Clopidogrel With Proton Pump Inhibitors: Safe or Not?

Gastrointestinal (GI) bleeding is a serious complication associated with use of antiplatelet therapy, and proton pump inhibitors (PPIs) are known to be beneficial in decreasing such risk. Several studies in the recent past have suggested concerns regarding interaction between clopidogrel and PPIs, presumably due to inhibition of clopidogrel activity and thus attenuation of its antiplatelet activity. A web-based literature and guidelines search was done using the keywords "clopidogrel," "omeprazole," "proton pump inhibitors" and "interaction." Of the available results, relevant studies (n = 11) were then systematically reviewed and summarized. The studies were categorized based on their retrospective or prospective nature. Most of the retrospective, observational studies suggested a link between the 2; however, recent prospective studies have shown no interaction, as well as a positive influence of PPIs in preventing the GI side effects of antiplatelet therapy. There is currently insufficient clinical evidence to suggest interaction between clopidogrel and PPIs and decision to add PPI therapy to clopidogrel should be guided by its clinical indications rather than as a routine prophylactic measure.     

Impaired Esophageal Mucosal Integrity May Play a Causative Role in Patients With Nongastroesophageal Reflux Disease–Related Noncardiac Chest Pain

Baseline impedance (BI) measurement can be used to evaluate the status of the esophageal mucosa integrity. We hypothesized that impaired esophageal mucosal integrity may play a causative role in patients with nongastroesophageal reflux disease (non-GERD)–related noncardiac chest pain (NCCP). This retrospective study analyzed 24-hour multichannel intraluminal impedance-pH testing data from 77 patients with NCCP and 5 healthy volunteers. BI was calculated at 3 cm (distal esophagus) and 17 cm (proximal esophagus) above the lower esophageal sphincter. GERD was defined by the presence of pathologic acid exposure or reflux esophagitis. Among the 77 patients with NCCP, 16 (20.8%) were classified into the GERD-related NCCP group and 61 (79.2%) into the non-GERD-related NCCP group. BI (median, interquartile range) of the non-GERD-related NCCP group was lower than the control group at the proximal esophagus (2507 Ω, 2156–3217 vs 3855 Ω, 3238–4182, P = 0.001) but was similar at the distal esophagus. The GERD-related NCCP group showed lower BI than the control group at both the distal and proximal esophagus (2024 Ω, 1619–2308 vs 3203 Ω, 2366–3774, P = 0.007 and 2272 Ω, 1896–2908 vs 3855 Ω, 3238–4182, P = 0.003, respectively). At the distal esophagus, BI was lower in the GERD-related NCCP group than the non-GERD-related NCCP group (P = 0.002), whereas it did not differ between the 2 groups at the proximal esophagus. In conclusion, the mucosal integrity is impaired at the proximal esophagus in patients with non-GERD-related NCCP, which might be the pathogenic mechanism of NCCP.     

Low Grade Esophageal Eosinophilia in Adults: An Unrecognized Part of the Spectrum of Eosinophilic Esophagitis?

Background  

Eosinophilic esophagitis (EoE) is defined by a minimum of 15 eosinophils (eos) per high-powered field (HPF) on esophageal biopsy, along with esophageal symptoms and the exclusion of gastroesophageal reflux (GERD). The clinical significance of fewer eosinophils is unknown.     

Is the Proton Pump Inhibitor Test Helpful in Patients with Laryngeal Symptoms?

Background and Objectives

The association of gastroesophageal reflux disease (GERD) and laryngeal symptoms is not clear. We aimed to examine the symptomatic and endoscopic relations between GERD and laryngeal symptoms and also to evaluate the response to a 2-week proton pump inhibitor (PPI) trial.

Methods

Seventy-two patients experiencing persistent laryngeal symptoms ≥2/week were enrolled. The laryngeal symptoms using the 1-week laryngeal symptom score (LSS) and the typical reflux symptoms including heartburn and acid regurgitation were assessed. Transnasal-esophagogastroduodenoscopy (TN-EGD) and ambulatory 24-h esophageal pH monitoring were performed. The patients were classified into a GERD group and a non-GERD group. The GERD group was defined as the cases of the presence of typical reflux symptoms and/or reflux esophagitis and/or pathologic acid exposure. Patients were treated with 30 mg of lansoprazole bid for 14 days.

Results

Thirty-nine patients (54 %) were diagnosed with GERD on the basis of typical reflux symptoms, EGD, and/or pH testing. There was no significant association between the LSS and the presence of typical reflux symptoms. Also, the presence of laryngitis was not significantly related to reflux esophagitis. The 2-week PPI trial showed no significant difference in the improvement in laryngeal symptoms between the GERD and non-GERD groups.

Conclusions

There was no significant symptomatic and endoscopic association between GERD and laryngeal symptoms. Therefore, GERD does not appear to be the sole cause of these symptoms. Additionally, a 2-week PPI trial is not long enough to be a diagnostic tool in patients with laryngeal symptoms.     

The Association Between Beta-blocker and Renin–Angiotensin System Inhibitor Use After Heart Failure With Reduced Ejection Fraction Hospitalization and Outcomes in Older Patients

IntroductionBeta-blockers (BB) and renin–angiotensin system inhibitors (RASi) are foundational for the treatment of heart failure with reduced ejection fraction (HFrEF). However, given the increased risk of side effects in older patients, uncertainty remains as to whether, on net, older patients benefit as much as the younger patients studied in trials.Methods and ResultsUsing the Get With The Guidelines–Heart Failure registry linked with Medicare data, overlap propensity weighted Cox proportional hazard models were used to examine the association between BB and RASi use at hospital discharge and 30-day and 1-year outcomes among patients with HFrEF. Among the 48,711 patients (aged ≥65 years) hospitalized with HFrEF, there were significant associations between BB and/or RASi use at discharge and lower rates of 30-day and 1-year mortality, including those over age 85 (30-day hazard ratio 0.56, 95% confidence interval 0.45–0.70; 1-year hazard ratio 0.69, 95% confidence interval 0.61–0.78). In addition, the magnitude of benefit associated with BB and/or RASi use after discharge did not decrease with advancing age. Even among the oldest patients, those over age 85, with hypotension, renal insufficiency or frailty, BB and/or RASi use at discharge was still associated with lower 1-year mortality or readmission.ConclusionsAmong older patients hospitalized with HFrEF, BB and/or RASi use at discharge is associated with lower rates of 30-day and 1-year mortality across all age groups and the magnitude of this benefit does not seem to decrease with advancing age. These data suggest that, absent a clinical contraindication, BB and RASi should be considered in all patients hospitalized with HFrEF before or at hospital discharge, regardless of age.     

TLR4 rs1927911, but Not TLR2 rs5743708, Is Associated With Atherosclerotic Cerebral Infarction in the Southern Han Population: A Case–Control Study

The objective of this study was to explore the association of toll-like receptor (TLR) 4 rs1927911 and TLR2 rs5743708 with atherosclerotic cerebral infarction (ACI) and their effects on blood pressure, fasting blood glucose, and blood lipids in the Han population of Hunan Province.TLR4 rs1927911 and TLR2 rs5743708 were detected by polymerase chain reaction and restriction fragment length polymorphism in 170 patients with ACI and 149 healthy controls.Our results indicated that the genotype and allele frequencies of TLR4 rs1927911 were significantly different between ACI patients and controls, whereas those of TLR2 rs5743708 were not significantly different between the 2 groups. For TLR4 rs1927911, blood pressure, fasting blood sugar, and serum lipid levels were not significantly different among different genotypes in the ACI and control groups.The rs1927911 polymorphism of the TLR4 gene may be a risk factor for ACI in the Southern Han population of Hunan Province; however, it may not be associated with blood pressure, fasting blood sugar, or blood lipids.     

The ambulatory pH study is normal,but the patient is not—the importance of the symptoms index: Watson RGP,Tham TCK,Johnston BT,et al.Double Blind Crossover Placebo Controlled Study of Omeprazole in the Treatment of Patients With Reflux Symptoms and Physiologic Levels of Acid Reflux—The “Sensitive Oesophagus” Gut 1997;40:587–90

The authors conducted a double blind, crossover, placebo controlled trial of Omeprazole 20 mg twice daily versus placebo in patients with heartburn and regurgitation with normal esophagoscopy and esophageal acid exposure during ambulatory pH monitoring of less than 5% of the total monitoring time who had at least one symptom episode during the pH monitoring period. The authors calculated a symptom index using previously described cutoff of 50% as indicating positive or negative (1).Each crossover period was 4 wk and the trial was done in a randomized, double blind fashion. Patients completed the SF-36 Quality of Life questionnaire (a well-validated instrument that gives a score for each of eight quality of life parameters) at the start of the trial and at 4 and 8 wk. Heartburn and regurgitation were graded on a scale of 0–3 from absent to severe. Patients were also evaluated for other upper gastrointestinal symptoms, including epigastric discomfort, postprandial fullness, early satiety, anorexia, nausea, belching, vomiting, pain on swallowing, nocturnal cough, and nocturnal wheeze. Subjects were asked at 4 and 8 wk whether they were the same, better, or worse compared to the previous 4 wk and given a score of 0, +1, and −1, respectively. Alginate tablets were allowed, and the number used was recorded on a diary card. Patients also recorded symptom frequency on a daily diary card. Statistical comparisons were by paired sign tests, except for the Quality of Life tests which were done by paired t-tests.Over a 1-yr period, 44 of 244 patients (18%) were found to have an acid-sensitive esophagus. Nineteen were recruited for the study. Fifteen were excluded because of distance from the study sight, and the remaining 10 were excluded for reasons not revealed. Thirteen had positive symptom index and six negative. Six were men, 13 women, mean age was 41.7 yr. Two patients dropped out because of severe symptoms or unacceptable side effects. These two were regarded as treatment failures and included in the final analysis.Twelve of the 18 patients had a better overall improvement of symptoms with Omeprazole 20 mg bid compared to placebo (p < .01). Only one patient was worse on Omeprazole compared to placebo with five reporting no difference. Quality of Life scores showed improvement in parameters of bodily pain and vitality on Omeprazole compared to placebo with no difference in the other six scores (physical function, general health, emotional role, physical role, social function, mental health). Ten of 12 (83%) with a positive symptom index reported a better overall level of improvement with Omeprazole compared to placebo (p < .02). In the patients with a negative symptom index, there was no significant difference compared to the two groups. Heartburn and regurgitation decreased in the positive symptom index group (p < .01) on Omeprazole as did the average number of days per week when alginate tablets were needed. The average number of days per week with symptoms was 4.75 on Omeprazole and 5.8 on placebo (p < .01). Alginate tablets were used an average of 3 days per week in Omeprazole and 5.21 in the placebo group (p < .01). The other upper gastrointestinal symptoms showed no significant difference between the two treatment groups. It is of interest that Quality of Life scores improved significantly from baseline in vitality, social function, physical role, emotional role, and bodily pain on Omeprazole, but not on placebo.