Temporal trends in use of antisecretory agents among patients administered clopidogrel-based dual antiplatelet therapy after percutaneous coronary intervention.

BACKGROUND: Antisecretory drugs are commonly prescribed with clopidogrel-based dual antiplatelet therapy (DAPT) to prevent gastrointestinal bleeding in high-risk patients after percutaneous coronary intervention (PCI). However, omeprazole and esomeprazole (inhibiting proton pump inhibitors [PPIs]) may increase cardiovascular event rates on co-administration with clopidogrel. This study aimed to examine trends in the use of antisecretory agents in patients administered clopidogrel-based DAPT and the concomitant use of clopidogrel and inhibiting PPIs. METHODS: We used National Inpatient Sample data compiled by the Health Insurance Review & Assessment Service from 2009 to 2020. Further, we identified patients who were prescribed clopidogrel-based DAPT after PCI and investigated the concomitant use of antisecretory agents with clopidogrel. To verify the annual trend of drug utilization, we used the Cochran-Armitage trend test. RESULTS: From 2009 to 2020, the percentage of H2 receptor antagonist users decreased steadily (from 82.5% in 2009 to 25.3% in 2020); instead, the percentage of PPI users increased (from 23.7% in 2009 to 82.0% in 2020). The use of inhibiting PPI also increased (from 4.2% in 2009 to 30.7% in 2020). Potassium competitive acid blockers (P-CABs) were rarely used before 2019; however, in 2020, it accounted for 7.8% of the antisecretory users. CONCLUSIONS: Our study demonstrates that the use of inhibiting PPIs increased steadily in patients administered clopidogrel-based DAPT therapy. This is a major concern since the concomitant use of inhibiting PPIs with clopidogrel could increase the risk of cardiovascular events.

Risk factors and management of gastrointestinal bleeding in patients with or without antiplatelet and anticoagulation therapy: a multicenter real-world prospective study.

BACKGROUND: Antiplatelet and anticoagulation drugs complicate acute gastrointestinal bleeding (GIB) patients. Limited data about the risk factors and patient management has been presented. This study explored the association between previous antiplatelet or anticoagulant drug usage and clinical outcomes in GIB patients to improve awareness further and optimize treatment. METHODS: We conducted a multicenter, non-interventional, real-world prospective study in 106 hospitals in 23 provinces in China. GIB patients confirmed in the emergency department were included and were grouped according to previous drug histories. Univariate analysis, multivariate logistic regression, and multivariate stratification models were performed separately to investigate the associations. RESULTS: A total of 2299 patients (57.23 ± 17.21 years old, 68.3% male) were included, of whom 20.1% and 2.9% received antiplatelet and anticoagulation therapy, respectively. The all-cause 28-day mortality rates in patients without antiplatelet or anticoagulants, patients undergoing antiplatelet treatment, and patients with anticoagulation therapy were 2.8%, 4.6%, and 10.5%, respectively. After adjusting for confounding factors, both antiplatelet [odd ratio (OR), 2.92; 95% confidence interval (CI), 1.48-5.76; p = 0.002] and anticoagulation therapy (OR, 8.87; 95% CI, 3.02-26.02; p < 0.001) were associated with higher 28-day mortality. In the subgroup analysis, blood transfusion, especially red blood cell transfusion, in patients undergoing antiplatelet and anticoagulation therapy was associated with a decreased death risk. CONCLUSION: We confirmed an association between concurrent antiplatelet or anticoagulation therapy in GIB patients and elevated 28-day mortality. Blood transfusions could improve poor outcomes in such patients.

Reversal or Repletion Treatment Strategies and Outcomes of Patients With Major Bleeding Events Managed in the Emergency Department: Large Real-Life Investigation in the Northwestern Healthcare District of Tuscany.

OBJECTIVE: To verify the incidence of bleeding events in patients on ongoing anticoagulant treatment in the real world and compare the results of different reversal or repletion strategies currently available for pharmacological treatment. METHODS: Patients managed in the emergency department (ED) with major bleeding events, on ongoing anticoagulation were stratified according to bleeding site and reversal or repletion therapy with andexanet alfa (ADX), idarucizumab (IDA), prothrombin complex concentrate (PCC), and vitamin K (Vit-K). ENDPOINT: Death at 30 days was compared in the subgroups with cerebral hemorrhage (CH) and gastrointestinal (GI) bleeding. RESULTS: Of the 809,397 visits in the years 2022-2023 at 6 EDs in the northwestern health district of Tuscany, 5372 patients with bleeding events were considered; 3740 were excluded due to minor bleeding or propensity score matching. Of the remaining 1632 patients with major bleeding, 548 on ongoing anticoagulation were enrolled; 334 received reversal or repletion agents. Patients with CH (n = 176) and GI bleeding (n = 108) represented the primary analysis cohorts in the study's strategic treatment assessment. Overall, 30-day survival of patients on ongoing aFXa treatment receiving on-label ADX versus off-label PCC showed a relative increase of 71%, while 30-day survival of patients on ongoing aFII receiving on-label IDA versus off-label PCC showed a relative increase of 30%; no substantial difference was found when comparing on-label PCC combined with Vit-K versus off-label Vit-K alone. Indeed, patients undergoing on-label ADX or IDA showed a statistically significant difference over off-label PCC (ADX vs. PCC: n = 15, events = 4, mean ± SD 82.50 ± 18.9, vs. 49, 13, 98.82 ± 27, respectively; analysis of variance [ANOVA] variance 8627; P < 0.001; posthoc test diff 32, 95% confidence interval: 28-35; P < 001; IDA vs. PCC: 20, 5, 32.29 ± 15.0 vs. 2, 1, 28.00 ± 0.0, respectively; ANOVA 1484; P < 0.001; posthoc test -29, -29 -29, respectively; P = n.d.). On-label PCC combined with Vit-K showed overall a slight statistically significant difference versus off-label Vit-K alone (52, 16, 100.58 ± 22.6 vs. 53, 11, 154.62 ± 29.8, respectively; ANOVA 310; P < 0.02; posthoc test 4, 0.7-7.2, respectively; P < 0.02). Data were confirmed in the group of patients with CH (ADX vs. PCC: n = 13, events = 3, mean ± SD 91.55 ± 18.6 vs. 78, 21, 108.91 ± 20.9, respectively; ANOVA variance 10,091, F = 261; P < 0.001; posthoc difference test 36, 95% confidence interval: 30-41; P < 0.001; IDA vs. PCC: 10, 2, 4.50 ± 2.5 vs. 78, 21, 108.91 ± 20.9, respectively; ANOVA 16,876,303, respectively; P < 0.001; posthoc test 41, 34-47, respectively; P < 0.001). On-label PCC combined with Vit-K showed an overall slight statistically significant difference compared with off-label Vit-K alone (P < 0.01 and P < 0.001 in the subgroups of CH and GI bleeding). CONCLUSIONS: Patients undergoing specific reversal therapy with on-label ADX or IDA, when treated with aFXa or aFII anticoagulants, respectively, showed statistically elevated differences in 30-day death compared with off-label repletion therapy with PCC. Overall, 30-day survival of patients on ongoing aFXa or aFII receiving on-label reversal therapy with ADX or IDA compared with off-label PCC repletion agents showed an increase of 71% and 30%, respectively.

Guideline versus clinician recommended duration of dual antiplatelet therapy following acute coronary syndrome (ANZACS-QI 78).

AIM: The recommended duration of dual anti-platelet therapy (DAPT) following acute coronary syndrome (ACS) for patients without atrial fibrillation varies from 1 month to 1 year depending on the balance of risks of ischaemia and major bleeding. Patients on DAPT with a high risk of gastrointestinal bleeding are also recommended to receive a proton pump inhibitor (PPI). Our aim was to audit current practice against the 2020 European Society of Cardiology (ESC) guideline recommendations. METHODS: One hundred consecutive ACS patients treated with percutaneous coronary intervention discharged from Middlemore Hospital and without atrial fibrillation in the first quarter of 2023 were studied. ANZACS-QI ischaemic (I) and bleeding (B) risk scores were calculated, with patients categorised in four groups based on ESC recommendations-low I/low B risk, low I/high B, high I/low B and high I/high B. Guideline and clinician recommended duration of DAPT and prescription of PPI were compared. RESULTS: All patients were planned for DAPT at discharge and 91% a PPI. Up to four out of five ACS patients could have been planned for shorter DAPT durations based on the ESC guideline recommendations. Over half of included patients (53%) had a high bleeding risk, yet 85% of these patients received 12 months of DAPT despite ESC recommendations of 1-3 months. CONCLUSIONS: There was a divergence between clinical practice and the recommendations of the 2020 ESC guidelines. We discuss these results in relation to the updated August 2023 ESC guidelines, which have reaffirmed a 12-month duration of DAPT as the default position.

Widespread use of proton pump inhibitors or potassium-competitive acid blocker has changed the status of gastrointestinal bleeding in patients with ischemic heart disease: real-world data from high volume centers.

BACKGROUND: Although proton pump inhibitors (PPIs) or potassium-competitive acid blocker (PCAB) are useful in peptic ulcer prevention, their efficacy in preventing other gastrointestinal bleeding remains unclear. This study aimed to identify the status of gastrointestinal bleeding in the modern era when PPIs are widely used. METHODS: This study included patients who underwent percutaneous coronary intervention (PCI) between 2018 and 2019 at two high-volume centers. Patients were categorized based on whether they experienced gastrointestinal bleeding within 2 years of PCI into groups A (patients who experienced gastrointestinal bleeding within 2 years after PCI) and B (patients who did not experience gastrointestinal bleeding). RESULTS: Groups A and B included 21 (4.1%) and 494 (95.9%) patients, respectively (a total of 515 patients). Age at the initial PCI (77.8±2.4 and 72.0±0.5 years in groups A and B, respectively; p = 0.02), weight (53.8±3.2 and 61.8±0.7 kg in groups A and B, respectively; p = 0.01), and concomitant warfarin use (14.3% and 2.0% in groups A and B, respectively; p = 0.0005) were significantly different between the groups. The high bleeding risk rate (90.5% and 47.6% in groups A and B, respectively; p = 0.0001) was significantly different between the groups. A total of 95.9% of patients were taking PPIs or PCAB without significant differences between the groups. However, only one patient, who was taking steroids, had a gastric ulcer during PCAB treatment. CONCLUSIONS: Acid-related upper gastrointestinal bleeding is largely controlled by PPIs in post-PCI patients. Furthermore, the risk factors for non-acid-related bleeding include older age, lower weight, and concomitant warfarin use.

Intra-abdominal hematomas and identifiable risk factors in patients receiving subcutaneous enoxaparin.

BACKGROUND: Low molecular weight heparin has proven to be safe and effective but is not without potential risks such as spontaneous bleeding in the abdominal cavity. There is limited evidence evaluating the true incidence of this potential risk and the available literature is primarily via case reports. CASE SUMMARY: The purpose of this study was to identify the incidence and risk factors associated with enoxaparin use (prophylaxis or treatment) abdominal hematomas in a 350-bed community hospital during an 8-month time period. A total of 44 patients were identified as clinically significant bleeds receiving enoxaparin treatment or prophylactic therapy. Ultimately, 25 patients were excluded from the analysis due to an external cause of the abdominal hematoma or a temporal mismatch in enoxaparin administration and hematoma formation. After exclusion, there were a total of 19 patients that were assessed for the risk factors such as age, gender, renal function, and weight. After evaluation of risks, over half of the patients developing a clinically significant bleed were considered elderly (>65 years of age) and impaired renal function with a creatinine clearance of 60ml/min or less. CONCLUSION: Patients at risk for an enoxaparin associated hematoma include female patients with a CrCl <60ml/min and/or BMI >30 kg/m2 receiving enoxaparin treatment dosing.

Gastrointestinal bleeding in elderly patients with atrial fibrillation: prespecified All Nippon Atrial Fibrillation in the Elderly (ANAFIE) Registry subgroup analysis.

Gastrointestinal (GI) bleeding control is critical in elderly patients with atrial fibrillation (AF) receiving oral anticoagulants (OAC). This subgroup analysis aimed to clarify the actual state and significance of GI bleeding in elderly non-valvular AF (NVAF) patients. We evaluated the incidence and risk factors of GI bleeding during the 2-year follow-up and examined the GI bleeding impact on mortality. Of the 32,275 patients in the ANAFIE Registry, 1139 patients (3.5%) experienced GI bleeding (incidence rate, 1.92 events per 100 person-years; mean follow-up, 1.88 years); 339 upper and 760 lower GI bleeding events occurred. GI bleeding risk factors included age ≥ 85 years, body mass index ≥ 25.0 kg/m2, prior major bleeding, hyperuricaemia, heart failure, P-glycoprotein inhibitor use, GI disease, and polypharmacy (≥ 5 drugs). No significant differences in GI bleeding risk were found between direct OAC (DOAC) vs warfarin users (adjusted hazard ratios [95% confidence interval], 1.01 [0.88-1.15]). The 1-year post-GI bleeding mortality rate was numerically higher in patients with upper (19.6%) than lower GI bleeding (8.9%). In elderly Japanese NVAF patients, this large-scale study found no significant difference in GI bleeding risk between DOAC vs. warfarin users or 1-year mortality after upper or lower GI bleeding.

Proton Pump Inhibitor Associated Multiple Gastric Hyperplastic Polyps With Uncontrollable Bleeding: A Case Report.

BACKGROUND/AIM: The long-term use of proton pump inhibitors (PPIs) has been reported to be strongly associated with the development of fundic gland polyps (FGPs). Conversely, a few cases of gastric hyperplastic polyps (GHPs) associated with PPI use have been reported. We experienced a case of PPI-associated multiple GHPs with uncontrollable bleeding. CASE REPORT: A 64 year old man with a history of rheumatoid arthritis presented to the hospital with complaints of vertigo and black stools. Blood tests revealed anemia and hypoproteinemia. Esophagogastroduodenoscopy (EGD) showed blood and black residue accumulated in the stomach. The source of the bleeding was multiple hyperplastic polyps. Bleeding could be stopped even with fasting, and total blood transfusions amounted to 28 units of RBCs were required in 18 days. After the cessation of PPI, EGD showed that the polyps had almost disappeared. Pathological diagnosis of resected polyp was hyperplastic polyp, which was characterized by capillary hyperplasia and edema. Gastrin receptors were over-expressed in the foveolar epithelium and not in the capillaries. Methotrexate (MTX)-induced portal hypertensive gastroenteropathy was revealed during follow-up. We consider that the effect of portal hypertension may have caused the capillary hyperplasia. CONCLUSION: Although PPI-related polyps are usually fundic gland polyps and do not cause life-threatening adverse events, we experienced PPI-related GHPs in which hemostasis was difficult to control.

Impact of large scale, multicomponent intervention to reduce proton pump inhibitor overuse in integrated healthcare system: difference-in-difference study.

OBJECTIVE: To determine how a large scale, multicomponent, pharmacy based intervention to reduce proton pump inhibitor (PPI) overuse affected prescribing patterns, healthcare utilization, and clinical outcomes. DESIGN: Difference-in-difference study. SETTING: US Veterans Affairs Healthcare System, in which one regional network implemented the overuse intervention and all 17 others served as controls. PARTICIPANTS: All individuals receiving primary care from 2009 to 2019. INTERVENTION: Limits on PPI refills for patients without a documented indication for long term use, voiding of PPI prescriptions not recently filled, facilitated electronic prescribing of H2 receptor antagonists, and education for patients and clinicians. MAIN OUTCOME MEASURES: The primary outcome was the percentage of patients who filled a PPI prescription per 6 months. Secondary outcomes included percentage of days PPI gastroprotection was prescribed in patients at high risk for upper gastrointestinal bleeding, percentage of patients who filled either a PPI or H2 receptor antagonist prescription, hospital admission for acid peptic disease in older adults appropriate for PPI gastroprotection, primary care visits for an upper gastrointestinal diagnosis, upper endoscopies, and PPI associated clinical conditions. RESULTS: The number of patients analyzed per interval ranged from 192 607 to 250 349 in intervention sites and from 3 775 953 to 4 360 868 in control sites, with 26% of patients receiving PPIs before the intervention. The intervention was associated with an absolute reduction of 7.3% (95% confidence interval -7.6% to -7.0%) in patients who filled PPI prescriptions, an absolute reduction of 11.3% (-12.0% to -10.5%) in PPI use among patients appropriate for gastroprotection, and an absolute reduction of 5.72% (-6.08% to -5.36%) in patients who filled a PPI or H2 receptor antagonist prescription. No increases were seen in primary care visits for upper gastrointestinal diagnoses, upper endoscopies, or hospital admissions for acid peptic disease in older patients appropriate for gastroprotection. No clinically significant changes were seen in any PPI associated clinical conditions. CONCLUSIONS: The multicomponent intervention was associated with reduced PPI use overall but also in patients appropriate for gastroprotection, with minimal evidence of either clinical benefits or harms.

Active surveillance pharmacovigilance for Clostridioides difficile infection and gastrointestinal bleeding: an analytic framework based on case-control studies.

BACKGROUND: Active surveillance pharmacovigilance is an emerging approach to identify medications with unanticipated effects. We previously developed a framework called pharmacopeia-wide association studies (PharmWAS) that limits false positive medication associations through high-dimensional confounding adjustment and set enrichment. We aimed to assess the transportability and generalizability of the PharmWAS framework by using medical claims data to reproduce known medication associations with Clostridioides difficile infection (CDI) or gastrointestinal bleeding (GIB). METHODS: We conducted case-control studies using Optum's de-identified Clinformatics Data Mart Database of individuals enrolled in large commercial and Medicare Advantage health plans in the United States. Individuals with CDI (from 2010 to 2015) or GIB (from 2010 to 2021) were matched to controls by age and sex. We identified all medications utilized prior to diagnosis and analysed the association of each with CDI or GIB using conditional logistic regression adjusted for risk factors for the outcome and a high-dimensional propensity score. FINDINGS: For the CDI study, we identified 55,137 cases, 220,543 controls, and 290 medications to analyse. Antibiotics with Gram-negative spectrum, including ciprofloxacin (aOR 2.83), ceftriaxone (aOR 2.65), and levofloxacin (aOR 1.60), were strongly associated. For the GIB study, we identified 450,315 cases, 1,801,260 controls, and 354 medications to analyse. Antiplatelets, anticoagulants, and non-steroidal anti-inflammatory drugs, including ticagrelor (aOR 2.81), naproxen (aOR 1.87), and rivaroxaban (aOR 1.31), were strongly associated. INTERPRETATION: These studies demonstrate the generalizability and transportability of the PharmWAS pharmacovigilance framework. With additional validation, PharmWAS could complement traditional passive surveillance systems to identify medications that unexpectedly provoke or prevent high-impact conditions. FUNDING: U.S. National Institute of Diabetes and Digestive and Kidney Diseases.

Transient pulmonary and gastric bleeding after iopamidol administration in a patient with marginal zone lymphoma: a case report.

BACKGROUND: Iopamidol is a non-ionic, water-soluble iodine contrast agent that is considered safe for intravenous or intra-arterial administration and is widely used both in the general population and in patients undergoing oncological treatment. While adverse reactions to iopamidol have been documented, to date, no pulmonary and gastric hemorrhages induced by iopamidol have been reported in oncology patients. We report the first case of this complication. CASE PRESENTATION: We report the case of a 60-year-old woman with marginal zone lymphoma who was receiving antineoplastic therapy. As part of the investigation for the condition, she underwent chest enhancement CT with iopamidol. Shortly thereafter(within five minutes), she experienced hemoptysis and hematemesis. She was intubated and admitted to the intensive care unit. Pre- and post-contrast images demonstrated the course of the hemorrhage. Flexible bronchoscopy and gastroscopy on the following day showed no active bleeding, and the patient recovered completely after antiallergy treatment. We speculate that contrast-induced hypersensitivity was the most likely cause of the transient pulmonary and gastric bleeding. CONCLUSION: Although rare, the complications of iopamidol, which may cause allergic reactions in the lungs and stomach, should be considered.

Safety profile of rivaroxaban in first-time users treated for venous thromboembolism in four European countries.

BACKGROUND: The European rivaroxaban post-authorization safety study evaluated bleeding risk among patients initiated on rivaroxaban or vitamin K antagonists for the treatment and secondary prevention of venous thromboembolism in routine clinical practice. METHODS: Cohorts were created using electronic healthcare databases from the UK, the Netherlands, Germany and Sweden. Patients with a first prescription of rivaroxaban or vitamin K antagonist during the period from December 2011 (in the UK, January 2012) to December 2017 (in Germany, December 2016) for venous thromboembolism indication, with no record of atrial fibrillation or recent cancer history, were observed until the occurrence of each safety outcome (hospitalization for intracranial, gastrointestinal, urogenital or other bleeding), death or study end (December 2018; in Germany, December 2017). Crude incidence rates of each outcome per 100 person-years were computed. RESULTS: Overall, 44 737 rivaroxaban and 45 842 vitamin K antagonist patients were enrolled, mean age, 59.9-63.8 years. Incidence rates were similar between rivaroxaban and vitamin K antagonist users with some exceptions, including higher incidence rates for gastrointestinal bleeding in rivaroxaban users than in vitamin K antagonist users. Among rivaroxaban users, mortality and bleeding risk generally increased with age, renal impairment and diabetes. CONCLUSIONS: This study provides further data from routine clinical practice that broadly support safety profile of rivaroxaban for VTE indication and complement findings from previous randomized clinical trials.

Pharmacogenetic and clinical risk factors for bevacizumab-related gastrointestinal hemorrhage in prostate cancer patients treated on CALGB 90401 (Alliance).

The objective of this study was to discover clinical and pharmacogenetic factors associated with bevacizumab-related gastrointestinal hemorrhage in Cancer and Leukemia Group B (Alliance) 90401. Patients with metastatic castration-resistant prostate cancer received docetaxel and prednisone ± bevacizumab. Patients were genotyped using Illumina HumanHap610-Quad and assessed using cause-specific risk for association between single nucleotide polymorphisms (SNPs) and gastrointestinal hemorrhage. In 1008 patients, grade 2 or higher gastrointestinal hemorrhage occurred in 9.5% and 3.8% of bevacizumab (n = 503) and placebo (n = 505) treated patients, respectively. Bevacizumab (P < 0.001) and age (P = 0.002) were associated with gastrointestinal hemorrhage. In 616 genetically estimated Europeans (n = 314 bevacizumab and n = 302 placebo treated patients), grade 2 or higher gastrointestinal hemorrhage occurred in 9.6% and 2.0% of patients, respectively. One SNP (rs1478947; HR 6.26; 95% CI 3.19-12.28; P = 9.40 × 10-8) surpassed Bonferroni-corrected significance. Grade 2 or higher gastrointestinal hemorrhage rate was 33.3% and 6.2% in bevacizumab-treated patients with the AA/AG and GG genotypes, versus 2.9% and 1.9% in the placebo arm, respectively. Prospective validation of these findings and functional analyses are needed to better understand the genetic contribution to treatment-related gastrointestinal hemorrhage.

Patterns of Comorbidities and Prescribing and Dispensing of Non-steroidal Anti-inflammatory Drugs (NSAIDs) Among Patients with Osteoarthritis in the USA: Real-World Study.

BACKGROUND: Osteoarthritis (OA) is a major cause of chronic pain. Non-steroidal anti-inflammatory drugs (NSAIDs) are analgesics commonly used for musculoskeletal pain; however, NSAIDs can increase the risk of certain adverse events, such as gastrointestinal bleeding, edema, heart failure, and hypertension. OBJECTIVE: The objective of this study was to characterize existing comorbidities among patients with OA. For patients with OA with and without a coexisting medical condition of interest (CMCOI), we estimated the prevalence of prescribing and dispensing NSAIDs pre-OA and post-OA diagnosis. METHODS: Data from three large administrative claims databases were used to construct an OA retrospective cohort. Databases leveraged were IBM MarketScan Medicare Supplemental Database (MDCR), IBM MarketScan Commercial Database (CCAE), and Optum's de-identified Clinformatics® Data Mart Database (Optum CDM). The OA study population was defined to be those patients who had an OA diagnosis from an inpatient or outpatient visit with at least 365 days of prior observation time in the database during January 2000 through May 2021. Asthma, cardiovascular disorders, renal impairment, and gastrointestinal bleeding risks were the CMCOI of interest. Patients with OA were then classified as having or not having evidence of a CMCOI. For both groups, NSAID dispensing patterns pre-OA and post-OA diagnosis were identified. Descriptive analysis was performed within the Observational Health Data Sciences and Informatics framework. RESULTS: In each database, the proportion of the OA population with at least one CMCOI was nearly 50% or more (48.0% CCAE; 74.4% MDCR; 68.6% Optum CDM). Cardiovascular disease was the most commonly observed CMCOI in each database, and in two databases, nearly one in four patients with OA had two or more CMCOI (23.2% MDCR; 22.6% Optum CDM). Among the OA population with CMCOI, NSAID utilization post-OA diagnosis ranged from 33.0 to 46.2%. Following diagnosis of OA, an increase in the prescribing and dispensing of NSAIDs was observed in all databases, regardless of patient CMCOI presence. CONCLUSIONS: This study provides real-world evidence of the pattern of prescribing and dispensing of NSAIDs among patients with OA with and without CMCOI, which indicates that at least half of patients with OA in the USA have a coexisting condition. These conditions may increase the risk of side effects commonly associated with NSAIDs. Yet, at least 32% of these patients were prescribed and dispensed NSAIDs. These data support the importance of shared decision making between healthcare professionals and patients when considering NSAIDs for the treatment of OA in patients with NSAID-relevant coexisting medical conditions.

Major bleeding in patients with atrial fibrillation treated with apixaban versus warfarin in combination with amiodarone: nationwide cohort study.

BACKGROUND: Amiodarone is an established treatment for atrial fibrillation (AF) but might interfere with the metabolism of apixaban or warfarin. Therefore, the aim was to investigate the occurrence of major bleeding among patients with AF treated with amiodarone in combination with apixaban or warfarin. METHODS: Retrospective observational study using Swedish health registers. All patients with AF in the National Patient Register and the National Dispensed Drug Register with concomitant use of amiodarone and warfarin or apixaban between 1 June 2013 and 31 December 2018 were included. Propensity score matching was performed, and matched cohorts were compared using Cox proportional HRs. The primary outcome was major bleeding resulting in hospitalisation based on International Classification of Diseases (ICD)-10 codes. Secondary outcomes included intracranial bleeding, gastrointestinal bleeding and other bleeding. Exploratory outcomes included ischaemic stroke/systemic embolism and all-cause/cardiovascular (CV) mortality. RESULTS: A total of 12 103 patients met the inclusion criteria and 8686 patients were included after propensity score matching. Rates of major bleeding were similar in the apixaban (4.3/100 patient-years) and warfarin cohort (4.5/100 patient-years) (HR: 1.03; 95% CI: 0.76 to 1.39) during median follow-up of 4.4 months. Similar findings were observed for secondary outcomes including gastrointestinal bleeding and other bleeding, and exploratory outcomes including ischaemic stroke/systemic embolism and all-cause/CV mortality. CONCLUSIONS: Among patients treated with amiodarone in combination with apixaban or warfarin, major bleeding and thromboembolic events were rare and with no significant difference between the treatment groups. EUPAS REGISTRY NUMBER: EUPAS43681.

Management of Anticoagulant and Antiplatelet Agents in Acute Gastrointestinal Bleeding and Prevention of Gastrointestinal Bleeding.

Managing gastrointestinal bleeding in patients using antithrombotic agents remains challenging in clinical practice. This review article provides a comprehensive and evidence-based approach to managing acute antithrombotic-related gastrointestinal bleeding, focusing on the triage of patients, appropriate resuscitation, and timely endoscopy. The latest clinical practice guidelines are highlighted to guide decisions concerning the use of reversal agents, temporary interruption, and resumption of antithrombotic drugs. Additionally, preventive measures are discussed to lower the risk of future bleeding and minimize complications among patients prescribed antithrombotic drugs.