Use Of Proton Pump Inhibitors In Patients Research Articles

#2824 Use of proton pump inhibitors is not associated with post-dialysis fatigue and time of recovery after dialysis in patients on chronic hemodialysis

Abstract Background and Aims Chronic hemodialysis is often associated with post-dialysis fatigue (PDF), a condition characterized by extreme tiredness and lack of energy. PDF is a debilitating symptom that significantly impairs quality of life of hemodialysis patients. Furthermore, PDF is independently associated with the time to recover after dialysis (TIRD), which can be used as an indirect measure of PDF. Recent studies have shown that the use of proton pump inhibitors (PPI) is independently associated with the prevalence and severity of fatigue in kidney transplant recipients. The aim of this study is to determine whether the use of PPIs in patients undergoing chronic hemodialysis is associated with PDF prevalence and characteristics, as well as the TIRD. Method For this retrospective study, we recruited patients undergoing chronic hemodialysis and asked open-ended questions about their post-dialysis fatigue and time of recovery. Each patient was asked to rate the intensity, duration and frequency of their PDF on a scale of 1 to 5. We defined whether patients used a PPI (no PPI use or PPI use), the type of PPI used, the dose of PPI used, and the duration of the PPI use (<1 year or ≥1year). Results The study analysed 346 patients, of whom 259 used PPIs (55 used omeprazole, 63 esomeprazole, 54 pantoprazole, 87 lansoprazole, and 7 rabeprazole) and 87 did not. Among the patients, 232 reported suffering from PDF, while 114 did not. The median [min-max] TIRD was 210 minutes [0-1440]. The prevalence of PDF in PPI users and non-users was 67% and 68%, respectively (p= 0.878). There was no significant difference in the median [min-max] TIRD between PPI users and non-users (180 [0-1440] and 240 [0-1440], respectively; p=0.871). Additionally, there was no significant difference in the median PDF intensity, duration, frequency, and severity PPI users and non-users. The prevalence of PDF was similar among the different types of PPI used and did not differ with respect to PPI non-users. Duration of PPI exposure was <1 year in 42 patients and ≥1 year in 224 patients. There was no difference in prevalence of PDF between the two exposures. The correlation matrix showed no statistical significance between PPI equivalent dose, treatment duration, PDF frequency, PDF characteristics, and TIRD. Conclusion There is no association between the use of PPIs and PDF or time of recovery after dialysis in patients on chronic hemodialysis.

Association between proton pump inhibitors and risk of hepatic encephalopathy in patients undergoing transjugular intrahepatic portosystemic shunt: a protocol for a systematic review and meta-analysis

IntroductionHepatic encephalopathy (HE) is a major complication of acute liver failure, cirrhosis and transjugular intrahepatic portosystemic shunt (TIPS) placement. Its clinical manifestations range from mild cognitive deficits to coma. Furthermore,...

A Multinational Survey Investigating the Unmet Needs and Patient Perspectives Concerning Proton Pump Inhibitors in Systemic Sclerosis.

Proton pump inhibitors (PPIs) are widely prescribed to treat gastroesophageal reflux disease (GERD) in Systemic Sclerosis (SSc). However, not all patients adequately respond to the treatment, and there are frequent concerns about the safety of long-term use of PPIs. Our aim was to identify the main problems/complaints of SSc patients on PPIs, as well as understand their unmet needs. SSc patients treated with PPIs were invited through international patient associations and social media to participate in an online survey. We gathered 301 valid responses from 14 countries (United Kingdom 19.3% and United States 70.4%). Multiple PPIs use (two: 30% and three: 21% in series) was common. The majority (89%) reported improvement in gastrointestinal symptoms from receiving PPIs. Side effects attributed to receiving PPIs were uncommon (19%); however, most (79%) were potentially concerned. Around half (58%) had received lifestyle information, and most (85%) had searched online for information about PPIs. Only in the minority (12%) had a surgical approach been discussed; however, half (46%) indicated that they would be willing to undergo surgery to resolve their GERD symptoms but had important concerns. Despite the frequent use of PPIs in patients with SSc, there is significant heterogeneity in prescription, and combination therapy (PPIs plus other medication for acid reflux) is not uncommon (approximately 40%). Patients have significant concerns about PPIs side effects. Education about PPIs is often neglected, and patients very frequently use online sources to obtain information on drug treatment. A surgical approach is infrequently discussed, and patients fear this potential therapeutic approach.

Hepatic encephalopathy with proton pump inhibitor use in post tips patients: a systematic review and meta-analysis.

Hepatic encephalopathy (HE) after Trans-jugular intrahepatic portosystemic shunt (TIPS) is a common clinical problem. According to recent studies, Proton pump inhibitor (PPI) use can serve as an independent risk factor for HE. We performed a systematic review and meta-analysis to analyze the association between HE with PPI use versus without PPI use in patients undergoing TIPS. We conducted a comprehensive literature search from inception through February 15th, 2022 on MEDLINE, EMBASE, Cochrane Register of Controlled Trials, and Web of Science databases. Odds ratio (OR) was calculated when comparing dichotomous variables of patients with HE vs no HE in PPI use versus no PPI use in post TIPS patients. A 95% confidence interval (CI) and P values (<0.05 considered significant) were also generated. The search strategy yielded a total of 27 articles. We finalized four studies with a total of 825 patients. There was statistically significant difference in TIPS patients with HE in PPI users versus non-PPI users (OR 3.39 [1.79-6.43], P<0.01, I2=55.5%). Pooled mean average days to hospitalization was 215.2 days to hospitalization for hepatic encephalopathy in non-PPI users compared to 139.5 days in PPI users. Our study determines that there is a higher risk of post-TIPS HE in patients on PPI therapy vs. patients not receiving PPI therapy. We recommend using PPIs at a lower tolerable dose where necessary. Larger studies are needed to draw stronger conclusions.

Proton Pump Inhibitors For HIV+ Patients - A Word Of Caution.

Madam, HIV (human immunodeficiency virus) is on the rise in Pakistan. A Lancet global health modeling study reports that patient registration with the National Aids Control Program (NACP) has risen from 4500 in 2013 to 24331 in 2019 [1]. In HIV+ patients, the gastrointestinal tract is a common site of infection, often leading to anorexia, dysphagia, vomiting, weight loss, and diarrhoea. A study conducted in 2016 showed that 80% of HIV-infected adults had moderate-severe GERD (gastro-oesophageal reflux disorder) symptoms [2]. Physicians often prescribe proton pump inhibitors (PPIs) to treat GERD and stomach or duodenal ulcers. This class of drugs is the most potent inhibitor of gastric acid secretion and is ,unfortunately, prescribed excessively and often inappropriately, regardless of if the patient is HIV+. A recent study shows that 66.2% of patients in a tertiary care hospital in Karachi, Pakistan receive PPIs without proper indication [3]. However, PPIs being prescribed inappropriately pose severe health risks to individuals that are HIV+. A recent study in 2019 raised the valid concern that the use of PPIs in patients already receiving anti-retroviral (ARV) therapy in HIV+ patients could very well be related to an increased risk of acute kidney infection (AKI) [4]. This is not the only research to show the adverse effect of PPI use in HIV patients. A 2017 study shows statistically significant increased innate immune activation due to the translocation of microbial products in HIV+ patients taking PPIs [5]. This can carry serious future implications for these patients post-treatment because higher levels of innate immune activation markers are associated with immunological failure in HIV-treated patients [6]. These statistics raise a very critical question- is it safe for PPIs to be prescribed so freely without any attention to patients being HIV+ or on ARV therapy? It is suggested that existing and future ARV therapies be planned carefully if PPIs are prescribed, and close attention be paid to a patient’s virologic response. In the case of acute hospital admission, where PPIs are prescribed for preventing stress-induced or GI ulcers, medication reconciliation algorithms that acknowledge the interaction between protease inhibitors (PIs) and PPIs should be used [7]. It would be prudent to use PPIs strictly when prescribed and for lesser periods of time.

Increased mortality in patients with hematologic malignancies treated with proton pump inhibitors: a nationwide cohort study

Proton Pump inhibitors (PPIs) are frequently prescribed to cancer patients to prevent gastric mucosal damage. Post-diagnostic PPI use in patients with solid tumors may be associated with increased cancer mortality. However, the hazardous impact of PPIs in patients with hematologic malignancies remains unknown. This association was investigated in a large, retrospective cohort study using data from the Danish nationwide health registries. The outcomes were cancer-specific or non-cancer deaths. We identified 15,320 patients with hematologic malignancies and of these 1811 were identified as post-diagnostic PPI users. PPI users had significantly increased HRs for cancer-specific mortality (HR 1.31; 95% CI, 1.18–1.44) and 1-year cancer-specific mortality (HR 1.50, 95% CI 1.29–1.74) as compared to nonusers. The association between PPI use and increased cancer-specific mortality in Danish patients with hematologic malignancies supports the raised concerns regarding the frequent use of PPIs in cancer patients.

Executive Summary: Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU: Neurology, Peri-Transplant Medicine, Infectious Disease, and Gastroenterology Considerations.

Executive Summary: Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU: Neurology, Peri-Transplant Medicine, Infectious Disease, and Gastroenterology Considerations.

Effectiveness of Proton Pump Inhibitor Therapy in the Prevention of Bleeding After Prophylactic Endoscopic Variceal Band Ligation.

Background Endoscopic variceal ligation (EVL) is a surgical intervention that can work well to curb variceal bleeding in people with liver cirrhosis. However, it could make ulcer bleeding worse and be fatal in some cases. The widespread use of proton pump inhibitors (PPI) in cirrhotic individuals with variceal bleeding is empirical rather than based on scientific data. According to many studies, PPIs reduce the size of post-EVL ulcers. This study aimed to see if PPI use could reduce rebleeding after endoscopy therapy in cirrhotic patients with variceal bleeding. Methodology A retrospective cross-sectional study was conducted at a tertiary care hospital from August 2019 to September 2021. Cirrhotic patients with bleeding gastroesophageal varices(GEVs) who had undergone EVL at the same hospital were enrolled in the study. Medical records were organized, and the sample was divided into two groups based on whether or not PPI was given. Both PPI and non-PPI patients had their endoscopic findings, initial hemostasis outcomes, rebleeding rates, bleeding-related mortality rates, and treatment-related comorbidities compared. Results A total of 46 patients were selected for the study and divided into two groups (PPI group n=28 and non-PPI group n=18). The majority of the patients were males. The PPI group had a mean age of 58.6 ±7.8 years, whereas the non-PPI group had a mean age of 53.6 ±4.4 years. Hepatitis B virus (HBV) infection was the most prevalent cause of cirrhosis in both groups. After endoscopic treatment, three patients (16%) in the non-PPI group suffered a variceal hemorrhage. Bleeding-related fatalities and the time it took for the bleeding to stop varied significantly between the two groups. History of variceal bleeding (relative risk (RR)=1.45; 95% confidence interval (CI), 1.60-7.67; p=0.02), presence of gastric varices (RR=2.23; 95% CI, 2.56-9.832; p=0.035), and not administering PPIs (RR =7.542; 95% CI, 3.98-29.13; p=0.008) were linked with rebleeding. The presence of red concurrent esophageal varices (RR=6.37; 95% CI, 0.562-15.342; p=0.002) and failure to provide PPIs (RR=2.3; 95% CI, 1.621-25.64; p=0.04) were linked with post-EVL bleeding in a multivariate analysis. Conclusions Proton pump inhibitors reducethe occurrence of early bleeding and adverse events after EVL in cirrhotic patients. Not prescribing PPIs and the presence of GEVs were substantially related to a higher risk of bleeding during preventative EVL. Not initiating PPI medication immediately was the sole predictor of bleeding complications in patients who had undergone EVL without gastric varix treatment. To lower the risk of post-EVL ulcer bleeding, we recommend PPI use in patients undergoing EVL.

Efficacy and Safety of Concomitant Proton Pump Inhibitor and Nivolumab in Renal Cell Carcinoma: Results of the GETUG-AFU 26 NIVOREN Multicenter Phase II Study

Proton pump inhibitors (PPI) may influence the gut microbiome and thus impact the effectiveness of immune checkpoint inhibitors (ICI). The effect of PPIs on the outcomes of ICI has not been fully explored and investigated in metastatic renal cell carcinoma (mRCC). This retrospective analysis used prospectively collected data from the GETUG-AFU 26 NIVOREN (NCT03013335) phase II study which enrolled 729 mRCC patients of whom 720 were treated with nivolumab. The main objective of this analysis was to evaluate the impact of PPI on the efficacy and safety outcomes of mRCC patients. PPI use was defined as PPI administration on the day of ICI initiation. Of the 707 patients with mRCC analyzed in this study, 196 (27.7%) were PPI users. The majority of PPI users were males (80.6%), had an ECOG performance status of 0-1 (78.9%) and a nephrectomy (82.1%). Almost two-thirds of the patients had a favorable and intermediate IMDC risk category and 52% received nivolumab in the third line and beyond. PPI use did not correlate with PFS or OS (HR=0.89, 95% CI 0.74-1.08 and HR=1.24; 95% CI, 0.98-1.58, respectively). Grade 3-5 nivolumab-related adverse events were more common among PPI users (25.5% vs. 15.3%). This real-world study suggests that PPI use in patients with mRCC does not impact the efficacy outcomes but may influence the safety of nivolumab which warrants further investigations.

Proton Pump Inhibitors Use and Increased Risk of Spontaneous Bacterial Peritonitis in Cirrhotic Patients: A Retrospective Cohort Analysis.

BackgroundSince their introduction in the early 1980s, proton pump inhibitors (PPIs) have been used worldwide for a broad range of indications. Unfortunately, however, PPIs have become overly prescribed by healthcare providers, sometimes in the absence of clear indications. Although PPIs were initially presumed to have an excellent safety profile, emerging studies have shed light on the association between their long-term use and a myriad of side effects, including the possibility of an increased risk of spontaneous bacterial peritonitis (SBP). Data available to date regarding the association between PPI use and SBP development in cirrhotic patients is conflicting. While some observational studies provide no association between PPI use in cirrhotic patients and an increased risk of SBP development, many others support this association. As a result of the conflicting conclusions from case controls, cohorts, and meta-analyses, we aimed to carry out this retrospective cohort analysis of data from cirrhotic patients included in the electronic medical record-based commercial database, EXPLORYS (IMB-WATSON, Cleveland, Ohio). Our aim was to evaluate for a possible association between PPIs use and the risk of SBP development in cirrhotic patients and to compare the prevalence of SBP development between cirrhotic patients who were actively using PPIs and those who were not.MethodsA retrospective cohort analysis with chart review was conducted on patients with cirrhosis who were included in the electronic medical record-based commercial database, EXPLORYS (IMB-WATSON, Cleveland, Ohio). Using this database, records were reviewed between December 2017 and 2020. Included patients were adults aged 30 to 79 years with a Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT) diagnosis of liver cirrhosis. Included patients with a SNOMED-CT diagnosis of liver cirrhosis were divided into two groups: the first group included all cirrhotic patients who did not use PPIs and the second group included all cirrhotic patients who were on PPIs at home.ResultsIn our analysis, SBP occurred in 1.7% (1,860 patients) of the included cirrhotic patients whether they were actively taking PPIs or not. Among the 40,670 cirrhotic patients who were on PPIs at home, 1,350 (3.3%) patients developed SBP. On multivariate analysis, PPI use was the strongest predictor for SBP in cirrhotic patients (odds ratio (OR) = 4.24; 95% confidence interval (CI): 3.83 - 4.7, P value < 0.0001), with cirrhotic patients taking PPIs being 4.24 more likely to develop SBP than those not on PPIs. In addition, PPI use, history of bleeding varices, age, race, and gender were found to be independent predicting factors for SBP, in descending order of importance.ConclusionsOur retrospective cohort analysis has shown that the use of PPIs in patients with liver cirrhosis is an independent predicting risk factor for SBP development. It solidified the argument that cirrhotic patients receiving this form of therapy seem to have a higher risk of developing SBP. In the setting of the emerging evidence that PPIs might impose health risks in cirrhotic patients, further studies are needed to settle the current debate between supporters and opponents of this proposition. In addition, future studies may help clarify the relationship between the occurrence of SBP in cirrhotic patients and the type, dose, and duration of PPIs used. We recommend that unless it is clearly indicated, PPI therapy should be avoided or administered with caution in patients with cirrhosis.

Association of proton pump inhibitor use with survival outcomes in patients with cancer treated with immune checkpoint inhibitors: A systematic review and meta-analysis.

2613 Background: Proton pump inhibitors (PPIs) were revealed to regulate gut microbiome alterations and further impact the response to immune checkpoint inhibitors (ICIs). Contradictory impacts on survival were observed in ICI-treated patients when concomitantly use PPI or not. We performed this systematic review and meta-analysis to analyze the association of PPI use with survival outcomes in ICI-treated cancer patients. Methods: EMBASE, MEDLINE/PubMed, Cochrane Library databases and major oncology conferences proceedings were comprehensively searched. Studies comparing overall survival (OS) and progression-free survival (PFS) between PPI use and PPI non-use in ICI-treated cancer patients were included. Data regarding the characteristics, ICI and PPI treatments and survival outcomes for patients were extracted. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using random-effect models. Subgroup meta-analyses and meta-regressions were performed to explore possible factors of heterogeneity among study results. Results: A total of 20 studies were included, comprising 2812 ICI- and PPI-treated patients and 3990 ICI-treated and PPI-free patients. The pooled HR is 1.30 (95% CI, 1.17-1.45; P &lt;.001) for OS and 1.20 (95% CI, 1.08-1.34; P &lt;.001) for PFS, indicating a significant negative association between PPI use and survival of ICI-treated patients. Subgroup meta-analyses by factors including cancer types, ICI types and time window of PPI use, revealed such associations were in patients with non-small cell lung cancer (OS: HR = 1.40, 95% CI = 1.23 to 1.59, P &lt;.001; PFS: HR = 1.27, 95% CI = 1.16 to 1.40, P &lt;.001) or urothelial cancer (OS: HR = 1.50, 95% CI = 1.26 to 1.80, P &lt;.001; PFS: HR = 1.37, 95% CI = 1.17 to 1.60, P &lt;.001), patients treated with anti-PD-1/PD-L1 (OS: HR = 1.41, 95% CI = 1.30 to 1.53, P &lt;.001; PFS: HR = 1.29, 95% CI = 1.20 to 1.38, P &lt;.001), patients receiving PPI as baseline treatment (OS: HR = 1.43, 95% CI = 1.21 to 1.69, P &lt;.001; PFS: HR = 1.29, 95% CI = 1.16 to 1.44, P &lt;.001) or 60 days before ICI treatment initiation (OS: HR = 1.28, 95% CI = 1.11 to 1.48, P &lt;.001; PFS: HR = 1.27, 95% CI = 1.16 to 1.40, P &lt;.001), rather than concomitantly with ICI initiation. Conclusions: PPIs use in patients treated with ICIs is associated with a shorter OS and PFS, especially in several specific subgroups of cancer patients. PPIs should be strictly controlled, and appear to not impact survival if given temporarily after ICIs initiation. These detailed observations could provide basis for clinical guidelines when concomitantly use PPIs and ICIs.

Proton Pump Inhibitors and In-Hospital Gastrointestinal Bleeding in Patients With Acute Coronary Syndrome Receiving Dual Antiplatelet Therapy

ObjectiveTo evaluate the association between proton pump inhibitor (PPI) use and in-hospital gastrointestinal (GI) bleeding in patients with acute coronary syndrome (ACS) taking dual antiplatelet therapy (DAPT). Patients and MethodsThis study is based on the Improving Care for Cardiovascular Disease in China-ACS project, an ongoing collaborative registry and quality improvement project of the American Heart Association and the Chinese Society of Cardiology. A total of 25,567 patients with ACS taking DAPT from 172 hospitals from July 1, 2017, through December 31, 2018, were included. Multivariable Cox regression and propensity score–matched analyses were used to evaluate the association between PPI use and in-hospital GI bleeding. ResultsOf these patients with ACS, 63.9% (n=16,332) were prescribed PPIs within 24 hours of admission. Patients using PPIs had a higher rate of GI bleeding compared with those not using PPIs (1.0% vs 0.5%; P<.001). In the multivariable Cox regression analysis, early PPI use was associated with a 58% higher risk of GI bleeding (hazard ratio, 1.58; 95% CI, 1.15 to 2.18; P=.005). Further propensity score matching attenuated the association but still showed that patients using PPIs had a higher rate of GI bleeding (0.8% vs 0.6%; P=.04). ConclusionIn China, PPIs are widely used within 24 hours of admission in patients with ACS taking DAPT. An increased risk of GI bleeding is observed in inpatients with early PPI use. Randomized trials on early use of PPIs in patients with ACS receiving DAPT are warranted. Trial Registrationclinicaltrials.gov Identifier: NCT02306616.

Correlation Between Proton Pump Inhibitors and the Complications of Liver Cirrhosis: A Systematic Review and Meta-Analysis.

Many studies and meta-analyses have investigated the associations among proton pump inhibitors (PPIs), spontaneous bacterial peritonitis (SBP), portosystemic encephalopathy (PSE), and other infections. However, these studies had limitations, including the omission of several relevant studies and drawing conclusions, based on the abstracts without consulting the full-text of the articles. To evaluate the association between PPIs and complications arising from cirrhosis and risks of PPI use in patients with cirrhosis. Data were extracted from the EMBASE, PubMed, Cochrane, and Google Scholar databases. The Newcastle-Ottawa scale was used to assess the quality of the selected studies. A total of 29 studies (13 case-control and 16 cohort studies) involving 20,484 patients were included in the meta-analysis. The total relative risk (RR) for the 23 studies which investigated SBP was 1.31, and the 95% CI was 1.10-1.55 (I2 = 73.0%). The total RR for the 7 studies which examined PSE was 1.25 (95% CI 0.85-1.84, I2 = 96.1%). For the 7 studies which analyzed overall infection, the total RR was 1.37 (95% CI 1.07-1.76, I2 = 79.3%). The RR for the 2 cohort studies that assessed mortality was 1.39 (95% CI 0.85-2.27, I2 = 0.0%). PPI use in cirrhosis patients increased the SBP and overall infection risk. PPIs should be considered with appropriate indications when the benefits exceed the risks in cirrhosis patients with ascites.

Association of proton pump inhibitor use with survival outcomes in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis.

Background:Proton pump inhibitors (PPIs) have been shown to regulate the gut microbiome and affect the response to immune checkpoint inhibitors (ICIs). Contradictory results on survival have been observed in patients concomitantly treated with ICIs and PPIs. We performed a systematic review and meta-analysis to determine the association between PPI use and survival outcomes in ICI-treated cancer patients.Methods:EMBASE, MEDLINE/PubMed, Cochrane Library databases, and major oncology conference proceedings were searched. Studies comparing overall survival (OS) and progression-free survival (PFS) between PPI-treated and PPI-free groups of ICI-treated cancer patients were included. Data regarding study and patient characteristics, ICI and PPI treatments, and survival outcomes were extracted. Hazard ratios (HRs) with 95% confidence interval (CI) were pooled using random effects models. Subgroup meta-analyses and meta-regressions were performed to explore possible factors of heterogeneity among the studies.Results:A total of 33 studies were included, comprising 7383 ICI- and PPI-treated patients and 8574 ICI-treated and PPI-free patients. The pooled HR was 1.31 (95% CI, 1.19–1.44; p < 0.001) for OS and 1.30 (95% CI, 1.17–1.46; p < 0.001) for PFS, indicating a significant negative association between PPI use and survival in ICI-treated patients. Subgroup meta-analyses by factors including cancer type, ICI type, and time window of PPI use revealed that ICI and PPI use impacted survival in patients with non-small cell lung or urothelial cancer, patients treated with anti-PD-1/PD-L1 antibodies, and patients receiving PPI as baseline treatment or 60 days before ICI treatment initiation.Conclusions:PPI use in patients treated with ICIs was associated with shorter OS and PFS, especially in several specific subgroups of cancer patients. PPIs should be strictly controlled and appear to not impact survival if given temporarily after ICI initiation. These observations could provide the basis for clinical guidelines for concomitant PPI and ICI use.

EFFECTS OF PROTON PUMP INHIBITORS ON THE DEGREE OF DEVELOPMENT OF LIVER ENCEPHALOPATHY IN PATIENTS WITH LIVER CIRROSIS

In this study, we attempted to determine whether proton pump inhibitor (PPI) use in patients with hepatic encephalopathy was predisposed to more severe stages of hepatic encephalopathy according to West Haven criteria. We found that chronic use of PPIs in patients with cirrhosis of the liver and gastroduodenal pathology was associated with significantly higher mean West Haven criteria for hepatic encephalopathy compared with patients who did not use PPIs. Our data also showed that patients with cirrhosis of the liver receiving PPIs have longer hospital stays, with increased morbidity and mortality during their hospital stay.

Вибір оптимального інгібітору протонної помпи для пацієнтів з ішемічною хворобою серця, які потребують проведення подвійної антитромбоцитарної терапії

Висока захворюваність і смертність від серцево-судинних захворювань призвели до необхідності широкого використання антитромбоцитарних засобів у клінічній практиці. Найбільш перспективною вважається комбінована антиагрегантна терапія з використанням препаратів, що мають різні механізми впливу на тромбоцитарну ланку гемостазу, за рахунок чого можна досягти вираженого синергічного ефекту. У нашій країні переважно призначається комбінація ацетилсаліцилової кислоти і клопідогрелю, яку часто називають подвійною антитромбоцитарною терапією (ПАТ). Для зменшення ризиків розвитку шлунково-кишкових ускладнень при використанні ПАТ рекомендований прийом інгібіторів протонної помпи (ІПП), проте в деяких дослідженнях згадується, що одночасне призначення ІПП та клопідогрелю в перспективі підвищує ризик виникнення несприятливих серцево-судинних подій, до яких відносять інфаркт міо-карда, інсульт, нестабільну стенокардію, необхідність повторних коронарних втручань і коронарну смерть. У зв’язку з цим представляється актуальною проблема розробки підходів диференційованого застосування ІПП у пацієнтів, які отримують ПАТ. Надано огляд літератури з означеної вище проблематики, наведено результати досліджень із вивчення впливу різних ІПП на клінічні наслідки у хворих, які приймають клопі-догрель.

Should we routinely prescribe proton pump inhibitors peri-operatively in elderly patients with hip fractures? A review of the literature.

Elderly hip fracture patients are at risk of stress-related gastric mucosal damage, and upper gastrointestinal bleeding is one of the underrecognized but devastating complications.Proton pump inhibitors (PPIs) offer effective prophylaxis against stress-related gastric mucosal damage.Systematic analysis of the literature revealed numerous articles on PPIs and hip fractures, but only three articles dedicated to the analysis of prophylactic use of PPIs in patients with a hip fracture.There is significant reduction in upper gastrointestinal bleeding following PPI prophylaxis and reduced 90-day mortality in elderly hip fracture patients on prophylaxis.PPIs are generally safe, cost-effective and based on available evidence. Their prophylactic use is justifiable in elderly patients with hip fractures.We suggest that PPIs be prescribed routinely peri-operatively in elderly hip fracture patients. Further level-one studies on the subject will allow for firmer recommendations. Cite this article: EFORT Open Rev 2021;6:686-691. DOI: 10.1302/2058-5241.6.200053

Impact of Proton Pump Inhibitor Use on the Effectiveness of Immune Checkpoint Inhibitors in Advanced Cancer Patients.

The gut microbiome plays a critical role in modulating the therapeutic effect of immune checkpoint inhibitors (ICIs). Proton pump inhibitors (PPIs) are commonly used in cancer patients and may affect the gut microbiome by altering gut pH. To evaluate if concurrent use of PPI is associated with overall survival (OS) and progression-free survival (PFS) in patients with stage IV non-small-cell lung cancer (NSCLC), melanoma, renal cell carcinoma, transitional cell carcinoma, or head and neck squamous cell carcinoma. This was a single-center retrospective cohort study of advanced cancer adult patients who received nivolumab or pembrolizumab between September 1, 2014, and August 31, 2019. Concomitant PPI exposure was defined as PPI use 0 to 30 days before or after initiation of ICIs. Treatment outcome was OS and PFS. A total of 233 patients were included in our study. Concomitant PPI use was not significantly associated with OS (hazard ratio [HR] = 1.22; 95% CI = 0.80-1.86) or PFS (HR = 1.05; 95% CI = 0.76-1.45) in patients with ICI use. The effect estimates were robust after adjusting for covariates in multivariate analysis and in patients with NSCLC. Concomitant PPI use was not associated with the effectiveness of nivolumab or pembrolizumab. Certain predictors of survival outcomes related to PPI use in patients receiving immunotherapy, such as the time window and indication of PPI exposure and autoimmune disorders, should be explored in the future to better carve out the impact of PPI on the effectiveness of ICI use.

Evaluation of the Effect of Proton Pump Inhibitors on the Efficacy of Dacomitinib and Gefitinib in Patients with Advanced Non-Small Cell Lung Cancer and EGFR-Activating Mutations.

IntroductionDacomitinib and gefitinib are irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) indicated for the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) and EGFR-activating mutations. Pharmacokinetic (PK) studies in healthy volunteers suggested that acid-reducing drugs such as proton pump inhibitors (PPI) decreased dacomitinib and gefitinib exposure by limiting the pH-dependent absorption. This analysis retrospectively evaluates the effect of concomitant PPI use on dacomitinib exposure and on progression-free survival (PFS) and overall survival (OS) in patients treated with dacomitinib 45 mg QD or gefitinib 250 mg QD in a 1:1 randomized phase 3 study (ARCHER 1050).MethodsThe analysis grouped all patients (n = 452) treated in each arm of the study as non-PPI users, PPI users, or extensive PPI users. PFS and OS data were presented by Kaplan–Meier plots and analyzed using Cox proportional hazards models. Dacomitinib exposure was compared using a linear mixed-effects model.ResultsResults showed that dacomitinib PFS and OS did not differ significantly when comparing PPI users (N = 59) to non-PPI users (N = 152), while extensive PPI users (N = 24) had shorter PFS [hazard ratio (HR): 1.94, p = 0.011] and OS (HR: 1.77, p = 0.027) when compared to non-PPI users. For patients treated with gefitinib, PFS did not differ significantly when comparing PPI users (N = 51) and extensive PPI users (N = 19) to non-PPI users (N = 159); however, both PPI users (HR: 1.65, p = 0.007) and extensive PPI users (HR: 1.70, p = 0.050) had shorter OS when compared to non-PPI users. Further analysis by adjusting potential confounders indicated no statistically significant differences in PFS or OS between any PPI user vs. non-PPI user groups in the dacomitinib and gefitinib arms. PPI use did not appear to affect dacomitinib exposure.ConclusionIn conclusion, PPI use in patients with NSCLC likely has minimal impact on dacomitinib or gefitinib efficacy despite decreased absorption of these drugs observed in PK studies.Trial RegistrationClinicalTrials.gov identifier, NCT01774721

Association of proton pump inhibitors with survival in Veterans with non-small cell lung cancer receiving immunotherapy.

e18729 Background: Proton pump inhibitors (PPI) can disrupt the gut microbiome and thereby modulate response to immunotherapy in cancer patients. In a recently published post-hoc analysis of 757 non-small cell lung cancer (NSCLC) patients receiving atezolizumab pooled from two prospective trials, overall survival (OS) and progression-free survival were significantly lower among the 234 patients receiving PPI. We investigated the impact of PPI in a larger cohort of NSCLC patients treated with ICI within the Veterans Health Administration. Methods: We conducted a nested cohort study of Veterans who were diagnosed with NSCLC between 2010 &amp; 2018 and treated with ICI (immune checkpoint inhibitors). Exposure was defined as receipt of a PPI prescription within 90 days of an ICI infusion. Chi-square tests were used to compare characteristics of exposed versus unexposed Veterans. OS was measured from start of ICI. Cox proportional hazard multivariate (MV) regression was used to calculate hazard ratios (HR) corresponding to variables associated with OS. Results: We identified 3,634 Veterans receiving ICI with non-exclusive exposures to nivolumab (59.3%), pembrolizumab (35.1%), durvalumab (6.9%), and atezolizumab (3.3%). Their median age was 69, and a plurality had male gender (97.0%), white race (73.0%), comorbidity count ≥1 (60.4%), adenocarcinoma (47.8%), and stage IV disease at diagnosis (40.9%). In this nested cohort, 2,159 (59.4%) were exposed to PPI, predominantly omeprazole (1,264 or 85.6% of PPI group). Patients receiving PPI were more likely to be ≤71 years of age, to be white, to reside in rural areas, to have a higher comorbidity burden, to have adenocarcinoma histology, and to receive chemotherapy (all p≤0.04). On MV analysis, PPI use was not significantly associated with detriment in OS (HR 0.96 [0.89-1.04], p= 0.35). In the matched cohort analysis, median survival did not significantly differ between the 1,389 patients taking PPI and the 1,389 without PPI (median 10 versus 10 months, HR 0.98 [0.90-1.06], p= 0.59). Conclusions: In the largest analysis to date of concurrent PPI use in patients with NSCLC receiving ICI, there were no survival differences associated with concomitant PPI use. These results suggest that PPIs do not compromise ICI efficacy.