Use of proton-pump inhibitors among adults: a Danish nationwide drug utilization study.
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ABSTRACT: Background
The use of proton-pump inhibitors (PPIs) has increased over the last decade. The objective of this study was to provide detailed utilization data on PPI use over time, with special emphasis on duration of PPI use and concomitant use of ulcerogenic drugs.Methods
Using the nationwide Danish Prescription Registry, we identified all Danish adults filling a PPI between 2002 and 2014. Using descriptive statistics, we reported (i) the distribution of use between single PPI entities, (ii) the development in incidence and prevalence of use over time, (iii) measures of duration and intensity of treatment, and (iv) the prevalence of use of ulcerogenic drugs among users of PPIs.Results
We identified 1,617,614 adults using PPIs during the study period. The prevalence of PPI use increased fourfold during the study period to 7.4% of all Danish adults in 2014. PPI use showed strong age dependency, reaching more than 20% among those aged at least 80 years. The proportion of users maintaining treatment over time increased with increasing age, with less than10% of those aged 18-39 years using PPIs 2 years after their first prescription, compared with about 40% among those aged at least 80 years. The overall use of ulcerogenic drugs among PPI users increased moderately, from 35% of users of PPI in 2002 to 45% in 2014.Conclusions
The use of PPIs is extensive and increasing rapidly, especially among the elderly.
SUBMITTER: Pottegard A
PROVIDER: S-EPMC4984329 | biostudies-literature | 2016 Sep
REPOSITORIES: biostudies-literature
Publications
Use of proton-pump inhibitors among adults: a Danish nationwide drug utilization study.
Pottegård Anton A Broe Anne A Hallas Jesper J de Muckadell Ove B Schaffalitzky OB Lassen Annmarie T AT Lødrup Anders B AB
Therapeutic advances in gastroenterology 20160526 5
<h4>Background</h4>The use of proton-pump inhibitors (PPIs) has increased over the last decade. The objective of this study was to provide detailed utilization data on PPI use over time, with special emphasis on duration of PPI use and concomitant use of ulcerogenic drugs.<h4>Methods</h4>Using the nationwide Danish Prescription Registry, we identified all Danish adults filling a PPI between 2002 and 2014. Using descriptive statistics, we reported (i) the distribution of use between single PPI en ...[more]
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Project description:Background:The use of proton-pump inhibitors (PPIs) has grown worldwide, and there are concerns about increased unsubstantiated long-term use. The aim of the study was to describe the real-world use of PPIs over the past decade in an entire national population. Methods:This was a nationwide population-based drug-utilization study. Patterns of outpatient PPI use among adults in Iceland between 2003 and 2015 were investigated, including annual incidence and prevalence, duration of use, and dose of tablet used (lower versus higher), as well as the proportion of PPI use attributable to gastroprotection. Results:We observed 1,372,790 prescription fills over the entire study period, of which 95% were for higher-dose PPIs. Annual incidence remained stable across time (3.3-4.1 per 100 persons per year), while the annual prevalence increased from 8.5 per 100 persons to 15.5 per 100 persons. Prevalence increased with patient age and was higher among women than men. Duration of treatment increased with patients' age (36% of users over 80 years remained on treatment after 1 year compared with 13% of users aged 19-39 years), and was longer among those initiating on a higher dose compared with a lower dose. The proportion of PPI users concurrently using nonsteroidal anti-inflammatory drugs decreased over the study period, while the proportion concurrently using acetylsalicylic acid, oral anticoagulants, or platelet inhibitors increased. Conclusions:In this nationwide study, a considerable increase in overall outpatient use of PPIs over a 13-year period was observed, particularly among older adults. Patients were increasingly treated for longer durations than recommended by clinical guidelines and mainly with higher doses.
| S-EPMC5977421 | biostudies-literature
Project description:Proton pump inhibitors (PPIs) are associated with risk for fracture in osteoporotic adults. In this population-based study, we found a significant association between PPIs and fracture in young adults, with evidence of a dose-response effect. Young adults who use PPIs should be cautioned regarding risk for fracture.Proton pump inhibitors (PPIs) are associated with fracture in adults with osteoporosis. Because PPI therapy may interfere with bone accrual and attainment of peak bone mineral density, we studied the association between use of PPIs and fracture in children and young adults.We conducted a population-based, case-control study nested within records from general medical practices from 1994 to 2013. Participants were 4-29 years old with ? 1 year of follow-up who lacked chronic conditions associated with use of long-term acid suppression. Cases of fracture were defined as the first incident fracture at any site. Using incidence density sampling, cases were matched with up to five controls by age, sex, medical practice, and start of follow-up. PPI exposure was defined as 180 or more cumulative doses of PPIs. Conditional logistic regression was used to estimate the odds ratio and confidence interval for use of PPIs and fracture.We identified 124,799 cases and 605,643 controls. The adjusted odds ratio for the risk of fracture associated with PPI exposure was 1.13 (95% CI 0.92 to 1.39) among children aged < 18 years old and 1.39 (95% CI 1.26 to 1.53) among young adults aged 18-29 years old. In young adults but not children, we observed a dose-response effect with increased total exposure to PPIs (p for trend <0.001).PPI use was associated with fracture in young adults, but overall evidence did not support a PPI-fracture relationship in children. Young adults who use PPIs should be cautioned regarding potentially increased risk for fracture, even if they lack traditional fracture risk factors.
| S-EPMC4575851 | biostudies-literature
Project description:BackgroundPrevious study revealed proton pump inhibitors (PPIs) have an effect on gut microbiota. Alteration of the microbiome causes changes of the host immune system and then induces the development of autoimmune diseases (ADs). This study aimed to explore the possible association between PPIs use and ADs.MethodsThis study was conducted using data from the Taiwan National Health Insurance Research Database in the period between 2002 and 2015. We performed multivariate and stratified analysis through the Kaplan-Meier method and Cox proportional hazard models to estimate the association between proton pump inhibitor use and the risk of autoimmune diseases.ResultsOf the 297,099 patients treated with PPI identified, the overall mean (SD) age was 49.17 (15.63) years and 56.28% of the subjects was male. As compared with the non-PPI group, the adjusted hazard ratio (aHR) were higher for incident organ specific ADs such as Graves disease (aHR=3.28), Hashmoto thyroiditis (aHR=3.61), autoimmune hemolytic anemia (aHR=8.88), immune thrombocytopenic purpura (aHR=5.05) Henoch-Schonlein pupura (aHR=4.83) and Myasthenia gravis (aHR=8.73). Furthermore, the adjusted hazard ratio (aHR) were also higher for incident systemic ADs such as ankylosing spondylitis (aHR=3.67), rheumatoid arthritis (aHR=3.96), primary Sjogren syndrome (aHR=7.81), systemic lupus erythemtoasus (aHR=7.03). systemic vasculitis (aHR=5.10), psoriasis (aHR=2.57), systemic scleroderma (aHR=15.85) and inflammatory myopathy (aHR=37.40). Furthermore, we observed no dose-dependent effect between PPI use and the risk of ADs.ConclusionsOur retrospective population-based cohort study showed that the prescription of proton pump inhibitors is associated with a higher risk of ADs.
| S-EPMC8514990 | biostudies-literature
Project description:To evaluate the characteristics of the prescription of the proton pump inhibitor drugs (PPI) and the adherence to the indications of the guidelines regulating the reimbursement limitations set forth by the Italian Drug Agency.Thirty general practitioners (GP) participated in the study, providing data on more than 40000 patients in total. The population was divided into non occasional users of PPI drugs (PPI users) and non-users (PPI non-users) based on evidence of a prescription of at least 3 packs of PPIs in the last 90 d before analysis. The data provided allowed an assessment of compliance with the requirements of eligibility for PPI reimbursement according to the Italian Drug Agency rules, in order to obtain subpopulations which complied or not with the rules.Six thousand three hundred and twenty-two patients were found to be PPI users, accounting for 14.9% of the patient population. PPI users were more frequently female, older and more frequently diagnosed with gastroesophageal reflux disease, gastric or duodenal ulcers, arthropathy, heart disease and cancer than the rest of the population. PPI users had more frequently received prescriptions for non-steroidal ant-inflammatory drugs (NSAIDS), acetylsalicylic acid (ASA), oral anticoagulant therapy (OAT) and systemic steroids. PPI reimbursement resulted applicable to 69.3% of the PPI users, but a potential for reimbursement of PPI prescriptions was identified in the non PPI users for the treatment of peptic or reflux disease (8.5%) and for the protection of gastric damage caused by NSAIDS (6.1%). Patients who are potentially eligible for reimbursement are older, diagnosed with arthropathy and heart disease more frequently and most commonly receive NSAID and ASA prescriptions compared with PPI users who do not satisfy eligibility requirements. Patients in whom it was not possible to identify conditions related to prescription suitability were more frequently associated with use of OAT.A substantial number of patients who apparently do not meet prescription suitability conditions can be identified, but among non PPI users on the contrary, it is possible to identify an equal number of patients for whom prescription would be suitable. Poor suitability can be identified in the population receiving OAT. Thus, there is scope for decreasing inappropriate use of PPI drugs by adhering to certain criteria and by involving all interested parties.
| S-EPMC5547376 | biostudies-other
Project description:BACKGROUND:Proton-pump inhibitors (PPIs) and clopidogrel are frequently coprescribed, although the benefits and harms of their concurrent use are unclear. OBJECTIVE:To examine the association between concurrent use of PPIs and clopidogrel and the risks for hospitalizations for gastroduodenal bleeding and serious cardiovascular disease. DESIGN:Retrospective cohort study using automated data to identify patients who received clopidogrel between 1999 through 2005 after hospitalization for coronary heart disease. SETTING:Tennessee Medicaid program. PATIENTS:20,596 patients (including 7593 concurrent users of clopidogrel and PPIs) hospitalized for myocardial infarction, coronary artery revascularization, or unstable angina pectoris. MEASUREMENTS:Baseline and follow-up drug use was assessed from automated records of dispensed prescriptions. Primary outcomes were hospitalizations for gastroduodenal bleeding and serious cardiovascular disease (fatal or nonfatal myocardial infarction or sudden cardiac death, stroke, or other cardiovascular death). RESULTS:Pantoprazole and omeprazole accounted for 62% and 9% of concurrent PPI use, respectively. Adjusted incidence of hospitalization for gastroduodenal bleeding in concurrent PPI users was 50% lower than that in nonusers (hazard ratio, 0.50 [95% CI, 0.39 to 0.65]). For patients at highest risk for bleeding, PPI use was associated with an absolute reduction of 28.5 (CI, 11.7 to 36.9) hospitalizations for gastroduodenal bleeding per 1000 person-years. The hazard ratio associated with concurrent PPI use for risk for serious cardiovascular disease was 0.99 (CI, 0.82 to 1.19) for the entire cohort and 1.01 (CI, 0.76 to 1.34) for the subgroup of patients who had percutaneous coronary interventions with stenting during the qualifying hospitalization. LIMITATIONS:Unmeasured confounding and misclassification of exposure (no information on adherence or over-the-counter use of drugs) and end points (not confirmed by medical record review) were possible. Because many patients entered the cohort from hospitals with relatively few cohort members, the analysis relied on the assumption that after adjustment for observed covariates, PPI users from one such hospital could be compared with nonusers from a different hospital. CONCLUSION:In patients with serious coronary heart disease treated with clopidogrel, concurrent PPI use was associated with reduced incidence of hospitalizations for gastroduodenal bleeding. The corresponding point estimate for serious cardiovascular disease was not increased; however, the 95% CI included a clinically important increased risk. PRIMARY FUNDING SOURCE:Agency for Healthcare Research and Quality and National Heart, Lung, and Blood Institute.
| S-EPMC3176584 | biostudies-literature
Project description:Background: The present study aimed to examine the odds of cholangiocarcinoma (CCA) in patients with proton pump inhibitors (PPIs) use. Methods: A nested case-control study design was employed using data obtained from Taiwan's National Health Insurance Research Database. In total, 2,293 patients with confirmed diagnosis of CCA were identified and served as the CCA group. The CCA patients were propensity score-matched with 2,293 subjects without CCA who served as the control group. The cumulative defined daily dose (DDD) of PPIs was calculated based on the total supply in days and quantity of individual PPIs. Univariable and multivariate logistic regression models were used to determine the odds of CCA, and calculated odds ratios (ORs) and 95% confidence intervals (CI) were used to assess PPIs use and odds of CCA. Results: The overall adjusted OR of PPIs use-associated CCA was 2.58 (95% CI 2.27, 2.93). The adjusted OR of CCA by cumulative DDD dose of PPIs and CCA was analyzed and revealed those odds of CCA are associated with all types of PPIs. Conclusions: There were odds of intrahepatic and extrahepatic CCA among PPIs users. All PPIs use was associated with odds of CCA. Analyses of larger numbers of cases are needed to confirm these findings.
| S-EPMC6037835 | biostudies-literature
Project description:BACKGROUND: Most proton pump inhibitors inhibit the bioactivation of clopidogrel to its active metabolite. The clinical significance of this drug interaction is unknown. METHODS: We conducted a population-based nested case-control study among patients aged 66 years or older who commenced clopidogrel between Apr. 1, 2002, and Dec. 31, 2007, following hospital discharge after treatment of acute myocardial infarction. The cases in our study were those readmitted with acute myocardial infarction within 90 days after discharge. We performed a secondary analysis considering events within 1 year. Event-free controls (at a ratio of 3:1) were matched to cases on age, percutaneous coronary intervention and a validated risk score. We categorized exposure to proton pump inhibitors before the index date as current (within 30 days), previous (31-90 days) or remote (91-180 days). RESULTS: Among 13 636 patients prescribed clopidogrel following acute myocardial infarction, we identified 734 cases readmitted with myocardial infarction and 2057 controls. After extensive multivariable adjustment, current use of proton pump inhibitors was associated with an increased risk of reinfarction (adjusted odds ratio [OR] 1.27, 95% confidence interval [CI] 1.03-1.57). We found no association with more distant exposure to proton pump inhibitors or in multiple sensitivity analyses. In a stratified analysis, pantoprazole, which does not inhibit cytochrome P450 2C19, had no association with readmission for myocardial infarction (adjusted OR 1.02, 95% CI 0.70-1.47). INTERPRETATION: Among patients receiving clopidogrel following acute myocardial infarction, concomitant therapy with proton pump inhibitors other than pantoprazole was associated with a loss of the beneficial effects of clopidogrel and an increased risk of reinfarction.
| S-EPMC2659819 | biostudies-other
Project description:Although proton pump inhibitors (PPIs) are widely used, their relative potency and ideal dosing regimens remain unclear. We analyzed data from randomized clinical trials that performed pH testing in patients receiving solid-dose PPI formulations (omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole) for a minimum of 5 days. We used omeprazole equivalency and the surrogate biomarker, percentage time pH > 4 over a 24-hour period (pH4time), to compare PPI effectiveness for different PPIs given once, twice, or 3 times daily. We found that increasing strength of once-daily PPIs (9-64 mg omeprazole equivalents) increased pH4time linearly from approximately 10.0 to 15.6 hours; higher doses produced no further increase in pH4time. Increasing the frequency to twice-daily PPI increased pH4time linearly, from approximately 15.8 to 21.0 hours. Three-times daily PPIs performed similarly to twice-daily PPIs. The costs of PPIs varied greatly, but the cost variation was not directly related to potency. We conclude that PPIs can be used interchangeably based on potency. Using twice-daily PPIs is more effective in increasing efficacy increasing once-daily PPI dosage. Omeprazole and lansoprazole (30 mg) and 20 mg of esomeprazole rabeprazole are functionally equivalent.
| S-EPMC6913203 | biostudies-literature
Project description:BackgroundProton-pump inhibitors (PPIs) are commonly used among medical inpatients, both for prophylaxis against upper gastrointestinal bleeding (UGIB) and continuation of outpatient use. While PPIs reduce the risk of UGIB, they also appear to increase the risk of hospital-acquired pneumonia (HAP) and Clostridium difficile infection (CDI). Depending upon the underlying risks of these conditions and the changes in those risks with PPIs, use of proton-pump inhibitors may lead to a net benefit or net harm among medical inpatients.ObjectiveWe aimed to determine the net impact of PPIs on hospital mortality among medical inpatients.DesignA microsimulation model, using literature-derived estimates of the risks of UGIB, HAP, and CDI among medical inpatients, along with the changes in risk associated with PPI use for each of these outcomes. The primary outcome was change in inpatient mortality.ParticipantsSimulated general medical inpatients outside the intensive care unit (ICU).Main measureChange in overall mortality during hospitalization.Key resultsNew initiation of PPI therapy led to an increase in hospital mortality in about 90% of simulated patients. Continuation of outpatient PPI therapy on admission led to net increase in hospital mortality in 79% of simulated patients. Results were robust to both one-way and multivariate sensitivity analyses, with net harm occurring in at least two-thirds of patients in all scenarios.ConclusionsFor the majority of medical inpatients outside the ICU, use of PPIs likely leads to a net increase in hospital mortality. Even in patients at particularly high risk of UGIB, only those at the very lowest risk of HCAP and CDI should be considered for prophylactic PPI use. Continuation of outpatient PPIs may also increase expected hospital mortality. Apart from patients with active UGIB, use of PPIs in hospitalized patients should be discouraged.
| S-EPMC4803704 | biostudies-literature
Project description:Proton pump inhibitors (PPIs) belong to the most frequently used drugs, also in patients with cirrhosis. PPIs are extensively metabolized by the liver, but practice guidance on prescribing in cirrhosis is lacking. We aim to develop practical guidance on the safe use of PPIs in patients with cirrhosis.A systematic literature search identified studies on the safety (i.e. adverse events) and pharmacokinetics of PPIs in cirrhotic patients. This evidence and data from the product information was reviewed by an expert panel who classified drugs as safe; no additional risks known; additional risks known; unsafe; or unknown. Guidance was aimed at the oral use of PPIs and categorized by the severity of cirrhosis, using the Child-Turcotte-Pugh (CTP) classification.A total of 69 studies were included. Esomeprazole, omeprazole and rabeprazole were classified as having 'no additional risks known'. A reduction in maximum dose of omeprazole and rabeprazole is recommended for CTP A and B patients. For patients with CTP C cirrhosis, the only PPI advised is esomeprazole at a maximum dosage of 20 mg per day. Pantoprazole and lansoprazole were classified as unsafe because of 4- to 8-fold increased exposure. The use of PPIs in cirrhotic patients has been associated with the development of infections and hepatic encephalopathy and should be carefully considered.We suggest using esomeprazole, omeprazole or rabeprazole in patients with CTP A or B cirrhosis and only esomeprazole in patients with CTP C. Pharmacokinetic changes are also important to consider when prescribing PPIs to vulnerable, cirrhotic patients.
| S-EPMC6046475 | biostudies-other