Proton Pump Inhibitors In Patients Research Articles

Expert position paper on the use of proton pump inhibitors in patients with cardiovascular disease and antithrombotic therapy

The ESC NSTEMI and STEMI guidelines1,2 and an ACCF/ACG/AHA consensus document3 recommend treatment with proton pump inhibitors (PPIs) in patients treated with dual antiplatelet treatment (DAPT) during the initial phase of an acute coronary syndrome (ACS) (ESC Class 1A recommendation), particularly in patients with a history of GI bleeding or peptic ulcer. Several studies have raised concerns that many PPIs, especially omeprazole, might diminish the antiplatelet effects of clopidogrel, most likely through inhibition of CYP2C19 and, consequently, the conversion of clopidogrel into its active metabolite.4,5 The aim of this position paper is to review the pharmacokinetic background of the interactions between these drugs, and their consequences on clinical outcomes, and to present suggestions for management of this important issue. Several agents widely used in patients on acetylsalicylic acid (ASA) may interact with the antiplatelet effects of ASA, but none through the CYP2C9 pathway by which ASA is metabolized. Recently, it has been reported that concomitant use of PPIs reduces the protective efficacy of ASA in patients with ischaemic heart disease.6,7 A case–control study investigated the antiplatelet effect of ASA in 418 ASA-treated CVD patients, 54 of whom were also treated with PPIs.7 Patients receiving PPIs had reduced antiplatelet effect of ASA, as shown by greater residual platelet aggregation responses. However, interaction between PPI and ASA is controversial.8 Potential clinical implications of these findings were explored by a registry study in a large population of ASA-treated patients with first time myocardial infarction.6 Even after adjusting for baseline variables with multivariate analysis and propensity score matching, PPI use was still significantly associated with ∼50% more ischaemic cardiovascular events. A sensitivity analysis showed no increase in risk related to the use of H2 receptor blockers.6 Suggested explanations for the …

High or Nonhigh Doses of Proton Pump Inhibitors for Patients with Peptic Ulcer Bleeding?

I read with interest the article entitled “A real world report on intravenous high-dose and nonhigh-dose proton pump inhibitors therapy in patients with endoscopically treated high-risk peptic ulcer bleeding” [1]. In this study, Lu et al. retrospectively analyzed patients receiving nonhighdose (80 mg pantoprazole i.v. bolus followed by i.v. 80 mg per day for 3 days) and high-dose proton pump inhibitors (PPI, 80 mg pantoprazole i.v. bolus followed by 8 mg per hr for 3 days) after obtaining initial hemostasis. After performing case-control matching, they found no statistical difference between the high-dose and nonhigh-dose groups. Therefore, they suggest that both doses of PPI were similar in reducing rebleeding in high-risk patients after successful endoscopic therapy. This conclusion is different from that in the consensus conference and also in our study [2, 3]. There are several key points that deserve to be mentioned with regards to this study. Lu's analysis is a retrospective study. Therefore, some important clinical variables could not be adjusted evenly between both groups. As a practice, doctors tend to use a high-dose PPI in high-risk patients after obtaining initial hemostasis. This point is demonstrated in Lu's study, Table 3. The number of patients with shock is more in the high-dose PPI group than that in the nonhigh-dose group (61.4% versus 46%). In Lu's study, the rebleeding rate for the high-dose group (19/70, 27.1%) is much higher than our series (2/50, 4%) and another report (8/120, 6.7%) [2, 4]. This phenomenon may be explained by the high percentage of patients with renal impairment (35/70, 50%). The high proportion of enrolled patients with renal impairment is unusual as compared to the past reports. Because three days after endoscopic therapy are a critical period, high-dose PPI is needed for these three days. After three days, patients usually receive oral intake. However, in Lu's study, they still gave 80 mg i.v. per day after three days. Thus, utilizing such therapy may waste some economic resources. In recent few years, there have been some articles supporting the use of low-dose PPI in high-risk patients after endoscopic hemostasis [5]. Many of these articles have pitfalls related to study design, such as the inclusion of patients with low-risk stigmata and the injection of epinephrine alone [6]. In vitro studies revealed that the acid environment impairs platelet function and clot stabilization [7]. Therefore, elevation of intragastric pH is mandatory to prevent rebleeding in patients with peptic ulcer bleeding, which has been confirmed in the consensus conference [2]. In our previous study, we obtained a markedly low rebleeding rate (4%) with a high-dose IV PPI [3]. Further, we found that different IV doses of PPIs have different rebleeding rates (omeprazole 160 mg/day: 9%, 6/67; 80 mg/day: 21.2%, 14/66) [8]. Clearly, there is a bit of a grey zone in identifying stigmata of recent hemorrhage (SRH) [9]. Misinterpretation of SRH can occur for a number of reasons, such as doctors' experience and academic judgement. Therefore, one strict design (double blind study) is favored in such a clinical trial.

Correlation between Ambulatory 24 Hour Dual Probe pH Monitoring and Reflux Finding Score, Reflux Symptom Index in the Laryngopharyngeal Reflux

Received June 25, 2013 Revised August 3, 2013 Accepted August 19, 2013 Address for correspondence Kyung Tae, MD Department of OtolaryngologyHead and Neck Surgery, College of Medicine, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 133-792, Korea Tel +82-2-2290-8585 Fax +82-2-2293-3335 E-mail kytae@hanyang.ac.kr Background and ObjectivesZZA 24-hour ambulatory dual probe for pH monitoring is the most specific and sensitive test for laryngopharyngeal reflux (LPR) disease. However, the use of this probe is not well tolerated in some patients due to discomfort and the invasive nature of the procedure. Thus, the diagnosis of LPR is usually made according to symptomatic responses to empirical treatment using a proton-pump inhibitor for patients with high score of reflux symptom index (RSI) and reflux finding score (RFS). The aim of this study is to evaluate the relationship between the RSI and RFS and pH monitoring using a 24-hour ambulatory dual probe, and determine the role of RSI and RFS in the diagnosis of LPR. Subjects and MethodZZWe studied 100 patients who underwent pH monitoring using a 24hour dual probe because of laryngopharyngeal reflux related symptoms or laryngoscopic findings. The various parameters of the 24-hour dual probe pH monitoring were compared with the scores of RSI and RFS. ResultsZZIn 24-hour dual probe pH monitoring, 64 of 100 patients tested positive for LPR. The mean of RSI score was significantly higher in the positive LPR group than in the negative group. However, RFS did not differ between the two groups. RSI scores were significantly associated with the reflux number in the upright position of the 24-hour dual probe pH monitoring. There was no correlation between RFS and the parameters of the 24-hour dual probe pH monitoring. ConclusionZZRSI can be a reliable diagnostic tool for laryngopharyngeal reflux disease instead of the 24-hour ambulatory dual probe pH monitoring. Korean J Otorhinolaryngol-Head Neck Surg 2013;56:706-10

Gastroesophageal reflux disease with laryngopharyngeal manifestation in Korea.

Globus pharyngeus and hoarseness are common extraesophageal manifestations inpatients with gastroesophageal reflux disease. The aim of this study was to evaluate the clinical characteristics, laryngoscopic findings, endoscopic findings, and response to proton pump inhibitors in patients presenting laryngeal symptoms suspected to be caused by GERD. We retrospectively reviewed the medical records of 160 patients that presented with globus and/or hoarseness and underwent acid suppression therapy under the impression of GERDfrom May 2003 to April 2009. Sixty patients(37.5%) reported classical GERD symptoms such as heartburn and/or acid regurgitation. Sixty nine percent(69%) of patients (95/138) showed abnormal laryngoscopic findings such as laryngeal edema/hyperemia, vocal cord swelling/hyperemia, arytenoids swelling/hyperemia, vocal cord nodule, vocal cord polyp, post-glottic swelling/hyperemia, etc. Endoscopically, 41.9%(39/93) showed normal endoscopic findings and 49.5% (46/93) showed minimal changes. 8.6% (8/93)of patients showed erosive reflux disease. Therapeutic response was not significantly different among patients treated with standard dose PPIs (44/58, 75.9%),half dose PPIs (17/22, 77.3%), or revaprazan (18/21,85.7%). Among patients with globus pharyngeus and/or hoarseness and suspected GERD, only 37.5% reported classical symptoms of GERD such as heartburn and/or acid regurgitation, 69% showed ab-normal laryngoscopic findings, 58.1% showed abnormal endoscopic findings, and 80% showed therapeutic response to acid suppression therapy.

Cardiovascular outcomes associated with concomitant use of clopidogrel and proton pump inhibitors in patients with acute coronary syndrome in Taiwan

Conflicting results have been reported regarding the increased risk of adverse outcomes in the concomitant use of clopidogrel and proton pump inhibitors (PPIs) compared with the use of clopidogrel alone. Our study indicated no statistically significant increase in the risk of rehospitalization for acute coronary syndrome due to concurrent use of clopidogrel and PPIs in an Asian population with higher prevalence of CYP2C19 intermediate and poor metabolizers. Among all PPIs, only omeprazole was found to be statistically significantly associated with an increased risk of rehospitalization for acute coronary syndrome. AIMS Our study aimed to examine the impact of concomitant use of proton pump inhibitors (PPIs) with clopidogrel on the cardiovascular outcomes of patients with acute coronary syndrome (ACS). Furthermore, we sought to quantify the effects of five individual PPIs when used concomitantly with clopidogrel. We conducted a retrospective cohort study of patients who were newly hospitalized for ACS between 1 January 2006 and 31 December 2007 retrieved from the Taiwan National Health Insurance Research Database (NHIRD) and who were prescribed clopidogrel (n= 37 099) during the follow-up period. A propensity score technique was used to establish a matched cohort in 1:1 ratio (n= 5173 for each group). The primary clinical outcome was rehospitalization for ACS, while secondary outcomes were rehospitalization for percutaneous transluminal coronary angioplasty (PTCA) with stent, PTCA without stent and revascularization (PTCA or coronary artery bypass graft surgery) after the discharge date for the index ACS event. The adjusted hazard ratio of rehospitalization for ACS was 1.052 (95% confidence interval, 0.971-1.139; P= 0.214) in the propensity score matched cohort. Among all PPIs, only omeprazole was found to be statistically significantly associated with an increased risk of rehospitalization for ACS (adjusted hazard ratio, 1.226; 95% confidence interval, 1.066-1.410; P= 0.004). Concomitant use of esomeprazole, pantoprazole, rabeprazole and lansoprazole did not increase the risk. Our study indicated no statistically significant increase in the risk of rehospitalization for ACS due to concurrent use of clopidogrel and PPIs overall. Among individual PPIs, only omeprazole was found to be statistically significantly associated with increased risk of rehospitalization for ACS.

Partial symptom‐response to proton pump inhibitors in patients with non‐erosive reflux disease or reflux oesophagitis – a post hoc analysis of 5796 patients

Although most patients with gastro-oesophageal reflux disease (GERD) benefit from proton pump inhibitor (PPI) therapy, some experience only partial symptom relief. To determine the prevalence of partial heartburn response to PPIs and its impact on health-related quality of life. Four randomised, double-blind studies in adults with reflux disease compared esomeprazole 40 mg/day or 20 mg/day with omeprazole 20 mg/day, or esomeprazole 40 mg/day with pantoprazole 40 mg/day. Patients with heartburn on ≥4 days during the 1-week recall period at baseline were included. Partial response was defined as heartburn on ≥3 days during the last treatment week and reduced heartburn frequency after 4 weeks of treatment compared with baseline. The analysis included 2645 patients with non-erosive reflux disease (mean age: 48.8 years; 54.4% women) and 3151 patients with reflux oesophagitis (mean age: 50.6 years; 37.1% women). At baseline, most patients reported heartburn on 5-7 days (non-erosive reflux disease: 82.2%; reflux oesophagitis: 86.8%). Partial heartburn response occurred in 19.9% of patients with non-erosive reflux disease and 14.0% with reflux oesophagitis. Defining partial response as heartburn on ≥2 days increased these rates to 26.2% and 19.3%, respectively; defining partial response as heartburn of moderate or severe intensity on ≥3 days decreased these rates to 6.4% and 5.3%, respectively. Nonresponse to PPIs was rare (non-erosive reflux disease: 2.4%; reflux oesophagitis: 1.4%). Using our conservative definition, partial heartburn response to proton pump inhibitor therapy occurred in 14-20% of gastro-oesophageal reflux disease patients, more commonly in non-erosive reflux disease than in reflux oesophagitis.

PTU-167 The role of proton pump inhibitors in patients with Barrett's oesophagus following laparoscopic fundoplication can only be determined after the level of residual reflux has been quantified

IntroductionLaparoscopic fundoplication is carried out for pathological Gastro Oesophageal Reflux in patients with and without Barrett's oesophagus. It has been suggested that in patients with Barrett's, only those patients with...

Predicting the efficacy of proton pump inhibitors in patients with non‐erosive reflux disease before therapy using dual‐channel 24‐h esophageal pH monitoring

We aimed to determine whether reflux- and symptom-related parameters can predict the efficacy of proton pump inhibitors (PPI) in non-erosive reflux disease (NERD). Twenty-seven NERD patients who had experienced heartburn more than once a week within the previous month were enrolled. Intraesophageal pH before therapy was measured simultaneously at 5 and 15 cm above the esophagogastric junction (EGJ) for 24 h. The PPI rabeprazole was administered at a dose of 10 mg once daily for 4 weeks. In the event that heartburn was not relieved, the dose was increased to 10 mg twice daily for an additional 2 weeks, and again to 20 mg twice daily for another 2 weeks. Univariate analysis demonstrated no significant associations between any reflux- or symptom-related parameters at either site and complete heartburn relief after 4 weeks, or cumulative complete heartburn relief after 8 weeks. However, post-hoc analysis demonstrated more satisfactory heartburn relief after 4 weeks in patients with a high symptom index compared with those with a low symptom index, at 5 cm above the EGJ (P = 0.009). Cumulative satisfactory heartburn relief after 8 weeks was also greater in patients with a high total number of acid reflux episodes compared with those with a low total number of episodes, at 15 cm above the EGJ (P = 0.037). Pre-therapeutic pH monitoring in the lower and mid-esophagus is useful for predicting the efficacy of PPI in NERD patients.

Adverse cardiovascular outcomes associated with concurrent use of clopidogrel or ticlopidine and proton-pump inhibitors in patients undergoing percutaneous coronary intervention

Recent clinical studies reported the drug interaction between proton-pump inhibitors (PPI) and clopidogrel, which remains controversial. The aim of this study was to determine whether the concurrent use of PPI with clopidogrel or ticlopidine is associated with increased risk for adverse cardiovascular outcomes in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). In this retrospective cohort study, we assessed the cardiovascular outcomes associated with the concurrent use of PPI and clopidogrel or ticlopidine in the well-characterized 1286 patients with CAD undergoing PCI in the University of Tokyo Hospital. In the Japanese patients with CAD undergoing PCI, the concurrent use of PPI was significantly associated with increased risk for major adverse cardiovascular events in the ticlopidine users (hazard ratio 2.63; 95 % confidence interval 1.65-4.18; P < 0.001), but not in the clopidogrel users. In the clopidogrel users as well as the ticlopidine users, PPI use did not affect the occurrence of target lesion revascularization, but significantly increased the risk for new lesion formation in the coronary arteries, which required subsequent revascularization. The adverse cardiovascular effects of the concurrent use of PPI and ticlopidine were identified in the patients with CAD undergoing PCI. Also, new lesion formation in the coronary arteries was shown to be increased when PPI was coprescribed for the thienopyridine users.

Effect of Proton Pump Inhibitor in Patients with Acute Pancreatitis - Pilot Study

Oxygen free radicals play an important role in acute pancreatitis. Pantoprazole as a proton pump inhibitor (PPI) has pancreatic anti-secretory effect and a pronounced inhibitory reactivity towards hydroxyl radicals. The objective of the study was to investigate the effect of pantoprazole on the course of acute pancreatitis. We conducted a prospective randomized trial involving 40 patients with acute pancreatitis. Patients were divided into two groups. One group received PPI and the other group did not receive PPI. In the PPI group, patients received pantoprazole 40 mg intravenously twice a day for fasting time, and then 40 mg orally twice a day until discharge. There were no significant differences in baseline characteristics and laboratory markers between two groups. In the pantoprazole group, mean hospital stay was 7.4 days, time to start oral intake was 69.0 hours, and time to pain relief was 59.7 hours. Acute physiology and chronic health evaluation (APACHE) II score was 3.15 at admission day and 2.35 at discharge. On the other hand, in the non-pantoprazole group, mean hospital stay was 7.6 days, time taken to start oral intake was 71.4 hours, and time taken to pain relief was 61.8 hours. APACHE II score was 4.4 at admission and 2.85 at discharge. However, there were no significant differences between two groups. Treatment with pantoprazole did not have influence on the clinical course of acute pancreatitis. But, considering it was a pilot study, large scale prospective trials will be needed.

Comparison of Daily Average Consumption Between Different Proton Pump Inhibitors in Patients with Gastroesophageal Reflux Disease

Purpose: Numerous randomized clinical trials have shown the benefits of proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease (GERD). Due to inadequate symptom control of once daily dosing, approximately 12-20% of patients use twice daily dosing of PPIs. The objective of this study was to compare daily average consumption (DACON) among GERD patients treated with different branded and generic PPIs. Methods: We conducted a retrospective database analysis using commercial enrollees from a large U.S. health plan from February 2008 to December 2009. Adult GERD patients with ≥1 medical claim with ICD-9 diagnosis codes 530.1, 530.10-530.12, 530.81, or 787.1, ≥1 PPI Rx claim during the identification period of February 2009 to September 2009, and continuous eligibility for 12 months before and 6 months after the index date were identified. The date of the first PPI Rx claim during the identification period was considered as the index date. DACON was defined as quantity of medication dispensed over the number of days with medication. We controlled for age, gender, region, GERD severity, plan type, pre-index Quan-Charlson comorbidity score (CCI), DACON, and costs and utilization. Results: Among 185,506 GERD patients identified, 2.3% were taking dexlansoprazole, 5.0% lansoprazole, 9.6% esomeprazole, 19.6% rabeprazole, 30.2% pantoprazole, and 33.3% omeprazole at the index date. Over half of the patients (56.47%) were branded PPI users and 43.53% (n=80,749) were generic PPI users at the index date. Patients in the branded PPI group were more likely to be younger (51.32 vs. 52.25 years, p<0.001), female (57.00% vs. 55.36%, p<0.001), reside in the southern part of the United States (57.65% vs. 48.00%, p<0.001), use point-of-service (56.54% vs. 53.06%, p<0.001) and exclusive provider organization (15.32% vs. 12.92%, p<0.001) health plans and had lower CCI (0.81 vs. 0.90, p<0.001) compared to patients in the generic PPI group. The highest DACON was among omeprazole users (1.32), followed by users of lansoprazole (1.20), rabeprazole (1.18), pantoprazole (1.16), esomeprazole (1.15) and dexlansoprazole (1.04). After risk adjustment, branded PPI users had a lower DACON (1.09 vs. 1.28, p<0.001) compared to generic PPI users. Conclusion: There were differences in DACON values between the different PPIs with dexlansoprazole showing the lowest and omeprazole showing the highest DACON. Branded PPI users showed lower DACON compared to generic PPI. The potential impact of reduced DACON on patient adherence, length of treatment and total and GERD-related healthcare resource utilization and costs requires further evaluation. Disclosure: Dr Mody - Employee: Takeda Pharmaceuticals International, Inc. All other authors were contracted research vendors for this study for Takeda Pharmaceuticals international, Inc. This research was supported by an industry grant from Takeda Pharmaceuticals International, Inc. funded this project.

Safety of clopidogrel and proton pump inhibitors in patients undergoing drug-eluting stent implantation

A pharmacodynamic interaction between clopidogrel and proton pump inhibitors (PPIs) has been suggested, leading to reduced clopidogrel-induced platelet inhibitory effects. However, data from clinical studies are conflicting. The aim of this study was to evaluate the safety of long-term clopidogrel and PPI therapy. A total of 1328 consecutive patients (age 63±11 years; 81% male) undergoing drug-eluting stent implantation and 1-year follow-up were included. All patients were treated with a standard aspirin and clopidogrel treatment regimen for 12 months. The concomitant PPI therapy for the same duration was at the discretion of the clinical cardiologist. PPI therapy included lansoprazole (30 mg/day), pantoprazole (20 mg/day), or omeprazole (20 mg/day). At 1-year follow-up, major adverse cardiac events (MACE), defined as death, myocardial infarction (MI), acute coronary syndrome leading to hospitalization and nonfatal stroke, were recorded. All cause death, any stent thrombosis (ST), and bleeding (Thrombolysis in MI major and minor) were also assessed. Lansoprazole, pantoprazole, and omeprazole were administered to 855, 178, and 125 patients, whereas 170 were not prescribed any PPI therapy. Among patients treated with PPIs, those on pantoprazole had more often prior MI, multivessel coronary artery disease, and chronic kidney disease, whereas earlier peptic ulcer was more frequent among patients treated with omeprazole. The incidence of 1-year MACE was not statistically different between patients in the PPI and no-PPI groups (7.5 vs. 5.0%; P=0.26). Similarly, 1-year rates of all cause death, ST, and Thrombolysis in MI major and minor bleedings did not significantly differ. After statistical adjustment for potential confounders, the concomitant use of clopidogrel and PPIs was not associated with the risk of 1-year MACE [odds ratio (OR) 1.54, P=0.38], death (OR: 0.97, P=0.961), and ST (OR: 1.01, P=0.998). No differences across the three PPI types were found. The association of clopidogrel and PPIs after drug-eluting stent implantation, prescribed on clinical judgement, seems safe.

Partial Symptom Response to Proton Pump Inhibitors in Patients With Non-Erosive Reflux Disease and Reflux Esophagitis

Partial Symptom Response to Proton Pump Inhibitors in Patients With Non-Erosive Reflux Disease and Reflux Esophagitis

Abnormal Pharyngeal pH Testing Predicts Response to Proton Pump Inhibitors in Patients with Chronic Cough and Laryngeal Complaints

RATIONALE: Controversy exists as to the role of extra-esophageal reflux in the pathogenesis of chronic cough and laryngopharyngitis. One reason for this lack of consensus is the absence of a reliable diagnostic modality capable of determining which patients are likely to respond to anti-reflux measures. We sought to determine whether abnormal pharyngeal pH testing with the DxpH Measurement System is helpful for predicting which patients presenting with chronic cough and/or laryngeal complaints are likely to respond to acid suppression therapy. METHODS: Nineteen consecutive subjects presenting to an allergy department with cough and/or additional symptoms suspected to be of laryngeal origin and with abnormal pharyngeal pH testing were surveyed regarding symptom response and adherence to treatment with twice daily proton pump inhibitors. Self-reported symptom improvement scores from subjects reporting adherence to acid suppression therapy were compared to those of subjects reporting incomplete adherence to acid suppression therapy. RESULTS: The presenting symptoms included chronic cough, sensation of excessive throat mucus / post-nasal drip, throat clearing, globus, and hoarseness. Of those subjects with abnormal pharyngeal pH studies who took twice daily proton pump inhibitors as directed, 11 of 14 (78.6%) had >50% improvement in symptoms as compared to 1 of 5 subjects (20%) with abnormal pH studies who did not (P = 0.04). CONCLUSIONS: Pharyngeal pH testing with the DxpH Measurement System in patients presenting with symptoms of chronic cough and/or laryngopharyngitis is helpful in predicting response to acid suppression therapy.

Effects of Proton Pump Inhibitors in Patients Receiving Clopidogrel

With great interest we read the results of a meta-analysis by Kwok et al. about the effects of proton pump inhibitors (PPIs) on adverse gastrointestinal events in patients receiving clopidogrel. The authors analysed the published literature in a field that has received much attention recently, mainly because of a suggested interaction between clopidogrel and PPIs. Of interest, the authors also published some months ago a meta-analysis on the cardiovascular outcomes of the combined use of clopidogrel and PPIs. Based on both their publications, we would like to make two comments on (i) the heterogeneity of included studies; and (ii) the practical advice to physicians regarding the issue of potential interaction in clinical practice. Kwok et al. identified ten relevant studies that can be characterized by much heterogeneity in the results and also in study design, population, and outcomes. For example, only one study was a randomized clinical trial, two were retrospective cross-sectional studies, two were casecontrol studies and five were retrospective cohort studies. In their study, the authors acknowledged that heterogeneity in outcome definitions was present and they therefore performed subgroup analyses on separate outcomes. However, we question whether these studies can be pooled at all because of the variations as mentioned above. Second, the results of both meta-analyses were used to convince both physicians and patients that the combined use of clopidogrel and PPIs is indeed not harmful. They stated that there are no clear differences in cardiovascular outcomes between clopidogrel users with or without a PPI, and that PPIs are associated with a reduction in gastrointestinal bleeding. However, these are all relative risks and mostly based on studies that performed many statistical adjustments. It is important to stress that physicians and patients face absolute risks in clinical practice instead of relative risks. In a recent publication by our group, which was not included by Kwok et al., we concluded that although there seems to be no clinical interaction, patients using the combination of clopidogrel and a PPI have a 2-fold increased unadjusted risk for cardiovascular outcomes, and even a 5-fold increased unadjusted risk for gastrointestinal outcomes. In conclusion, physicians should interpret the results of these meta-analyses with caution because it can be disputed whether these studies can be pooled. Based on our results, we conclude that patients using the combination of clopidogrel and a PPI are at an increased (absolute) risk of cardiovascular and gastrointestinal adverse outcomes. This is probably not due to the combined use of these medications but to the fact these patients have an inferior cardiovascular and gastrointestinal risk profile and the occurrence of channelling bias in the published studies.

Cardiovascular and gastrointestinal events of three antiplatelet therapies: clopidogrel, clopidogrel plus proton-pump inhibitors, and aspirin plus proton-pump inhibitors in patients with previous gastrointestinal bleeding

Concomitant use of antiplatelet agents and proton-pump inhibitors (PPIs) has been recommended in patients with a history of gastrointestinal (GI) hemorrhage. However, recent studies have reported that PPIs may alter clopidogrel's pharmacokinetics and potentially lead to an increased risk of recurrent adverse cardiovascular (CV) events. Using Taiwan's 2000-2006 National Health Insurance database, this population-based retrospective cohort study assessed CV and GI events in patients who had a prior history of GI bleeding and had been prescribed ongoing antiplatelet therapy after acute coronary syndrome (ACS) discharge. We identified 3,580 ACS patients and categorized them into (1) those taking clopidogrel alone, (2) those taking clopidogrel plus PPIs, and (3) those taking aspirin plus PPIs. Cox proportional hazards models were used to assess the association between the use of antiplatelet therapies and CV/GI events. The clopidogrel only group and the clopidogrel plus PPI group were found to be at lower risk for GI events than the aspirin plus PPI group [adjusted hazard ratio (HR) 0.23 (95% confidence interval; CI 0.14-0.36) and HR 0.70 (0.52-0.96), respectively]. However, while the clopidogrel only group had a lower risk of CV events than the aspirin plus PPI group [HR 0.57 (0.38-0.84)], the clopidogrel plus PPI group had a significantly higher CV risk than the aspirin plus PPI group [HR 1.59 (1.18-2.13)]. Our findings suggest that although the use of clopidogrel plus PPIs provides GI benefits, with this treatment, there is an increased CV risk among patients with a history of GI bleeding.

This Month in Gastroenterology

This Month in Gastroenterology

Helicobacter pylori infection and Nonmalignant Diseases

Several interesting studies have been published on nonmalignant Helicobacter pylori-related conditions over the past year, which are reviewed in this article. A revival of interest in the histologic classification of gastritis has led to grading of gastritis into stages correlating with risk of neoplastic progression, new data to improve this concept have been published. Unselected prescription of proton-pump inhibitors in patients with dyspepsia has been questioned by the finding that withdrawal of proton-pump inhibitors induces acid-related symptoms in healthy volunteers, probably by the mechanism of rebound gastric acid hypersecretion. Additional data on the rationale of tapering proton-pump inhibitor therapy are therefore awaited. Moreover, new data on peptic ulcer disease and its complications provide clear recommendations for daily clinical practice. Testing and eradication of H.pylori in patients with peptic ulcer bleeding is essential. However, in H.pylori-negative peptic ulcer disease, high overall patient mortality should be acknowledged, and this should guide considering continuation of nonsteroidal anti-inflammatory drugs. The role of H.pylori in the pathogenesis of gastroesophageal reflux disease is still unclear. An association has been described by several studies; however, it cannot be translated to individual risks for development of gastroesophageal reflux disease after H.pylori eradication. Possibly, additional data on subgroups, such as gastric ulcer, duodenal ulcer patients, and associated gastric mucosal changes, will solve this issue.

Update in Gastroenterology and Hepatology

Updates6 July 2010Update in Gastroenterology and HepatologyNorton J. Greenberger, MD and Prateek Sharma, MDNorton J. Greenberger, MDFrom Kansas University School of Medicine, Kansas City, Kansas, and Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts.Search for more papers by this author and Prateek Sharma, MDFrom Kansas University School of Medicine, Kansas City, Kansas, and Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-153-1-201007060-00245 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail This year's update in gastroenterology and hepatology reviews a range of important findings published in 2009, including a comparison of medical and surgical treatments for gastroesophageal reflux disease, radiofrequency ablation of Barrett esophagus, and gastroesophageal reflux disease in asthma. The controversial subject of the concurrent use of proton-pump inhibitors in patients receiving antiplatelet therapy, such as clopidogrel, is reviewed. A new and important scoring system for predicting mortality in acute pancreatitis is presented. The widespread and often unrecognized problem of pelvic floor disorders in women is discussed in detail. Bile salt malabsorption, an important cause of diarrhea-predominant irritable bowel syndrome, ...Reference1. Zocco MA, Di Stasio E, De Cristofaro R, Novi M, Ainora ME, Ponziani F, et al. Thrombotic risk factors in patients with liver cirrhosis: correlation with MELD scoring system and portal vein thrombosis development. J Hepatol. 2009;51:682-9. [PMID: 19464747] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Kansas University School of Medicine, Kansas City, Kansas, and Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts.Article relevant to primary care general internistsArticle relevant to hospitalistsDisclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M10-0270.Corresponding Author: Norton J. Greenberger, MD, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115; e-mail, [email protected]org.Current Author Addresses: Dr. Greenberger: Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115.Dr. Sharma: Mailstop 1023, 3901 Rainbow Boulevard, Kansas City, KS 66160. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 6 July 2010Volume 153, Issue 1Page: 34-39KeywordsAcute pancreatitisAsthmaBileCirrhosisDysplasiaEsophagusGastroesophageal reflux diseaseIncontinence ePublished: 6 July 2010 Issue Published: 6 July 2010 Copyright & PermissionsCopyright © 2010 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...

Histamine 2-Receptor Antagonists Are an Alternative to Proton Pump Inhibitor in Patients Receiving Clopidogrel

Previous observational studies reported that concomitant use of clopidogrel and proton pump inhibitors (PPIs) in patients with prior acute coronary syndrome (ACS) was associated with adverse cardiovascular outcomes. We investigated whether H(2)-receptor antagonist (H(2)RA) is an alternative to PPI in patients with ACS. We conducted a population-based retrospective cohort study of 6552 patients in Taiwan discharged for ACS between 2002 and 2005. Patients were divided into 5 cohorts: clopidogrel plus H(2)RA (n = 252), clopidogrel plus PPI (n = 311), clopidogrel alone (n = 5551), H(2)RA alone (n = 235), and PPI alone (n = 203). The primary outcome was rehospitalization for ACS or all-cause mortality within 3 month of rehospitalization. The 1-year cumulative incidence of the primary outcome was 26.8% (95% CI: 21.5%-33.0%) in the clopidogrel plus H(2)RA cohort and 33.2% (95% CI: 27.8%-39.4%) in the clopidogrel plus PPI cohort, compared with 11.6% (95% CI: 10.8%-12.5%) in the clopidogrel alone cohort (P < .0001). No significant difference was observed between the PPI alone cohort (11.0%; 95% CI: 7.1%-16.8%), the H(2)RA alone cohort (11.8%; 95% CI: 8.2%-16.8%), and the clopidogrel alone cohort in terms of the primary outcome. The number needed to harm was 7 with concomitant H(2)RA and 5 with concomitant PPI. On multivariate analysis, concomitant H(2)RA and PPI were independent risk factors predicting adverse outcomes (adjusted hazard ratios, 2.48 and 3.20, respectively; P < .0001). Concomitant use of clopidogrel and H(2)RA or PPI after hospital discharge for ACS is associated with increased risk of adverse outcomes.