-450 CYP2C19; Databases, Factual; Drug Interactions; Esomeprazole; Female; Herb-Drug Interactions; Hospitalization; Humans; Male; Middle Aged; Omeprazole; Platelet Aggregation Inhibitors; Proton Pump Inhibitors; Recurrence; Retrospective Studies; Ticlopidine; Treatment Outcome