Risk Of Upper Gastrointestinal Events Research Articles

Risk of gastrointestinal events among patients with sarcoidosis: a population-based study 1976-2013.

Background: An increased risk of gastrointestinal (GI) diseases has been observed in immune-mediated disease but the risk in patients with sarcoidosis is not known. Objectives: This study was undertaken to characterize the risk of GI diseases in patients with sarcoidosis. Methods: A population-based cohort of 345 incident cases of sarcoidosis among Olmsted County, Minnesota residents in 1976-2013 was identified. A cohort of 345 sex and age-matched comparators were also identified from the same underlying population. Medical records of both groups were reviewed for GI diseases. Cox models adjusted for age, sex and calendar year were used to compare the rate of development of GI diseases between the groups. In addition, Cox models were used to evaluate the association between use of immunosuppressive agents and the development of GI diseases among patients with sarcoidosis. Results: GI events occurred in 101 cases and 63 comparators, corresponding to an adjusted hazard ratio (HR) of 1.90 (95% confidence interval [CI] 1.38-2.61). Patients with sarcoidosis had an increased risk for both upper (HR 1.90; 95%CI 1.27-2.83) and lower GI events (HR 1.97; 95%CI 1.27-3.05) relative to comparators. By disease type, patients with sarcoidosis had a significantly elevated risk of upper GI ulcer, upper GI hemorrhage and diverticulitis. Regarding medication use, the only significant association was an increased risk of upper GI events among biologic agent users (HR 11.09; 95%CI 2.16-56.97). Conclusion: Patients with sarcoidosis have a higher risk of both upper and lower GI events compared with subjects without sarcoidosis. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 239-244).

Upper Gastrointestinal Toxicity Associated With Long-Term Aspirin Therapy: Consequences and Prevention

Antiplatelet therapy represents a fundamental part of preventive management for patients who are at risk of a secondary cardiovascular disease (CVD) event. In most cases, the antiplatelet regimen is based on low-dose aspirin, a drug that is highly effective in reducing the incidence of CVD events, but is associated with a substantial risk of gastrointestinal (GI) toxicity. The dyspeptic symptoms, which can result from aspirin administration, and which may occur with or without associated ulceration and bleeding, may lead patients to discontinue therapy, thus increasing their CVD risk. For patients in whom aspirin is indicated and who are deemed to be at increased risk of upper GI events, concomitant therapy with a proton pump inhibitor (PPI) is currently recommended. These agents are highly effective in reducing the upper GI lesions associated with aspirin therapy and have been associated with increased aspirin adherence. However, widespread under-prescribing of PPIs and potential noncompliance with their use means that substantial numbers of patients are at unnecessary risk of upper GI toxicity and—if aspirin therapy is discontinued—CVD events. Provision of aspirin and an immediate-release PPI as a coordinated-delivery combination tablet has been shown to both reduce the risk of gastric ulcer formation and improve patient compliance. This strategy, which may ultimately reduce the incidence of CVD outcomes because of the associated reduction in GI symptoms and the potential for greater patient adherence to aspirin, warrants further investigation under both randomized controlled conditions (explanatory trials), and in real-life settings (pragmatic trials).

Time-trends in the prescribing of gastroprotective agents to primary care patients initiating low-dose aspirin or non-steroidal anti-inflammatory drugs: a population-based cohort study.

Low-dose aspirin (LDA) and non-steroidal-anti-inflammatory drugs (NSAIDs) both increase the risk of upper gastrointestinal events (UGIEs). In the Netherlands, recommendations regarding the prescription of gastroprotective agents (GPAs) in LDA users were first issued in 2009 in the HARM-Wrestling consensus. National guidelines on gastroprotective strategies (GPSs) in NSAID users were issued in the first part of the preceding. The aim of the present study was to examine time-trends in GPSs in patients initiating LDA and those initiating NSAIDs between 2000 and 2012. Within a large electronic primary healthcare database, two cohorts were selected: (i) patients newly prescribed LDA and (ii) patients newly prescribed NSAIDs between 2000 and 2012. Patients who had been prescribed a GPA in the previous six months were excluded. For both cohorts, patients' risk of a UGIE was classified as low, moderate or high, based on the HARM-Wrestling consensus, and the presence of an adequate GPSwas determined. A total of 37 578 patients were included in the LDA cohort and 352 025 patients in the NSAID cohort. In both cohorts, an increase in GPSs was observed over time, but prescription of GPAs was lower in the LDA cohort. By 2012, an adequate GPS was present in 31.8% of high-risk LDA initiators, vs. 48.0% of high-risk NSAID initiators. Despite a comparable risk of UGIEs, GPSs are prescribed less in high-risk LDA initiators than in high-risk NSAID initiators. For both groups of patients, there is still room for improvement in guideline adherence.

Mortality and Readmission Rates After Hospitalization for Upper and Lower Gastrointestinal Events in Quebec, Canada

We determined yearly rates of upper and lower gastrointestinal (GI) hospitalizations in Quebec, Canada and compared the 1-year readmission and mortality risks among those discharged from lower versus upper GI hospitalizations. The burden of serious upper and lower GI events is substantial. Demographic, medical, pharmaceutical, and hospital records were used in a retrospective cohort study to assess risks of mortality and hospital readmission for upper and lower GI events among patients 50 years and older during 1998 to 2006. Among included 39,771 GI hospitalizations, 5238 were from 1998 to 1999, and 5050 from 2005 to 2006. Rates of upper GI hospitalizations decreased in the study period, whereas that of lower GI events did not change. The risk of in-hospital mortality was higher in patients with small bowel versus upper GI events [odds ratio 2.11; 95% confidence interval (CI), 1.81-2.47] and lower in patients with colon/rectal events 0.30 (0.25-0.36). One-year mortality risk after discharge was lower in patients with lower versus upper GI events (small bowel hazard ratio 0.81; 95% CI, 0.70-0.93; and colon/rectal: 0.77; 95% CI, 0.71-0.83). Compared to upper GI events, the risk of hospital readmission was higher in those with small bowel 1.53 (1.19-1.97) and similar in those with colon/rectal events 1.12 (0.96-1.31). The risk of upper GI events may be decreasing, but remains over 3 times as high as that of lower GI events and among those admitted for GI events, about 80% of in-hospital mortality occurred in those with upper GI problems. Although GI events in the small bowel are less frequent than those in upper or lower GI tract, they are the most severe and are associated with higher risks of mortality and hospital readmissions.

Cyclo‐oxygenase‐2 inhibitors or nonselective NSAIDs plus gastroprotective agents: what to prescribe in daily clinical practice?

Two strategies for prevention of upper gastrointestinal (UGI) events for nonselective nonsteroidal anti-inflammatory drug (nsNSAID) users are replacement of the nsNSAID by a cyclo-oxygenase-2-selective inhibitor (coxib) or co-prescription of a gastroprotective agent (GPA). To identify whether and in whom either of these strategies should be preferred in daily practice. A nested case-control study was conducted using three European primary care databases. We selected a cohort including all naive nsNSAID+GPA (≥80% GPA adherence) and coxib users (without GPA use) aged ≥50 years. Cases with an UGI event (i.e. symptomatic UGI ulcer or bleeding) were matched to cohort members without an UGI event on age, sex and number of individual UGI risk factors (i.e. UGI event history, age ≥65 years, concomitant use of anticoagulants, antiplatelets, or glucocorticoids) and calendar time. Conditional logistic regression analysis was used to calculate odds ratios (ORs) with 95% CI, while adjusting for potential confounders. Within the NSAID cohort (n = 617,220), 398 UGI cases were identified. The risk of UGI events was equivalent for coxib and nsNSAID+GPA (≥80% adherence) users (OR: 1.02; 95%CI: 0.77-1.37). In concurrent glucocorticoid users, the risk of UGI events was significantly elevated for nsNSAID+GPA (≥80% adherence) compared with coxib users (OR: 9.01; 95%CI: 1.61-50.50). The risk of UGI events was similar in nsNSAID+GPA (≥80% adherence) and coxibs users. In patients concurrently using glucocorticoids, a significant increase in the risk of UGI events for nsNSAID+GPA users was observed and coxibs should be preferred.

Suboptimal gastroprotective coverage of NSAID use and the risk of upper gastrointestinal bleeding and ulcers: an observational study using three European databases

BackgroundGastro-protective agents (GPA) are co-prescribed with non-steroidal anti-inflammatory drugs (NSAID) to lower the risk of upper gastrointestinal (UGI) events. It is unknown to what extent the protective effect is influenced...

150 Complex Antithrombotic Therapy (CAT) and the Risk of Upper Gastrointestinal Events (UGIE) Among Vulnerable Elders

Background. Cholangiocarcinoma (CCA) is an aggressive epithelial cancer of the biliary tree with survival measured in months. The only potentially curative treatment for CCA is surgical resection. Unfortunately, the vast majority of patients are diagnosed at late stages, when surgery is not an option. MicroRNAs (miRs) are short single stranded RNA sequences, recently shown to have major regulatory functions in cancer. TIMP3 is one of 4 members of the metalloproteinases family and its role was associated with cancer invasion and metastasis. We aimed at elucidating the regulatory mechanisms of TIMP3 in CCA. Methods. Fifteen histologically confirmed CCAs and 9 normal liver specimens were collected at surgery at Johns Hopkins Hospital after informed consent was obtained from all patients. The NLs were obtained at the time of surgery for CCA from normal liver. Quantitative RT-PCR (qRTPCR) for messenger RNA (mRNA) and miRs and quantitative Methylation Specific PCR (qMSP) were performed as previously described. Results. We measured the qRT-PCR level of TIMP3 mRNA and found it to be underexpressed in CCA vs. NL specimens, suggesting a tumor-suppressive role for TIMP3 in the biliary tree. In contrast, our previous work revealed that miR-21 is overexpressed in CCA vs. NL, suggesting a possible negative regulation of TIMP3 by miR-21. In silico searches suggested that TIMP3 is indeed a putative target of miR-21. The CCA cell lines CAK1, TFK1 and HuCCT1 were transfected with a miR-21 inhibitor and TIMP3 protein levels were measured. TIMP3 was significantly elevated in all 3 cell lines transfected with the inhibitor, strongly suggesting that miR-21 downregulates TIMP3 protein levels. Interestingly, miR-21 does not directly bind to TIMP3 mRNA, as evinced by luciferase assays, suggesting the presence of an intermediary molecule or a different mechanism of miR-21 regulation of TIMP3. To investigate a potential co-regulation of TIMP3 in CCA by hypermethylation, we measured the promoter methylation in all 24 specimens. TIMP3 promoter was found to be hypermethylated in only 1/15 CCA (6.6%), 0/3 CCA cell lines and 0/9 NL specimens. Conclusions: TIMP3 mRNA is elevated in NL and decreased in CCA specimens implicating TIMP3 as a tumor suppressor gene in the biliary tree. Our data also suggests that TIMP3 promoter hypermethylation does not appear to play a major role in its downregulation in human CCA specimens. In contrast, miR-21 is a major regulator of TIMP3 in CCA. Furthermore, miR-21 may exert at least part of its oncogenic, pro-invasive effects in CCA by inhibiting TIMP3.

W1926 Serotonin Selective Reuptake Inhibitors (SSRIs) Are Not Associated with An Increased Risk of Upper Gastrointestinal Events in Users of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

W1926 Serotonin Selective Reuptake Inhibitors (SSRIs) Are Not Associated with An Increased Risk of Upper Gastrointestinal Events in Users of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

Effectiveness of National Provider Prescription of PPI Gastroprotection Among Elderly NSAID Users

Our aim was to quantify the effect of provider adherence on the risk of NSAID-related upper gastrointestinal events (UGIE). We identified from national pharmacy records veterans > or = 65 yr prescribed an NSAID, a coxib, or salicylate (>325 mg/day) at any Veterans Affairs (VA) facility (January 1, 2000 to December 31, 2002). Prescription fill data were linked in longitudinal fashion to VA inpatient, outpatient, and death files and merged with demographic, inpatient, outpatient, and provider data from Medicare. Each person-day of follow-up was assessed for exposure to NSAID alone, NSAID+proton pump inhibitor (PPI), coxib, or coxib+PPI. UGIE was defined using our published, validated algorithm. Unadjusted incidence density ratios were calculated for the 365 days following exposure. We assessed risk of UGIE using Cox proportional hazards models, while adjusting for demographics, UGIE risk factors, comorbidity, prescription channeling (i.e., propensity score), geographic location, and multiple time-dependent pharmacological covariates, including aspirin, steroids, anticoagulants, antiplatelets, statins, and selective serotonin reuptake inhibitors. In our cohort of 481,980 (97.8% male, 85.3% white, mean age 73.9, standard deviation 5.6), a safer strategy was prescribed for 19.8%, and 2,753 UGIE occurred in 220,662 person-years of follow-up. When adjusted for prescription channeling, confounders, and effect modification-associated PPI, risk of UGIE was 1.8 (95% confidence interval [CI] 1.6-2.0) on NSAID alone, 1.8 (95% CI 1.5-2.0) on coxib alone, 1.1 (95% CI 0.7-4.6) on NSAID+PPI, and 1.1 (0.6-5.2) on coxib+PPI. When the analysis was adjusted for cumulative percent time spent on a PPI, risk of UGIE decreased from HR 3.0 (95% CI 2.6-3.7) when a PPI was prescribed 0-20% of the time to 1.1 (95% CI 1.0-1.3) when a PPI was prescribed 80-100% of the time. Provider adherence to safer NSAID prescribing strategies is associated with fewer UGIE among the elderly. An adherent strategy lowers, but does not eliminate, risk of an NSAID-related UGIE.

Risk of upper gastrointestinal events with the use of various NSAIDs: A case-control study in a general population

Objective. The gastrointestinal (GI) safety of different non-steroidal anti-inflammatory drugs (NSAIDs) in a real-life setting remains ill defined. The aim of this study was to examine the risk of upper GI events associated with various NSAIDs in a general population. Material and methods. A nationwide, register-based, matched case-control study was carried out in outpatient residents of Finland in 2000–04. Cases with upper GI events (n=9191) were drawn from the Hospital Discharge Register and individually matched to controls (n=41,780) from the Population Register. Results. The semi-selective NSAIDs (nimesulide, nabumetone, meloxicam, etodolac) had the highest odds ratio for upper GI events even after adjusting for various potential confounders (adjusted odds ratio (AOR) 3.63; 95% CI 3.08–4.28), followed by non-selective (2.98; 2.70–3.29) and COX-2 selective NSAIDs (2.53; 2.09–3.07). When the current use of semi-selective NSAIDs was compared with that of non-selective and COX-2 selective NSAIDs, the AORs were 1.54 (1.13–2.09) and 1.67 (1.10–2.53), respectively. The AORs for the use of COX-2 selective NSAIDs did not differ statistically from the non-selective NSAIDs (AOR 0.92; 0.65–1.31). The AORs for individual NSAIDs varied across and within categories. Conclusions. As a group, the GI safety of the COX-2 selective NSAIDs was not demonstrated as definitively superior to non-selective NSAIDs. Semi-selective NSAIDs do not seem to offer any GI advantage over other NSAIDs.

Spironolactone and risk of upper gastrointestinal events: population based case-control study

Spironolactone and risk of upper gastrointestinal events: population based case-control study

Spironolactone and risk of upper gastrointestinal events: population based case-control study

Objective To confirm and quantify any association between spironolactone and upper gastrointestinal bleeding and ulcers.Design Population based case-control study.Setting A primary care information database in the Netherlands.Participants All people on...

Outcomes studies of the gastrointestinal safety of cyclooxygenase-2 inhibitors.

Short-term endoscopic studies of the highly selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) rofecoxib and celecoxib have shown that these agents are well tolerated and have efficacy equivalent to nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) with fewer adverse effects on the upper gastrointestinal (GI) tract. These studies are limited, however, as the detection of endoscopic lesions is not well correlated with symptomatic ulcers and ulcer complications. Outcomes studies of the GI safety are, therefore, essential to understanding how coxibs are likely to perform in a clinical practice setting. Four large outcomes studies (Vioxx Gastrointestinal Outcomes Research, VIGOR; Assessment of Difference Between Vioxx and Naproxen to Ascertain Gastrointestinal Tolerability and Effectiveness trial, ADVANTAGE; Celecoxib Long-term Arthritis Safety Study, CLASS; and the Successive Celecoxib Efficacy and Safety Studies, SUCCESS) examined the GI safety of rofecoxib and celecoxib in over 39,000 patients with osteoarthritis or rheumatoid arthritis. Results of these studies showed that patients taking a supratherapeutic dose of rofecoxib or celecoxib had significantly lower rates of GI-related adverse events than those taking a nonselective NSAID (naproxen, ibuprofen, or diclofenac). Reduced risk of upper GI events was seen in patients with multiple risk factors and in patients using low-dose aspirin and corticosteroids concomitantly with a coxib. Results of large outcomes studies provide support for the COX-2 hypothesis and demonstrate the long-term safety and tolerability of coxibs.

Upper Gastrointestinal Adverse Events and Cyclical Etidronate

PURPOSE: Recently, there have been several published case reports of esophagitis associated with the use of aminobisphosphonates. The objective of this study was to evaluate the upper gastrointestinal (GI) safety of cyclical etidronate, an alkylbisphosphonate, in routine clinical practice.PATIENTS AND METHODS: Information was obtained from 550 general practices in the United Kingdom that provide the medical records to the General Practice Research Database. A group of 7977 cyclical etidronate takers and 2 age-, gender-, and practice-matched control groups (1 with osteoporosis and 1 without) were analyzed.RESULTS: For cyclical etidronate takers, the average age was 71.6 years and total follow-up was 10,328 person-years. The risk of upper GI events (inflammation or ulcer of esophagus, stomach, or duodenum) was comparable between patients taking etidronate and the two control groups. The adjusted relative risk of upper GI events was 0.92 (95% confidence interval [CI] 0.78 to 1.09) for etidronate takers compared with osteoporosis controls and 1.12 (CI 0.91 to 1.37) compared to nonosteoporosis controls. For esophagitis and esophageal ulcers, the relative risks were 0.83 (CI 0.64 to 1.08) and 0.97 (CI 0.71 to 1.31) respectively. The incidence of upper GI events during nonsteroidal anti-inflammatory drug (NSAID), aspirin, or corticosteroid use was similar across the three groups. The upper GI risks of etidronate NSAID users were 0.71 (CI 0.45 to 1.11) and 2.06 (CI 0.98 to 4.35) compared with NSAID users in the two control groups.CONCLUSIONS: These results support the GI tolerability and safety profile of cyclical etidronate in routine clinical practice. Concomitant use of cyclical etidronate with NSAIDs, aspirin, or corticosteroids did not increase the incidence of upper GI events.