Risk Of Gastrointestinal Events Research Articles

Safety and Efficacy of Istaroxime in Patients With Acute Heart Failure: A Meta-Analysis of Randomized Controlled Trials.

The aim of this study was to assess the efficacy and safety of istaroxime in patients with heart failure.Following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, a search was conducted on the EMBASE and Medline databases to identify articles related to the safety and efficacy of istaroxime in patients with heart failure. The search covered the period from inception to May 31st, 2023, without any restrictions on the year of publication.The search strategy utilized relevant terms such as "istaroxime," "heart failure", "efficacy," and other related terms, along with their corresponding Medical Subject Headings (MeSH) terms.The outcomes assessed in this meta-analysis included the change in left ventricular ejection fraction (LVEF), E to A ratio (a marker of left ventricle function), cardiac index in L/min/m2, systolic blood pressure (SBP) in mmHg, left ventricular end-systolic volume (LVESV) in ml, and left ventricular end-diastolic volume (LVDSV) in ml. For safety analysis, gastrointestinal events and cardiovascular events were assessed. A total of three randomized controlled trials (RCTs) were included in this meta-analysis encompassing 211 patients with heart failure. Pooled analysis showed that istaroxime was effective in increasing LVEF (MD: 1.26, 95% CI: 0.91 to 1.62, p-value: 0.001), reducing E to A ratio(MD: -0.39, 95% CI: -0.60 to -0.19, p-value: 0.001), increasing cardiac index(MD: 0.22, 95% CI: 0.18 to 0.25, p-value: 0.001), reducing LVESV (MD: -11.84, 95% CI: -13.91 to -9.78, p-value: 0.001), reducing LVEDV (MD: -12.25, 95% CI: -14.63 to -9.87, p-value: 0.001) and increasing SBP (MD: 8.41, 95% CI: 5.23 to 11.60, p-value: 0.001) compared to the placebo group. However,risk of gastrointestinal events was significantly higher in patients receiving istaroxime compared to the placebo group (RR: 2.64, 95% CI: 1.53 to 4.57, p-value: 0.0005). These findings support the enhancement of heart function with istaroxime administration, aligning with previous clinical and experimental evidence.

Is colchicine safe for cardiovascular indications?

Abstract Background Colchicine has an emerging role in the cardiovascular field (e.g. acute and chronic coronary syndromes, pericarditis, atrial fibrillation), although, concerns for side effects, especially gastrointestinal, may limit its prescription. Aims We aimed at evaluating reported side effects of colchicine for cardiovascular indications. Methods We performed a meta-analysis of published randomized controlled trials on colchicine for the treatment of cardiovascular diseases. Random-effects meta-analysis was used to assess the risk of adverse events and drug withdrawal. Publication bias was assessed using the Egger test, and meta-regression was performed to assess sources of heterogeneity. Results Among 14 188 patients, 7136 patients received colchicine while the other 7052 received placebo. The occurrence of any adverse event with colchicine was reported in 15.3 vs. 13.9% patients [relative risk (RR) 1.26, 95% confidence interval (CI) 0.96–1.64, P=0.09, see figure]. Gastrointestinal events were reported in 16.1 vs. 12.2% (RR 2.16, 95% CI 1.50–3.12, P<0.001), while diarrhoea was reported in 12.5 vs. 8.1% (RR 2.77, 95% CI 1.55–4.94, P<0.001). The risk of gastrointestinal events increased with daily dose and shorter treatment duration. Myalgias were observed in 21 vs. 18% patients (RR 1.16, 95% CI 1.02–1.32, P=0.03). Other adverse events such as myotoxicity, hepatic adverse events, hematologic adverse events, cutaneous adverse events, infection or death were not increased by colchicine treatment. Colchicine discontinuation was reported in 4.8 vs. 3.4% patients (RR 1.54, 95% CI 1.20–1.99, P<0.001). Conclusions Colchicine is associated with increased risk of gastrointestinal events and myalgias, but not of other adverse events. The risk of gastrointestinal events may be avoided with lower dose (0.5 mg/daily) and is inversely related to treatment duration, possibly due to early drug discontinuation or drug tolerance. Funding Acknowledgement Type of funding sources: None.

Adverse events of colchicine for cardiovascular diseases: a comprehensive meta-analysis of 14 188 patients from 21 randomized controlled trials.

Colchicine has an emerging role in the cardiovascular field, although, concerns for side effects, especially gastrointestinal, limit its prescription. We aimed at evaluating reported side effects of colchicine for cardiovascular indications. We performed a meta-analysis of published randomized controlled trials on colchicine for the treatment of cardiovascular diseases. Random-effects meta-analysis was used to assess the risk of adverse events and drug withdrawal. Publication bias was assessed using the Egger test, and meta-regression was performed to assess sources of heterogeneity. Among 14 188 patients, 7136 patients received colchicine while the other 7052 received placebo. The occurrence of any adverse event with colchicine was reported in 15.3 vs. 13.9% patients [relative risk (RR) 1.26, 95% confidence interval (CI) 0.96-1.64, P = 0.09]. Gastrointestinal events were reported in 16.1 vs. 12.2% (RR 2.16, 95% CI 1.50-3.12, P < 0.001), while diarrhea was reported in 12.5 vs. 8.1% (RR 2.77, 95% CI 1.55-4.94, P < 0.001). The risk of gastrointestinal events increased with daily dose and shorter treatment duration. Myalgias were observed in 21 vs. 18% patients (RR 1.16, 95% CI 1.02-1.32, P = 0.03). Other adverse events such as myotoxicity, hepatic adverse events, hematologic adverse events, cutaneous adverse events, infection or death were not increased by colchicine treatment. Colchicine discontinuation was reported in 4.8 vs. 3.4% patients (RR 1.54, 95% CI 1.20-1.99, P < 0.001). Colchicine is associated with increased risk of gastrointestinal events and myalgias, but not of other adverse events. The risk of gastrointestinal events may be avoided with lower dose (0.5 mg/daily) and is inversely related to treatment duration, possibly due to early drug discontinuation or drug tolerance.

P0865A QUALITATIVE STUDY OF PATIENTS' PREFERENCE FOR THE TREATMENT OF ANAEMIA ASSOCIATED WITH CHRONIC KIDNEY DISEASE

Abstract Background and Aims Anaemia is a common complication of chronic kidney disease (CKD) that is associated with fatigue, shortness of breath, and lethargy. CKD anaemia is commonly treated with oral or intravenous (IV) iron and IV or subcutaneous (SC) erythropoiesis-stimulating agents (ESAs). The objectives of this study were to understand patients’ experiences with CKD anaemia and their preferences related to treatment. Method Qualitative 60-minute semi-structured interviews were conducted with ESA-treated adult CKD patients with anaemia, either non–dialysis-dependent (ND) or dialysis-dependent (DD), and with practicing nephrologists in France, Germany, Spain, the UK, and Japan. The patients’ interviews, appropriately tailored for ND and DD patients, comprised three sections: 1) patients’ views on the burden of the disease and its treatment; 2) discussion of vignettes describing different treatment options; and 3) non-experimental choice questions between two hypothetical treatments including mode of administration, need for iron supplement, and risk of adverse events (AEs). Results A total of 51 patients were enrolled (ND, n=6 per country except for France [n=7]; DD [haemodialysis or peritoneal dialysis], n=4 per country). Two nephrologists per country were interviewed. The most commonly reported symptoms associated with anaemia were tiredness (ND, 77%; DD, 85%) and shortness of breath (ND, 42%; DD, 30%); these two symptoms were also reported by nephrologists, who considered clinical efficacy the most important aspect of treatment. In Japan, dizziness was the most common (n=5/6, 83%) symptom among ND patients. Anaemia symptoms were reported to negatively affect different aspects of patients’ lives, including the ability to carry out daily activities (ND, 61%; DD, 65%), work (ND, 42%; DD, 50%), and exercise (ND, 26%; DD, 30%). ESA treatments were perceived to be effective in improving patients’ symptoms and quality of life. Many patients had not experienced AEs associated with treatment and were not concerned about them, however patients who had experienced gastrointestinal (GI) AEs due to oral iron were sensitive to the risk of GI effects. Out of 23 ND patients who were asked, 19 (83%) preferred an oral treatment due to the convenience of administration, and to avoid injection pain and drug storage requirements associated with SC administration. Self-administering SC ESAs was a concern among Japanese ND patients, who often had a healthcare professional administer the medication. Haemodialysis patients (n=12), who often receive IV ESAs during their dialysis sessions, were less likely to prefer oral treatments due to lack of perceived convenience. Peritoneal dialysis patients (n=8), who often receive home dialysis and SC ESAs, preferred oral treatment to avoid self-administration and storage requirements, and to make travel easier. Limitations of the study included the small number of participants and amendments to the eligibility criteria implemented during data collection, including more relaxed requirements for blood pressure, blood transfusion, and insulin use. Conclusion Patients considered the available treatment options to effectively treat CKD anaemia. Besides efficacy, patients’ primary concern was the mode of administration of their medication, rather than safety considerations.

Risk of Gastrointestinal Events During Lapatinib Therapy: A Meta-Analysis From 12,402 Patients With Cancer.

Lapatinib, a tyrosine kinase inhibitor used as an anticancer therapeutic agent, has adverse events associated with treatment resulting in noncompliance and withdrawal from the therapy. Here, we performed meta-analysis of published clinical trials to determine relative risk (RR) and incidence of gastrointestinal events during lapatinib therapy in patients with cancer. A comprehensive literature search was performed and summary incidence, RR, and 95% confidence intervals (CI) were calculated using fixed-effects or random-effects models, depending on the heterogeneity of trials. Thirty-six trials with 12,402 patients were included; summary incidences of all-grade gastrointestinal events in patients with cancer were diarrhea 57.8%, nausea 30.8%, and vomiting 19.6%. Lapatinib combination with chemotherapy or any anti-HER2 mAbs were associated with significant risk of all-grade diarrhea [(RR 3.64, 95% CI, 2.96-4.49), (RR 2.89, 95% CI, 2.21-3.79), respectively] and high-grade diarrhea [(RR 11.25, 95% CI, 7.31-17.33), (RR 9.96, 95% CI, 7.23-13.72), respectively], and lapatinib combination with chemotherapy group showed a significantly increased risk of all-grade nausea (RR 1.54, 95% CI, 1.25-1.89). Lapatinib combination with chemotherapy or any anti-HER2 mAbs were associated with significant risk of all-grade vomiting [(RR 1.47, 95% CI, 1.12-1.93), (RR 1.30, 95% CI, 1.11-1.52), respectively]. Lapatinib combination with any anti-HER2 mAbs was associated with a significant risk of high-grade vomiting (RR 2.25, 95% CI, 1.41-3.61). This study revealed a significantly increased risk of diarrhea, nausea, and vomiting in patients with cancer receiving lapatinib, suggesting that appropriate clinical intervention and gastrointestianal protective agents should be emphasized.

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).

Risk of gastrointestinal events with newly approved (after 2011) vascular endothelial growth factor receptor tyrosine kinase inhibitors in cancer patients: a meta-analysis of randomized controlled trials.

We performed a meta-analysis to systematically review the gastrointestinal (GI) events (diarrhea, nausea, vomiting, anorexia) of five newly approved (after 2011) VEGFR-TKIs in cancer patients. The relevant studies of the randomized controlled trials (RCTs) in cancer patients treated with cabozantinib, vandetanib, lenvatinib, regorafenib, and axitinib were retrieved and the systematic evaluation was conducted. Forty-one randomized controlled trials and 10,860 patients were included. Current analysis suggested that the use of these agents increased the risk of all-grade and high-grade GI events, and the diarrhea was the most common GI events. The risk of all-grade and high-grade GI events varies significantly within drug types, tumor types, and VEGFR-TKIs-based regimens. The available data suggested that the use of the five newly approved VEGFR-TKIs may increase risk of GI events in cancer patients. Physicians and patients should be aware of these risks and frequent monitoring and careful management should be emphasized when managing these VEGFR-TKIs.

Risk of Gastrointestinal Events During Vandetanib Therapy in Patients With Cancer: A Systematic Review and Meta-analysis of Clinical Trials.

Vandetanib, a tyrosine kinase inhibitor used as an anticancer therapeutic agent, has adverse events associated with treatment resulting in noncompliance and withdrawal from the therapy. Here, we performed meta-analysis of published clinical trials to determine relative risk (RR) and incidence of gastrointestinal events during vandetanib therapy in patients with cancer. A comprehensive literature search was performed and summary incidence, RR, and 95% confidence intervals (CIs) were calculated employing fixed- or random-effects models, depending on the heterogeneity of trials. Twenty-two trials with 6382 patients were included summary incidences of all-grade gastrointestinal events in patients with cancer were anorexia 24% (95% CI, 20%-28%), constipation 17% (95% CI, 13%-20%), diarrhea 46% (95% CI, 40%-53%), nausea 29% (95% CI, 25%-33%), and vomiting 17% (95% CI, 14%-21%). Incidences of vandetanib-associated gastrointestinal events stratified by tumor histology were statistically insignificant. Vandetanib was associated with a significant risk of all-grade diarrhea (RR 1.75, 95% CI, 1.42-2.16) and high-grade diarrhea (RR 1.94, 95% CI, 1.43-2.64) and significantly decreased risk of all-grade constipation (RR 0.80, 95% CI, 0.71-0.91). Summary RR showed a significant risk of vandetanib-associated constipation (RR 0.82, 95% CI, 0.72-0.93) and diarrhea (all-grade: RR 1.68, 95% CI, 1.31-2.14 and high-grade: RR 1.57, 95% CI, 1.14-2.17) in patients with non-small-cell lung cancer. This study revealed a significantly increased risk of diarrhea and a reduced risk of constipation in patients with cancer receiving vandetanib, suggesting that appropriate and frequent clinical monitoring should be emphasized.

Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis

BackgroundThe cardiovascular safety of celecoxib, as compared with nonselective nonsteroidal antiinflammatory drugs (NSAIDs), remains uncertain.MethodsPatients who required NSAIDs for osteoarthritis or rheumatoid arthritis and were at increased cardiovascular risk were randomly assigned to receive celecoxib, ibuprofen, or naproxen. The goal of the trial was to assess the noninferiority of celecoxib with regard to the primary composite outcome of cardiovascular death (including hemorrhagic death), nonfatal myocardial infarction, or nonfatal stroke. Noninferiority required a hazard ratio of 1.12 or lower, as well as an upper 97.5% confidence limit of 1.33 or lower in the intention-to-treat population and of 1.40 or lower in the on-treatment population. Gastrointestinal and renal outcomes were also adjudicated.ResultsA total of 24,081 patients were randomly assigned to the celecoxib group (mean [±SD] daily dose, 209±37 mg), the naproxen group (852±103 mg), or the ibuprofen group (2045±246 mg) for a mean treatment duration of 20.3±16.0 months and a mean follow-up period of 34.1±13.4 months. During the trial, 68.8% of the patients stopped taking the study drug, and 27.4% of the patients discontinued follow-up. In the intention-to-treat analyses, a primary outcome event occurred in 188 patients in the celecoxib group (2.3%), 201 patients in the naproxen group (2.5%), and 218 patients in the ibuprofen group (2.7%) (hazard ratio for celecoxib vs. naproxen, 0.93; 95% confidence interval [CI], 0.76 to 1.13; hazard ratio for celecoxib vs. ibuprofen, 0.85; 95% CI, 0.70 to 1.04; P<0.001 for noninferiority in both comparisons). In the on-treatment analysis, a primary outcome event occurred in 134 patients in the celecoxib group (1.7%), 144 patients in the naproxen group (1.8%), and 155 patients in the ibuprofen group (1.9%) (hazard ratio for celecoxib vs. naproxen, 0.90; 95% CI, 0.71 to 1.15; hazard ratio for celecoxib vs. ibuprofen, 0.81; 95% CI, 0.65 to 1.02; P<0.001 for noninferiority in both comparisons). The risk of gastrointestinal events was significantly lower with celecoxib than with naproxen (P=0.01) or ibuprofen (P=0.002); the risk of renal events was significantly lower with celecoxib than with ibuprofen (P=0.004) but was not significantly lower with celecoxib than with naproxen (P=0.19).ConclusionsAt moderate doses, celecoxib was found to be noninferior to ibuprofen or naproxen with regard to cardiovascular safety. (Funded by Pfizer; ClinicalTrials.gov number, NCT00346216.)

Prescription behavior for gastroprotective drugs in new users as a result of communications regarding clopidogrel - proton pump inhibitor interaction.

Safety concerns of the concomitant use of clopidogrel and proton pump inhibitors (PPIs) were published in 2009 and 2010 by the medicines regulatory agencies, including a direct healthcare professional communication. We examined the association between various safety statements and prescription behavior for gastroprotective drugs in naïve patients in the Netherlands during the years 2008–2011. Data from the PHARMO Database Network were analyzed with interrupted time series analyses to estimate the impact of each communication on drug prescriptions. Dispensings were used as a proxy variable for prescription behavior. After the early communication in January 2009, 15.5% (95% CI 7.8, 23.4) more patients started concomitantly with (es)omeprazole and 13.8% (95% CI 6.5, 21.2) less with other PPIs. Directly after the first statement in June 2009, we found a steep increase in histamine 2‐receptor antagonists (H2RA) peaking at 25%, placing those patients at risk for gastrointestinal events. This effect for H2RA faded away after a few months. In February 2010, when the official advice via an adjusted statement was to avoid (es)omeprazole, we found a decrease of 11.9% (95% CI 5.7, 18.2) for (es)omeprazole and an increase of +16.0% (95% CI 10.3, 21.7) for other PPIs. Still 22.6% (95% CI 19.5, 25.7) of patients started on (es)omeprazole in February 2010, placing them at risk for cardiovascular events. Advices of regulatory authorities were followed, however, reluctantly and not fully, probably partly because of the existing scientific doubt about the interaction.

Abstract 124: Bridging Clinical Trial and Community-Based Cardiovascular Outcomes With Antiplatelet Therapy: An Analysis of Cardiovascular Outcomes in a Phase 3 Long-Term Safety Study of PA32540 Compared to a Matched Community-Based Sample

Background: Improvements in antiplatelet strategies could have a significant impact on cardiovascular (CV) events. PA32540 is a novel single-dose tablet of 325 mg enteric-coated aspirin and 40 mg immediate-release omeprazole developed to significantly reduce upper gastrointestinal (UGI) toxicity and discontinuation due to aspirin-associated UGI symptoms. In order to bridge the potential clinical benefits of PA32540 to a broader community setting, we compared CV and gastrointestinal (GI) outcomes from a long-term, open-label PA32540 Phase 3 clinical trial to CV and GI outcomes in a community setting (CS). Objective: To assess 2 clinically and demographically matched patient populations receiving treatment for secondary CV prevention: one group treated with PA32540, and the other group treated with standard antiplatelet therapy. Methods: All patients were receiving secondary CV preventive therapy and were at risk for GI events. Patients (n=379) from a 12-month Phase 3 open-label clinical trial of PA32540 were matched to CS patients (n=379) prescribed antiplatelet therapy following an index CV event from a retrospective (2001-2010) claims analysis database. Patients were matched on clinical and demographic variables that included gender, age (±2 years), history of proton pump inhibitor use, and nonsteroidal anti-inflammatory drug use. The relationship between CV outcomes and multiple demographic variables (eg, age, race, comorbidities) were examined. Results: Within 12 months of initiating preventive secondary CV therapy, 18% (68/379) of CS patients and 13% (49/379) of PA32540 patients experienced a secondary CV event. This corresponds to a 28% reduction of reported CV events compared with similar CS patients (Figure). Similarly, the proportion of patients experiencing a serious GI event was 3.7% (14/379) in the CS group and 0.8% (3/379) in the PA32540 group; a 78.6% reduction. Conclusions: Fewer CV and GI events occurred among the open-label Phase 3 clinical trial patients treated with PA32540 than among the matched population of CS patients receiving antiplatelet therapy. These data suggest that a further reduction in secondary CV outcomes may be achieved by reducing aspirin-associated UGI symptoms that may lead to discontinuation of antiplatelet therapy.

ASSESSMENT OF RISK FOR GASTROINTESTINAL AND CARDIOVASCULAR COMPLICATIONS ASSOCIATED WITH THE USE OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS IN THE CIS POPULATION: PRELIMINARY DATA OF THE CORONA-2 EPIDEMIOLOGICAL SURVEY

Nonsteroidal anti-inflammatory drugs (NSAIDs) are able to effectively control the major symptoms of rheumatic diseases and widely used in real clinical practice. However, they may cause serious gastrointestinal (GI) and cardiovascular (CV) events. The prevention of these events is based on the estimation of whether risk factors (RFs) are present. Objective: to estimate the presence of RFs in patients needing NSAIDs. Subjects and methods . A cross-sectional epidemiological survey was performed, during which 2021 physicians from 9 CIS countries questioned for 2 weeks at least 10 patients needing NSAIDs. The inclusion criterion was severe musculoskeletal pain (>40 mm on a 100-mm visual analogue scale (VAS)) or use of NSAIDs at the examination. Data were obtained on 21,185 patients (57.5% women and 42.5% men) (mean age 50.5±14.1 years) who had predominantly dorsalgia (56.6%) and osteoarthritis (23.5%). The mean pain value was 62.2±25.2 mm. Results. 1.7, 11.3, and 25.3% of patients had history of gastrointestinal bleeding, ulcer, or dyspepsia, respectively; people over 65 years of age constituted 16.8%; those who took low-dose aspirin (LDA) – 20.0%. The total number of patients at high risk for GI events was 29.0%. There were also common CV RFs: myocardial infarction or stroke (7.8%), coronary heart disease (17.8%), hypertension (37.7%), and diabetes mellitus (8.1%). The total number of patients at high risk for CV events (without SCOR assessment) was 23.0%. Many high-risk patients who has already used NSAIDs received no effective prevention. Thus, 62.2% of the patients at high GI risk took gastroprotective drugs; 53.2% of those at high CV risk used LDA. Conclusion. A large number of patients needing active analgesic therapy have a serious risk for drug-induced complications. This limits the possibility of using NSAIDs and determines the need for effective prevention or use of alternative methods for analgesia.

Gastrointestinal comorbidities associated with atrial fibrillation.

This observational study was conducted to describe the risk of gastrointestinal (GI) events among patients with atrial fibrillation (AF). We analyzed Thomson Reuters MarketScan® data from 2005 to 2009. Subjects aged ≥18 years with ≥ 1 AF diagnosis were selected. GI events were identified from claims with a primary or secondary diagnosis code for any GI condition. The risk of GI events was assessed using cumulative incidence (new GI events/patients with AF without GI condition at baseline) and incidence rates (IRs), calculated as the number of patients with new GI events divided by patient-years of observation. In addition, the CHADS2 score was evaluated at baseline to determine the patient’s risk of stroke. A total of 557,123 AF patients were identified. The mean (median) AF patient age was 68.2 years (70); 45% were female. The cumulative incidences of any GI event and dyspepsia were 40% and 19%, respectively. The corresponding IRs were 38.8 and 14.7 events per 100 patient–years. IRs of any GI events for female and male patients were 43.6 and 35.5; for patients in the age groups <65, 65–74, 75–84, and ≥85 years, IRs were 32.3, 38.9, 44.6, and 52.7; for patients with a CHADS2 score of 0, 1–2, 3–4, and 5–6, IRs were 30.3, 41.6, 56.9, and 74.5, respectively. In this large claims database, 40% of AF patients experienced a GI event, predominantly dyspepsia. Physicians should take age and comorbidities into consideration when managing AF patients.Electronic supplementary materialThe online version of this article (doi:10.1186/2193-1801-3-603) contains supplementary material, which is available to authorized users.

Risk of gastrointestinal events with sorafenib, sunitinib and pazopanib in patients with solid tumors: A systematic review and meta‐analysis of clinical trials

Gastrointestinal (GI) events have been described with sorafenib, sunitinib and pazopanib in cancer patients. We performed an up-to-date meta-analysis to determine the incidence and relative risk (RR) in patients with cancer treated with these agents. PubMed databases were searched for articles published till May 2013. Eligible studies were selected according to PRISMA statement. Summary incidence, RR, and 95% CIs were calculated using random-effects or fixed-effects models based on the heterogeneity of selected studies. A total of 6,447 patients were available for the meta-analysis; 2,260 had renal cell carcinoma (RCC) and 4,187, 1,691 non-small cell lung cancers, 599 hepatocellular cancers, 1,066 breast cancers, 165 neuroendocrine tumors, 304 gastrointestinal stromal tumors and 362 soft tissue sarcomas. Diarrhea was the most common GI event. When stratified by tumor type (RCC vs. non-RCC), the difference among the incidences of GI events was significant for diarrhea (p < 0.001) and vomiting (p = 0.006), that resulted higher in RCC patients. In RCC patients, sorafenib registered the lower incidence and RR of all grades GI events. The difference was statistically significant for sorafenib versus sunitinib-related all and high-grade events (p < 0.001) and for sorafenib versus pazopanib all grades GI events (p < 0.001) and high-grade anorexia (p < 0.001). Treatment with VEGFR TKIs sorafenib, sunitinib and pazopanib is associated with a significant increase in the risk of GI events in patients with cancer, and frequent clinical monitoring should be emphasized when managing these three and newer VEGFR TKIs.

Long-Term Safety of PA32540, a Coordinated Delivery Tablet of 325 mg of Enteric-Coated Aspirin and 40 mg of Immediate-Release Omeprazole in Secondary Cardiovascular Patients at Risk for Gastrointestinal Events

Long-Term Safety of PA32540, a Coordinated Delivery Tablet of 325 mg of Enteric-Coated Aspirin and 40 mg of Immediate-Release Omeprazole in Secondary Cardiovascular Patients at Risk for Gastrointestinal Events

Failure to Renew Prescriptions for Gastroprotective Agents to Patients on Continuous Nonsteroidal Anti-inflammatory Drugs Increases Rate of Upper Gastrointestinal Injury

Patients with risk factors for gastrointestinal (GI) disorders who continuously use nonsteroidal anti-inflammatory drugs (NSAIDs) also should take gastroprotective agents (GPAs), such as proton pump inhibitors (PPIs). However, it is not clear how many physicians continue to prescribe GPAs to these patients, and whether stopping the GPA prescription increases GI complications. We performed a retrospective, observational, longitudinal study using a validated electronic database of representative general practitioners in France. We analyzed data for 1856 patients at risk for GI events (>65 y, past history of GI ulcer, or receiving antiplatelet agents) who received prescriptions for an NSAID and PPI from 2007 to 2009. Kaplan-Meier curves were used to determine the probability of still being prescribed a GPA at 12 and 24 months after the first prescription. Multivariate logistic regression analysis was used to identify factors associated with nonpersistence. GI complication rates were compared using the Student t test. The probability of still being prescribed a PPI along with an NSAID 1 year after the study began was 77.5% (95% confidence interval [CI], 75.6%-79.4%) and 68.3% after 2 years (95% CI, 66.1%-70.4%). Risk factors for no longer receiving a prescription for a PPI included switching to a cyclooxygenase-2-selective inhibitor (hazard ratio [HR], 2.50; 95% CI, 1.91-3.28; P < .001) or to a nonselective NSAID (HR, 1.63; 95% CI, 1.33-1.99; P < .001), and female sex (HR, 1.25; 95% CI, 1.05-1.45; P < .05). In 50% of these cases, the PPI was reintroduced within 6 months, without a specific reason in 70% of the cases. The risk for upper GI injury was higher among patients with discontinued prescriptions for PPIs (odds ratio, 1.45; 95% CI, 1.06-2.09; P = .02). Within 2 years after prescribing a PPI, physicians do not renew this prescription for approximately 33% of patients receiving continuous NSAIDs. This increases the risk for GI adverse events among these patients.

Risk of Gastrointestinal Events in Patients with Rheumatoid Arthritis After Withdrawal of Rofecoxib

To examine the incidence of gastrointestinal (GI) events in patients with rheumatoid arthritis (RA) after the removal of rofecoxib from the market. Residents of British Columbia with a diagnosis of RA who were chronic users of cyclooxygenase 2 (COX-2) inhibitors or nonselective nonsteroidal antiinflammatory drugs (nsNSAID) as of September 30, 2004, were included. We studied the risk of GI events using incidence rates and adjusted HR from Cox proportional hazards regression using time-dependent covariates. The cohort comprised 4266 patients with a mean age of 60 years and over 72% women, of which 2034 (48%) were classified as COX-2 inhibitor users and 2232 (52%) as chronic nsNSAID users as of September 30, 2004. The 2 groups were well balanced on baseline covariates except for comorbid conditions. In the year following rofecoxib withdrawal, 174 patients (5.5%) experienced 1 or more GI events, defined as a GI-related physician visit or hospitalization. There was no statistically significant increase in the risk of a GI event between those classified as a COX-2 inhibitor or nsNSAID user at the time of withdrawal (HR 1.03, 95% CI 0.69-1.54). Considering the drug exposure at the time of the event, there was no increased risk of GI events associated with the use of either COX-2 inhibitors or nsNSAID, or with the use of oral corticosteroids, low-dose aspirin, or clopidogrel, after adjustment for potential confounders. In this cohort, withdrawal of rofecoxib did not result in a significant increase in GI events among patients with RA.

HZT-501 (DUEXIS®; ibuprofen 800 mg/famotidine 26.6 mg) gastrointestinal protection in the treatment of the signs and symptoms of rheumatoid arthritis and osteoarthritis

Arthritis affects nearly 50 million people in the USA and, with the aging of the population, the prevalence is expected to rise. While NSAIDs are very effective in relieving pain associated with osteoarthritis (OA) and rheumatoid arthritis (RA), they are associated with side effects, including gastrointestinal (GI) toxicity, which may manifest as dyspepsia, ulcers and/or bleeding. A number of approaches have been employed in an effort to either completely avoid or reduce the risk of GI toxicities associated with NSAID use. Two new products combining an NSAID with a gastroprotective agent have recently been approved and other agents are in the pipeline. Patient adherence to prescribed gastroprotective therapy is known to be poor, often resulting in an increased risk of GI events in patients taking NSAIDs. These newer combination products may fulfill an important need for many patients who need to receive NSAIDs for the pain of OA and RA, but who are also at risk of upper GI events. This article reviews preclinical and clinical results for a new fixed-dose combination of ibuprofen and famotidine, DUEXIS® (HZT-501), which has recently been approved in the USA for the relief of signs and symptoms of RA and OA and to decrease the risk of developing upper GI ulcers.

IMPACT OF CO-MORBID CONDITIONS ON CARDIAC STRUCTURE AND FUNCTION IN HYPERTENSIVE PATIENTS

Background: The patient with cardiovascular disease and antiplatelet therapy who develops a peptic ulcer bleeding requires a complex approach. We aimed to show the therapeutic strategy for these patients adopted in “Floreasca” Emergency Hospital in accordance with current data in the literature. Methods: We analyzed medical data recorded between January 1 and December 31, 2010 in “Floreasca” Emergency Hospital for patients with peptic ulcer bleeding and antiplatelet therapy. We also assessed the results of recent clinical trials and the current guidelines for the treatment of these patients. Results: Patients with peptic ulcer bleeding and antiplatelet therapy have an increased risk of major adverse cardiac events and a significant increase in risk of 30-day all-cause mortality associated with the withdrawal of antiplatelet agents. Conclusion: Individual assessment of cardiovascular and gastrointestinal risks is indicated for each patient. Early reintroduction of antiplatelet therapy should be considered when vascular risk appears to outweigh the risk of gastrointestinal events (usually within 7 days). In these cases, antiplatelet agents resumption should be associated with effective endoscopic hemostasis, proton pomp inhibitors and eradication of Helicobacter pylori, if that infection is demonstrated.

108 Risk Factors for Acute GI Bleeding Following Myocardial Infarction in Patients Who are Prescribed Clopidogrel

G A A b st ra ct s was defined as the composite of myocardial infarction, unstable angina pectoris, stroke and/ or all-cause mortality. Peptic ulcer disease was also used as primary gastrointestinal outcome. The presence of risk factors for cardiovascular and gastrointestinal complications was identified for each subject during a 1-year history period prior to index date. These included all diagnoses, procedures and treatments reimbursed by the health insurance. Cox proportional hazard regression analysis was used to calculate the risk of cardiovascular and gastrointestinal outcomes in clopidogrel patients with or without PPI use. Results: A total of 18,139 new clopidogrel users were identified, of whom 5,734 (32%) used PPIs concurrently. Patients on PPIs were significantly older, used more co-medications and suffered from more comorbidities. Use of clopidogrel and PPIs was associated with an increased risk of myocardial infarction (HR 1.93, 95% CI 1.40-2.65), unstable angina pectoris (HR 1.79, 95% CI 1.602.03) and the composite cardiovascular endpoint (HR 1.75, 95% CI 1.58-1.94) compared to clopidogrel users without PPIs. PPI users also had an increased risk of gastrointestinal events compared those not using PPIs (HR 4.76, 95%CI 1.18-19.17). No significant differences were found between different types of PPIs and associated risks of adverse outcomes. Conclusion: New clopidogrel users on PPIs are at an increased risk of cardiovascular and gastrointestinal complications compared to those not using PPIs. Although a metabolic effect of PPIs on clopidogrel cannot be excluded, we suggest that the inferior cardiovascular profile of clopidogrel users on PPIs and the occurrence of channelling bias are important factors underlying this observation.