s-1743 and Cardiovascular-Diseases

Proton pump inhibitors (PPIs) are widely prescribed drugs for the treatment of gastroesophageal reflux disease (GERD). Several meta-analysis studies have reported associations between prolonged use of PPIs and major adverse cardiovascular events. However, interaction of PPIs with biological molecules involved in cardiovascular health is incompletely characterized. Dimethylarginine dimethylaminohydrolase (DDAH) is a cardiovascular enzyme expressed in cardiomyocytes, and other somatic cell types in one of two isotypes (DDAH1 and DDAH2) to metabolize asymmetric dimethylarginine (ADMA); a cardiovascular risk factor and competitive inhibitor of nitric oxide synthases (NOSs).. We performed high throughput drug screening of over 130,000 small molecules to discover human DDAH1 inhibitors and found that PPIs directly inhibit DDAH1. We expressed and purified the enzyme for structural and mass spectrometry proteomics studies to understand how a prototype PPI, esomeprazole, interacts with DDAH1. We also performed molecular docking studies to model the interaction of DDAH1 with esomeprazole. X-ray crystallography was used to determine the structure of DDAH1 alone and bound to esomeprazole at resolutions ranging from 1.6 to 2.9 Å.. Analysis of the enzyme active site shows that esomeprazole interacts with the active site cysteine (Cys273) of DDAH1. The structural studies were corroborated by mass spectrometry which indicated that cysteine was targeted by esomeprazole to inactivate DDAH1.. The inhibition of this important cardiovascular enzyme by a PPI may help explain the reported association of PPI use and increased cardiovascular risk in patients and the general population.. Our study calls for pharmacovigilance studies to monitor adverse cardiovascular events in chronic PPI users.

Topics: Amidohydrolases; Cardiovascular Diseases; Cysteine; Esomeprazole; Heart Disease Risk Factors; Humans; Molecular Docking Simulation; Proton Pump Inhibitors; Risk Factors

Aspirin and P2Y

Topics: Adenosine; Aspirin; Cardiovascular Diseases; Clopidogrel; Drug Administration Schedule; Drug Dosage Calculations; Drug Interactions; Esomeprazole; Gastrointestinal Hemorrhage; Gene Expression; Humans; Hydrogen-Ion Concentration; Peptic Ulcer; Prasugrel Hydrochloride; Proton Pump Inhibitors; Purinergic Antagonists; Receptors, Purinergic P2Y12; Ticagrelor; Ticlopidine

Low dose aspirin therapy plays a fundamental role in both the primary and secondary prevention of cardiovascular events. Although the evidence using low dose aspirin for secondary prevention is well-established, the decision to use aspirin for primary prevention is based on an evaluation of the patient's risk of cardiovascular events compared to their risk of adverse events, such as bleeding. In addition to the risk of bleeding associated with long term aspirin administration, upper gastrointestinal side effects, such as dyspepsia often lead to discontinuation of therapy, which places patients at an increased risk for cardiovascular events. One option to mitigate adverse events and increase adherence is the addition of esomeprazole to the medication regimen. This review article provides an evaluation of the literature on the concomitant use of aspirin and esomeprazole available through February 2013. The efficacy, safety, tolerability, cost effectiveness, and patient quality of life of this regimen is discussed. A summary of the pharmacokinetic and pharmacodynamic interactions between aspirin and esomeprazole, as well as other commonly used cardiovascular medications are also reviewed. The addition of esomeprazole to low dose aspirin therapy in patients at high risk of developing gastric ulcers for the prevention of cardiovascular disease, significantly reduced their risk of ulcer development. Pharmacokinetic and pharmacodynamic studies suggested that esomeprazole did not affect the pharmacokinetic parameters or the antiplatelet effects of aspirin. Therefore, for those patients who are at a high risk of developing a gastrointestinal ulcer, the benefit of adding esomeprazole likely outweighs the risks of longer term proton pump inhibitor use, and the combination can be recommended. Administering the two agents separately may also be more economical. On the other hand, for those patients at lower risk of developing a gastrointestinal ulcer, both the additional risk and cost make the inclusion of a proton pump inhibitor unwarranted.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; Cardiovascular Diseases; Cost-Benefit Analysis; Drug Combinations; Drug Costs; Esomeprazole; Female; Gastrointestinal Diseases; Humans; Male; Medication Adherence; Middle Aged; Patient Selection; Platelet Aggregation Inhibitors; Proton Pump Inhibitors; Quality of Life; Risk Factors; Treatment Outcome

The fixed-dose acetylsalicylic acid (ASA)/esomeprazole capsule combines the cardiovascular (CV) protective effects of low-dose ASA with the gastroprotective effects of the proton pump inhibitor esomeprazole. It is approved for use as a convenient once-daily regimen in the prevention of CV and cerebrovascular events in patients requiring continuous low-dose ASA who are at risk of developing gastric and/or duodenal (peptic) ulcers. In two large, 26-week, randomized, double-blind, multinational, phase III trials (ASTERIX and OBERON) in patients who were receiving low-dose ASA for the prevention of CV events and who had an increased risk of ulcer development, the incidence of endoscopy-proven peptic ulcers (primary endpoint) was significantly lower with the addition of esomeprazole 20 mg/day versus placebo. Moreover, patient-reported dyspeptic symptoms (epigastric pain and epigastric burning) were reported in significantly fewer patients in the low-dose ASA plus esomeprazole group than in the low-dose ASA plus placebo group. Low-dose ASA plus esomeprazole treatment was generally well tolerated, with a similar adverse event profile to that seen with low-dose ASA plus placebo.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Aspirin; Capsules; Cardiovascular Diseases; Drug Combinations; Esomeprazole; Humans; Peptic Ulcer; Platelet Aggregation Inhibitors; Prodrugs; Proton Pump Inhibitors

Low-dose aspirin (ASA, 75 - 325 mg/day) is widely used for the primary and secondary prevention of cardiovascular (CV) diseases. However, the value of primary prevention ASA is uncertain as the reduction in occlusive events needs to be weighed against the significant increase in major bleedings. Prevention with antisecretory drugs has been proposed to reduce the incidence of ASA-induced gastrointestinal (GI) bleedings, but non-adherence to gastro-protection is of concern, as it significantly increases the risk of upper GI adverse events. Beside patients and physicians education, one approach to overcome non-adherence is the development of fixed-dose combination.. This review explores the results of clinical studies on the influence of the combination esomeprazole (ESA) and ASA on pharmacokinetic (PK) parameters, and the role for such combination in prevention of CV events in patients at risk of gastric ulcers.. Patients at risk of ASA-induced gastroduodenal ulcer might benefit from a fixed ASA and proton pump inhibitor (PPI) combination. PK and PD parameters suggest there is no significant interaction between these drugs. Nevertheless, attention must be paid on the appropriate use of such combination, that is, still balancing the risk:benefit ratio in a real-life setting, and any increase in the proportion of patients receiving ASA and PPI should be considered as a warning signal.

Topics: Anti-Ulcer Agents; Aspirin; Cardiovascular Diseases; Drug Interactions; Esomeprazole; Humans; Peptic Ulcer; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic

The drug interaction between proton pump inhibitors and clopidogrel has been the subject of much study in recent years. Contradictory results regarding the effect of proton pump inhibitors on platelet reactivity and on clinical outcome in clopidogrel-treated patients have been reported in literature. Concomitant use of omeprazole and clopidogrel was found to decrease the exposure (AUC) to clopidogrel's active metabolite by 50% and to sharply increase platelet reactivity, as a result of inhibition by omeprazole of CYP2C19, a cytochrome P450 (CYP) enzyme. Pantoprazole has a much weaker effect on clopidogrel's pharmacokinetics and on platelet reactivity during concomitant use. The influence of the other proton pump inhibitors when used simultaneously with clopidogrel has not yet been investigated in adequately randomized studies. Regulatory agencies state that the combination of clopidogrel and the CYP2C19 inhibitors omeprazole and esomeprazole should be avoided. To date, there is no conclusive evidence of a clinically-relevant interaction between any of the proton pump inhibitors and clopidogrel.

Topics: Cardiovascular Diseases; Clopidogrel; Cytochrome P-450 Enzyme System; Drug Interactions; Drug Therapy, Combination; Esomeprazole; Gastrointestinal Hemorrhage; Humans; Omeprazole; Platelet Aggregation Inhibitors; Proton Pump Inhibitors; Ticlopidine

Low-dose acetyl salicylic acid (ASA) for preventing cardiovascular and cerebrovascular events is now one of the most frequently prescribed medications in some Western countries. However, it is associated with significant morbidity and mortality as a consequence of the development of gastric and duodenal ulcers and their complications. Recent randomized controlled trials in patients who are at moderately increased risk of ulcers have shown that the proton pump inhibitor esomeprazole (the S-isomer of racemic omeprazole) reduces the gastroduodenal ulcer incidence by approximately 70-85% and the gastrointestinal bleeding risk by as much as 90%. Case-control studies also indicate that the risk of ulcer bleeding is less in low-dose ASA users who concomitantly take a proton pump inhibitor. This article reviews the pharmacology of the component agents and the evidence for efficacy of the combination of esomeprazole and low-dose ASA.

Topics: Anti-Ulcer Agents; Aspirin; Cardiovascular Diseases; Cerebrovascular Disorders; Drug Therapy, Combination; Esomeprazole; Humans; Omeprazole; Peptic Ulcer; Randomized Controlled Trials as Topic; Risk

Clinical and basic mechanisms of interaction between Helicobacter pylori and its host have been the subject of numerous publications in the past year. Two additional proton pump inhibitors (PPIs), esomeprazole and rabeprazole, have shown effectiveness in H. pylori eradication when combined with amoxicillin and clarithromycin, and esomeprazole has demonstrated its effectiveness with only one daily dose. Other important recent developments worldwide include evidence-based treatment guidelines established at a European consensus meeting, improved accuracy in the urea breath test and the stool antigen test, new recommendations for second-line therapy, and a greater understanding of antimicrobial resistance in treatment failure. In addition, new studies have confirmed that H. pylori infection and use of nonsteroidal anti-inflammatory drugs or aspirin are the major causes of peptic ulcer disease and ulcer bleeding. This paper reviews the results of these studies and their implications for future research.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Amoxicillin; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Benzimidazoles; Cardiovascular Diseases; Clarithromycin; Drug Therapy, Combination; Enzyme Inhibitors; Esomeprazole; Helicobacter Infections; Helicobacter pylori; Humans; Peptic Ulcer; Rabeprazole; Stomach Neoplasms; Treatment Outcome

Recent studies suggest that proton pump inhibitor treatment may increase insulin secretion and improve glucose metabolism in type 2 diabetes. In a randomised double-blind prospective placebo-controlled 2 × 2 factorial study, we examined the effect of esomeprazole on insulin secretion, HbA(1c) and cardiovascular risk factors in type 2 diabetes.. Forty-one patients with type 2 diabetes using dietary control or oral glucose-lowering treatment were randomised to receive add-on esomeprazole 40 mg (n = 20) or placebo (n = 21) for 12 weeks. Randomisation was carried out prior to inclusion on the basis of a computer-generated random-number list. The allocation sequence was concealed in sealed envelopes from the researcher enrolling and assessing participants. The study was undertaken at Steno Diabetes Center, Gentofte, Denmark. The primary outcome was change in AUC for insulin levels during a meal test. Secondary outcomes were the levels of HbA(1c) and biochemical markers of cardiovascular risk, including lipids, coagulation factors, inflammation markers, markers of endothelial function and 24 h ambulatory BP measurements.. Forty-one participants were analysed. In the esomeprazole-treated group the AUC for insulin did not change (before vs after treatment: 28,049 ± 17,659 vs 27,270 ± 32,004 pmol/l × min (p = 0.838). In the placebo group AUC for insulin decreased from 27,392 ± 14,348 pmol/l × min to 22,938 ± 11,936 pmol/l × min (p = 0.002). Esomeprazole treatment (n = 20) caused a ninefold increase in the AUC for gastrin. HbA(1c) increased from 7.0 ± 0.6% (53 ± 5 mmol/mol) to 7.3 ± 0.8% (56 ± 6 mmol/mol) in the esomeprazole-treated group and from 7.0 ± 0.6% (53 ± 5 mmol/mol) to 7.4 ± 0.8% (57 ± 6 mmol/mol) in the placebo group (n = 21) (p for difference in change >0.05). Except for BP, there were no differences between the groups in the markers of cardiovascular risk (p > 0.05). Monitoring of 24 h ambulatory BP showed a significant decrease in daytime systolic BP, daytime diastolic BP and 24 h diastolic BP in the placebo group (p < 0.05). No change in BP was seen in the patients treated with esomeprazole.. Treatment with esomeprazole over 12 weeks did not improve insulin secretion, glycaemic control or cardiovascular disease biomarkers in patients with type 2 diabetes.

Topics: Aged; Biomarkers; Blood Pressure Monitoring, Ambulatory; Cardiovascular Diseases; Combined Modality Therapy; Denmark; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Esomeprazole; Gastrins; Glycated Hemoglobin; Humans; Hyperglycemia; Hypertension; Insulin; Insulin Secretion; Male; Middle Aged; Placebo Effect; Proton Pump Inhibitors; Risk Factors; Yogurt

Although low-dose acetylsalicylic acid (ASA) is recommended for prevention of cardiovascular events in at-risk patients, its long-term use can be associated with the risk of peptic ulcer and upper gastrointestinal (GI) symptoms that may impact treatment compliance. This prespecified secondary analysis of the OBERON study (NCT00441727) determined the efficacy of esomeprazole for prevention/resolution of low-dose ASA-associated upper GI symptoms. A post hoc analysis of predictors of symptom prevention/resolution was also conducted. Helicobacter pylori-negative patients taking low-dose ASA (75-325 mg) for cardiovascular protection who had ≥1 upper GI risk factor were eligible. The patients were randomized to once-daily esomeprazole 40 mg, 20 mg, or placebo, for 26 weeks; 2303 patients (mean age 67.6 years; 36% aged >70 years) were evaluable for upper GI symptoms. The proportion of patients with dyspeptic or reflux symptoms (self-reported Reflux Disease Questionnaire) was significantly lower (P < 0.0001) in those treated with esomeprazole versus in those treated with placebo. Treatment with esomeprazole (P < 0.0001), age >70 years (P < 0.01), and the absence of upper GI symptoms at baseline (P < 0.0001) were all factors associated with prevention/resolution of upper GI symptoms. Together, these analyses demonstrate that esomeprazole is effective in preventing and resolving patient-reported upper GI symptoms in low-dose ASA users at increased GI risk.

Topics: Age Factors; Aged; Anti-Ulcer Agents; Aspirin; Cardiovascular Diseases; Dose-Response Relationship, Drug; Double-Blind Method; Dyspepsia; Esomeprazole; Female; Gastroesophageal Reflux; Gastrointestinal Diseases; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Risk Factors; Secondary Prevention; Self Report; Upper Gastrointestinal Tract

Aspirin-related peptic ulcers are a common disorder. However, whether or not aspirin should be continued during treatment for aspirin-related ulcers remains unclear.. To compare esomeprazole alone with esomeprazole plus aspirin in the treatment of aspirin-related peptic ulcers and to investigate the independent factors associated with the failure of ulcer healing.. From January 2008 to July 2011, patients with aspirin-related peptic ulcers were randomized to receive esomeprazole (40 mg per day) alone or esomeprazole (40 mg per day) plus aspirin (100 mg per day) for 8 weeks. The subjects with Helicobacter pylori infection were treated with standard triple therapy. Follow-up endoscopy was carried out at the end of the 8th week. The primary end point was the healing of peptic ulcers.. In all, 178 patients (89 receiving esomeprazole alone and 89 receiving esomeprazole plus aspirin) were enrolled and underwent follow-up endoscopy. The healing rate of ulcers by modified intention-to-treat analysis was 82.5% (95% confidence interval (CI), 74.2-90.8%) among patients treated with esomeprazole alone and 81.5% (95% CI, 73.0-90.0%) among patients treated with esomeprazole plus aspirin (difference, 1.0%; 95% CI, -11.2 to 12.6%). The per-protocol analysis yielded similar results (healing rate: 83.1% vs. 83.8%, respectively; difference, 0.7%; 95% CI, -11.2 to 12.6%). Multivariate analysis disclosed that use of steroids during treatment (odds ratio: 5.6; 95% CI, 1.1-27.7%) was the only independent factor associated with the failure of ulcer healing.. The observed ulcer healing rates were comparable in the esomeprazole and esomeprazole-plus-aspirin groups, but the wide CIs do not rule out clinically meaningful differences of more than 10%.

Topics: Aged; Anti-Ulcer Agents; Aspirin; Cardiovascular Diseases; Chi-Square Distribution; Drug Therapy, Combination; Esomeprazole; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Peptic Ulcer; Platelet Aggregation Inhibitors; Risk Factors; Surveys and Questionnaires; Taiwan; Treatment Outcome

Concurrent therapy with a proton-pump inhibitor is a standard treatment for patients receiving aspirin who are at risk for ulcer. Current U.S. guidelines also recommend clopidrogel for patients who have major gastrointestinal intolerance of aspirin. We compared clopidogrel with aspirin plus esomeprazole for the prevention of recurrent bleeding from ulcers in high-risk patients.. We studied patients who took aspirin to prevent vascular diseases and who presented with ulcer bleeding. After the ulcers had healed, we randomly assigned patients who were negative for Helicobacter pylori to receive either 75 mg of clopidogrel daily plus esomeprazole placebo twice daily or 80 mg of aspirin daily plus 20 mg of esomeprazole twice daily for 12 months. The end point was recurrent ulcer bleeding.. We enrolled 320 patients (161 patients assigned to receive clopidogrel and 159 to receive aspirin plus esomeprazole). Recurrent ulcer bleeding occurred in 13 patients receiving clopidogrel and 1 receiving aspirin plus esomeprazole. The cumulative incidence of recurrent bleeding during the 12-month period was 8.6 percent (95 percent confidence interval, 4.1 to 13.1 percent) among patients who received clopidogrel and 0.7 percent (95 percent confidence interval, 0 to 2.0 percent) among those who received aspirin plus esomeprazole (difference, 7.9 percentage points; 95 percent confidence interval for the difference, 3.4 to 12.4; P=0.001).. Among patients with a history of aspirin-induced ulcer bleeding whose ulcers had healed before they received the study treatment, aspirin plus esomeprazole was superior to clopidogrel in the prevention of recurrent ulcer bleeding. Our finding does not support the current recommendation that patients with major gastrointestinal intolerance of aspirin be given clopidogrel.

Topics: Aged; Anti-Ulcer Agents; Aspirin; Cardiovascular Diseases; Clopidogrel; Double-Blind Method; Drug Therapy, Combination; Esomeprazole; Female; Humans; Male; Peptic Ulcer Hemorrhage; Platelet Aggregation Inhibitors; Prospective Studies; Proton Pump Inhibitors; Secondary Prevention; Ticlopidine

Low-dose aspirin (LDA) is used to prevent recurrent cardiovascular (CV) events, but is associated with upper gastrointestinal (GI) bleeding; concomitant use of a proton pump inhibitor (PPI) reduces this risk. This study aimed to assess the cost-effectiveness of vonoprazan compared with PPIs (lansoprazole and esomeprazole) in patients taking LDA for secondary prevention of CV events.Methods and Results: A Markov simulation model was developed to predict the number of GI bleeding and acute CV events using 3 strategies (vonoprazan+LDA, esomeprazole+LDA, and lansoprazole+LDA), which were translated into quality-adjusted life-years (QALYs) and costs. Transition probabilities and utilities were derived from the results of published literature, and medical costs were based on the Japanese National Health Insurance fee table and claims databases in 2020. Outcomes were projected over 30 years starting at age 65 years and discounted at 2% annually. Expected costs with esomeprazole 20 mg, lansoprazole 15 mg and vonoprazan 10 mg were JPY 1,225,657, JPY 943,930, and JPY 1,059,510, respectively. The QALY gain for vonoprazan vs. esomeprazole was 0.35, thus vonoprazan was dominant against esomeprazole. The QALY gain for vonoprazan vs. lansoprazole was 0.29 and the incremental cost-effectiveness ratio (ICER) was JPY 398,551, thus, vonoprazan was more cost-effective than lansoprazole.. Vonoprazan is dominant or cost-effective compared with esomeprazole and lansoprazole in patients taking LDA for secondary prevention of CV events.

Topics: Aged; Aspirin; Cardiovascular Diseases; Cost-Benefit Analysis; Esomeprazole; Gastrointestinal Hemorrhage; Humans; Japan; Lansoprazole; Proton Pump Inhibitors; Pyrroles; Secondary Prevention

The aim of this study was to investigate the effect of CYP2C19 polymorphism and co-therapy with esomeprazole on the antiplatelet efficacy of clopidogrel.. The antiplatelet efficacy of clopidogrel depends on CYP2C19 polymorphism or the co-administration of some kind of proton pump inhibitor (PPI).. CYP2C19 genotype and the residual platelet reactivity (RPR) were measured in 361 coronary heart disease patients (male, mean age 69yrs), and the risk of cardiovascular events over a 3-month follow-up was assessed to evaluate the impact of co-administration of esomeprazole during dual antiplatelet therapy with aspirin and clopidogrel.. The values of RPR did not differ between esomeprazole and non-esomeprazole groups (4389 ± 1112 versus 4079 ± 1355 AU·min, P=0.103). RPR value was higher in intermediate metabolizers (IM) than in extensive metabolizers (EM) (4089 ± 1252 versus 3697 ± 1215 AU·min P=0.012) and, similarly, higher in poor metabolizers (PM) than in IM (4884 ± 1027 versus 4089 ± 1252 AU·min, P<0.001). There were no differences in RPR between esomeprazole and non-esomeprazole groups according to CYP2C19 genotype (EM, 3954 ± 1192 versus 3645 ± 1220 AU·min, P=0.361; IM, 4401 ± 1063 versus 4051 ± 1271 AU·min, P=0.293; PM, 4917 ± 669 versus 4876 ± 1099 AU·min, P=0.907, respectively). There was also no difference in clinical outcomes between esomeprazole and non-esomeprazole groups in the three-month follow-up (0% versus 0.92%, P=0.487).. These results suggest that concomitant use of esomeprazole with clopidogrel is not associated with reduced antiplatelet efficacy of clopidogrel or increased risk of cardiovascular events, irrespective of CYP2C19 genotype.

Topics: Aged; Aspirin; Blood Platelets; Cardiovascular Diseases; Clopidogrel; Coronary Disease; Cytochrome P-450 CYP2C19; Esomeprazole; Ethnicity; Female; Follow-Up Studies; Genotype; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Polymorphism, Genetic; Prospective Studies; Proton Pump Inhibitors; Ticlopidine; Treatment Outcome

Proton pump inhibitors (PPIs) are gastric acid-suppressing agents widely prescribed for the treatment of gastroesophageal reflux disease. Recently, several studies in patients with acute coronary syndrome have raised the concern that use of PPIs in these patients may increase their risk of major adverse cardiovascular events. The mechanism of this possible adverse effect is not known. Whether the general population might also be at risk has not been addressed.. Plasma asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase. Elevated plasma ADMA is associated with increased risk for cardiovascular disease, likely because of its attenuation of the vasoprotective effects of endothelial nitric oxide synthase. We find that PPIs elevate plasma ADMA levels and reduce nitric oxide levels and endothelium-dependent vasodilation in a murine model and ex vivo human tissues. PPIs increase ADMA because they bind to and inhibit dimethylarginine dimethylaminohydrolase, the enzyme that degrades ADMA.. We present a plausible biological mechanism to explain the association of PPIs with increased major adverse cardiovascular events in patients with unstable coronary syndromes. Of concern, this adverse mechanism is also likely to extend to the general population using PPIs. This finding compels additional clinical investigations and pharmacovigilance directed toward understanding the cardiovascular risk associated with the use of the PPIs in the general population.

Topics: Amidohydrolases; Animals; Arginine; Biomarkers; Cardiovascular Diseases; Cells, Cultured; Disease Models, Animal; Endothelium, Vascular; Esomeprazole; Gastroesophageal Reflux; Humans; Lansoprazole; Male; Mice; Mice, Inbred C57BL; Nitric Oxide Synthase Type III; Proton Pump Inhibitors; Risk Factors; Vasodilation

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Esomeprazole; Humans; Hyperglycemia; Insulin; Insulin Secretion; Male; Proton Pump Inhibitors

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

Topics: Aged; Anti-Ulcer Agents; Aspirin; Cardiovascular Diseases; Clinical Trials as Topic; Clopidogrel; Double-Blind Method; Drug Therapy, Combination; Esomeprazole; Female; Humans; Male; Peptic Ulcer Hemorrhage; Platelet Aggregation Inhibitors; Prospective Studies; Proton Pump Inhibitors; Secondary Prevention; Ticlopidine