Real-world safety of icosapent ethyl: analysis based on spontaneous reports in FAERS database.

BACKGROUND: The triglyceride-lowering drug, icosapent ethyl (IPE), was granted a new indication for the reduction of atherosclerotic cardiovascular disease risk in 2019. This study aimed to investigate the safety profile of IPE by mining the FDA Adverse Event Reporting System (FAERS) database. METHODS: The reporting odds ratio was used to analyze IPE's adverse events (AEs) based on the FAERS data from July 2012 to December 2022. We described the characteristics of AE reports and evaluated the clinical prioritization of AEs. Then we defined and analyzed nine interested adverse drug reactions (ADRs) in both overall and subgroups, and investigated the times to onset. RESULTS: The findings of our study strengthen the evidence for an increased risk of atrial fibrillation using IPE. IPE alone may not increase the risk of bleeding unless combined with antithrombotic drugs. Similar to statins, IPE alone can increase the risk of musculoskeletal pain, drug-related hepatic disorders, and hyperglycemia, but the risk could not double when IPE was combined with statins. Most ADRs occur in the early stage of treatment. CONCLUSIONS: This study provides a comprehensive real-world safety profile of IPE, which indicates that IPE is well-tolerated.

Prevalence, contemporary trends and associated factors of potentially inappropriate prescription of edoxaban in real-world clinical practice: A subanalysis of the SUNSHINE registry.

AIM: As the direct oral anticoagulant most recently approved in China, data pertaining to clinical edoxaban use are still scarce. This study investigated the prevalence of and contemporary trends in edoxaban prescription among Chinese patients as well as factors associated with its inappropriate use in a multicentre registry of patients treated in real-world clinical practice. METHODS: This real-world, prospective, multicentre and non-interventional study included 1005 inpatients treated with edoxaban. According to National Medical Products Administration and European Heart Rhythm Association guidelines, edoxaban therapy was determined to be appropriate or inappropriate in each case. RESULTS: The median patient age was 70.0 years (interquartile range 61.0-78.0 years) and 46.3% were women. Overall, 456 (45.4%) patients received inappropriate edoxaban therapy, and common issues included an inappropriately low dosage (183, 18.2%) or wrong drug selection (109, 10.8%), high dosage (73, 7.3%), unreasonable off-label use (49, 4.9%), contraindicated medication combinations (27, 2.7%) and incorrect administration timing (16, 1.6%). Several factors, such as age ≥75 years (odds ratio [OR] = 1.921, 95% confidence interval [CI] 1.355-2.723, P < 0.001), weight >60 kg (OR = 2.657, 95%CI 1.970-3.583, P < 0.001), severe renal insufficiency (OR = 1.988, 95% CI 1.043-3.790, P = 0.037), current anaemia (OR = 1.556, 95% CI 1.151-2.102, P = 0.004) and history of bleeding (OR = 2.931, 95% CI 1.605-5.351, P < 0.001) were associated with an increased risk of inappropriate edoxaban therapy, whereas factors associated with cardiovascular specialties, such as admission to a cardiovascular department (OR = 0.637, 95% CI 0.464-0.873, P = 0.005), dronedarone use (OR = 0.065, 95% CI 0.026-0.165, P < 0.001) and amiodarone use (OR = 0.365, 95% CI 0.209-0.637, P < 0.001) decreased this risk. CONCLUSION: In this real-world study, 45.4% of patients received an inappropriate treatment with edoxaban. Multiple clinical characteristics can help identify patients who should receive edoxaban. Further development and implantation of educational activities and management strategies are needed to ensure the correct use of edoxaban.

Prevalence, risk factors, and prediction of inappropriate use of non-vitamin K antagonist oral anticoagulants in elderly Chinese patients with atrial fibrillation: A study protocol.

Background: Atrial fibrillation (AF) is an arrhythmia that is prevalent globally, and its incidence grows exponentially with aging. Non-vitamin K antagonist oral anticoagulants (NOACs) have been developed in recent years, and it challenges the supremacy of warfarin for thromboembolism prophylaxis in AF. Nevertheless, there are limited data specifically evaluating the real-life use of NOACs in elderly patients with AF in China. Methods: This is a national, multicenter, non-interventional, cross-sectional study that enrolls patients with AF aged 75 years and above from 31 institutions across China. Data were collected using the Hospital Information System. The primary outcomes include (1) profiles of NOAC use in the elderly; (2) frequency of inappropriate NOAC use based on guidelines and approved labeling recommendations; (3) exploring potential risk factors related to NOACs inappropriate use; and (4) creating a prediction tool for inappropriate NOACs use. Conclusion: The results of this study reveal the prevalence, risk factors, and corresponding prediction tool of inappropriate NOACs use in older patients with AF in China, as well as provide valuable insights into the clinical application of NOACs in high-risk populations in the real-world setting. Clinical trial registration: www.ClinicalTrials.gov, identifier: NCT05361889.

A Lattice-Matching Strategy for Highly Reversible Copper-Metal Anodes in Aqueous Batteries.

Copper metal is an attractive anode material for aqueous rechargeable batteries due to its high theoretical specific capacity (844 mAh g-1 ), good environmental compatibility and high earth abundance. However, the Cu anodes often suffer from poor deposition/stripping reversibility and nonuniform deposition during the charge/discharge process, degrading the lifetime of aqueous Cu-metal batteries. Herein, a lattice-matching strategy was developed to design high-performance Cu-metal anodes. In such a strategy, Ni substrates that exhibit high lattice matching with Cu were selected to support the Cu anodes. The high lattice matching endows Cu anodes with high deposition/stripping reversibility, low nucleation overpotential as well as a uniform and dense electrodeposition on Ni substrates. Based on the Ni substrate-supported Cu anodes, the full cells paired with lead dioxide cathodes show a stable cycling behavior. This work provides a route for the design of high-performance Cu electrodes in aqueous rechargeable batteries.

Antithrombotic Management for Atrial Fibrillation Patients Undergoing Percutaneous Coronary Intervention or With Acute Coronary Syndrome: An Evidence-Based Update.

Combined antithrombotic regimens for atrial fibrillation (AF) patients with coronary artery disease, particularly for those who have acute coronary syndrome (ACS) and/or are undergoing percutaneous coronary intervention (PCI), presents a great challenge in the real-world clinical scenario. Conventionally, a triple antithrombotic therapy (TAT), which consists of combined oral anticoagulant therapy to prevent systemic embolism or stroke along with dual antiplatelet therapy to prevent coronary arterial thrombosis (CAT), is used. However, TAT has been associated with a significantly increased risk of bleeding. With the emergence of non-vitamin K antagonist oral anticoagulants (NOACs), randomized controlled trials have demonstrated a better risk-to-benefit ratio of dual antithrombotic therapy (DAT) in combination of a NOAC and with a P2Y12 inhibitor than vitamin K antagonist-based TAT. The results of these studies have impacted the recommendations of current international guidelines, which favor a DAT with a NOAC and P2Y12 inhibitor (especially clopidogrel) in this clinical setting. Additionally, aspirin can be administered during the periprocedural period, while the treatment duration of TAT should be as short as possible. In this article, we summarize the up-to-date evidence regarding antithrombotic regimens for AF patients with PCI or ACS, with a specific focus on the optimal approach and critical discussions of key scientific data and future developments for antithrombotic management in these patients.

Appropriate Dosing Regimens of Non-Vitamin K Antagonist Oral Anticoagulants for Treatment of Patients With Non-Valvular Atrial Fibrillation: An Evidence-Based Consideration.

Patients with non-valvular atrial fibrillation (NVAF) exhibit a high risk of stroke, which is associated with high mortality. Thus, stroke prevention is crucial for the overall management of NVAF. Two categories of drugs, vitamin K antagonist warfarin and non-vitamin K antagonist oral anticoagulants (NOACs), are clinically used to prevent NVAF-related stroke. In some circumstances, NOACs are superior to warfarin. However, NOACs selection for NVAF patients is affected by many factors, including individual patient characteristics, comorbidities, risk factors, or laboratory variables. This article summarizes the discrepancy in NOACs management with emphasis on the dosing regimens and influencing factors, such as stroke risk, age, body weight, renal function, gastrointestinal bleeding (GIB) risk, and combination of antiplatelet therapy, in order to identify individual groups with particular clinical characteristics who may obtain more benefit from a certain dosing regimen of NOACs. Determination of a particular subset of patient populations for the appropriate dose regimen of NOACs will help to achieve desired clinical outcomes. Furthermore, to compensate clinical evidence, we should place more emphasis on the findings of current clinical trials and supplement real-world data.

Antituberculosis drug prescribing for inpatients in a national tuberculosis hospital in China, 2011-2015.

OBJECTIVES: This study aimed to describe trends in antituberculosis drug prescribing for inpatients from 2011-2015 in a Chinese national tuberculosis (TB) hospital. METHODS: This retrospective study, performed in March 2016, reviewed the medical records of all inpatients from Beijing Chest Hospital diagnosed with TB between 2011-2015. Medication used for TB treatment during the inpatient period was recorded. RESULTS: A total of 11465 inpatients were enrolled in the study. The most frequently prescribed drug for inpatients was isoniazid (71.2%; 8164/11465), followed by ethambutol (67.5%; 7738/11465), pyrazinamide (59.7%; 6839/11465) and rifampicin (40.0%; 4589/11465). In addition, amikacin (16.5%; 1889/11465), levofloxacin (33.0%; 3789/11465), para-aminosalicylic acid (12.4%; 1422/11465) and clarithromycin (3.5%; 406/11465) were the most common drugs used in the treatment of inpatients for Group II, III, IV and V drugs, respectively. A significant increasing trend in prescribing was found for rifampicin, pyrazinamide, capreomycin, moxifloxacin, prothionamide, para-aminosalicylic acid, cycloserine, clofazimine and linezolid, respectively, whilst there was a significant decreasing trend in the rate of prescribing of ethambutol, amikacin, levofloxacin, amoxicillin/clavulanic acid and clarithromycin during the 5-year study period (Ptrend<0.01). CONCLUSIONS: These data demonstrate that prescription of anti-TB drugs varied greatly across clinical diagnostic categories, treatment history and drug susceptibility profiles of TB patients. The World Health Organization (WHO)-endorsed standard regimen should be more extensively employed under conditions where drug susceptibility testing is unavailable in order to guide clinicians to formulate a suitable treatment regimen for TB patients.

Factors influencing medication knowledge and beliefs on warfarin adherence among patients with atrial fibrillation in China.

OBJECTIVES: Warfarin is often used for ischemic stroke prevention in patients with atrial fibrillation (AF), but the factors affecting patient adherence to warfarin therapy have not been fully understood. METHODS: A cross-sectional survey was conducted in AF patients undergoing warfarin therapy at least 6 months prior to the study. The clinical data collected using questionnaires by phone interviews included the following: 1) self-reported adherence measured by the Morisky Medication Adherence Scale-8©; 2) beliefs about medicines surveyed by Beliefs about Medicines Questionnaire (BMQ); and 3) drug knowledge as measured by the Warfarin Related Knowledge Test (WRKT). Demographic and clinical factors associated with warfarin adherence were identified using a logistic regression model. RESULTS: Two hundred eighty-eight patients completed the survey and 93 (32.3%) of them were classified as nonadherent (Morisky Medication Adherence Scale-8 score <6). Major factors predicting warfarin adherence included age, cardiovascular disorders, WRKT, and BMQ; WRKT and BMQ were independently correlated with adherence to warfarin therapy by multivariate logistic regression analysis. Adherents were more likely to have greater knowledge scores and stronger beliefs in the necessity of their specific medications ([odds ratio {OR} =1.81, 95% confidence interval {CI} =1.51-2.15] and [OR =1.17, 95% CI =1.06-1.29], respectively). Patients with greater concerns about adverse reactions and more negative views of general harm were more likely to be nonadherent ([OR =0.76, 95% CI =0.69-0.84] and [OR =0.82, 95% CI =0.73-0.92], respectively). CONCLUSION: BMK and WRKT are related with patient behavior toward warfarin adherence. BMQ can be applied to identify patients at increased risk of nonadherence.

A prospective study investigating the causes of warfarin under-utilization in Chinese patients.

Background Warfarin is efficacious for ischemic stroke prevention in intermediate- to high-risk patients with atrial fibrillation; thus, warfarin is the recommended treatment according to evidence-based guidelines. Objective This prospective study evaluated the reasons for under-utilization of warfarin in Chinese patients with non-valvular atrial fibrillation (NVAF). Setting The People's Hospital of Henan Province of Zhengzhou City, which is a 3900-bed tertiary-care teaching institution. Methods We extracted data from an existing patient database. Patients at risk for thromboembolism were categorized based on CHA2DS2-VASc [congestive heart failure, hypertension, age ≥75 (doubled), diabetes, prior stroke (doubled), vascular disease, age 65-74 years, and sex category (female)] scores. Main outcome measure The percent of warfarin utilization was estimated in recruited patients. Any demographic and clinical factors associated with warfarin under-utilization were identified using a logistic regression model. Results Among the patient sample (n = 612), 569 patients had a CHA2DS2-VASc score of ≥1. At presentation, warfarin under-utilization was estimated to be 27.1 %. Only 120 patients (25.1 %) considered to be at the highest risk were prescribed warfarin. Binary logistic regression analysis indicated that previous stroke, age ≥75 years, and anti-platelet therapy were associated with warfarin under-utilization. Conclusion Patients with CHA2DS2-VASc scores ≥1 who were admitted with NVAF were under prescribed warfarin, and 138 patients were not treated with either warfarin or other antithrombotic therapies. In conclusion, a more aggressive approach for stroke prevention in NVAF patients is required.

Characterization of novel astragaloside malonates from Radix Astragali by HPLC with ESI quadrupole TOF MS.

A structurally identified new compound named malonylastragaloside I was isolated and obtained from Radix Astragali. This novel compound was found to be unstable especially under high temperature and pH value. Using sonication extraction, addition of formic acid, and an efficient medium pressure ODS C(18) column chromatography method, a high yield of 40 mg of this compound was obtained from 150 g of powdered crude herbal medicine. Malonylastragaloside I was structurally characterized by NMR and ESI quadrupole TOF MS. With the strategy of target precursor ions scan, a total of 22 astragalosides including 8 astragaloside malonates were screened and characterized from the methanolic extract of Radix Astragali by HPLC-Q-TOF/MS. The eight astragaloside malonates were found in both Astragalus membranaceus var. mongholicus and A. membranaceus. The results provided a real profile of various triterpene saponins in Radix Astragali. It is a first report regarding isolation and characterization of astragaloside malonates in Astragalus species.

Anti-diabetic agents from natural products--an update from 2004 to 2009.

Diabetes mellitus (DM), the third killer of the mankind health along with cancer, cardiovascular and cerebrovascular diseases, is one of the most challenging diseases facing health care professionals today. The World Health Organization (WHO) has declared that a DM epidemic is underway. Primary DM and its complications are costly to manage, not only for affected individuals, but also for healthcare systems around the world. Screening of anti-diabetic agents has been extensively investigated in the past decades. Natural products (NPs) have served as a major source of drugs for centuries, and about half of the pharmaceuticals in use today are derived from natural substances. Many natural products especially plants-derived medicines have been recommended for the treatment of DM. The present paper reviews NPs appeared in the literature with potential for DM and also identifies the research needs in this area. It mainly covers the time period from January 2004 to October 2008. The current review is divided into three major sections based on classification of the natural materials involved. The first part focuses on known and some new chemical entities isolated mainly from medicinal plants possessing anti-diabetic properties, including saponins, flavonoids, alkaloids, anthraquinones, terpenes, coumarins, phenolics, polysaccharides, and some other compounds. The second part summarizes crude extract of medicinal plants which are commonly used in the traditional Chinese medical system and have been demonstrated experimental or/and clinical anti-diabetic effectiveness, mainly including Leguminosae, Cucurbitaceae, Araliaceae, Liliaceae, Chenopodiaceae, Solanaceae, Compositae, Campanulaceae, Cornaceae, Rhamnaceae, Scrophulariaceae, Euphorbiaceae, Ginkgoceae, Gramineae, Myrtaceae, Sterculiaceae, Annonaceae, Labiatae, Crassulaceae, and Miscellaneous. The third part lists some compound formulae consisting of extracts of several plants that have been reported as beneficial for the treatment of DM, major involving Xiaokeling tablet, Ba-Wei-Di-Huang-Wan and Formula 1.

[Simultaneous assay of four isoflavonoids in Astragali Radix by QAMS].

Based on the complexity of the chemical constitutions in traditional Chinese medicines (TCMs), multi-components analysis used for the quality control of TCMs is more scientific and reasonable. However, routine quality control of TCMs by multi-components analysis is limited for the shortage of various chemical reference substances. Herein, the method of quantitative analysis of multi-components by single marker (QAMS) was validated and used to simultaneously determine calycosin-7-O-beta-D-glucopyranoside, ononin, calycosin, formononetin in Radix Astragali. Using formononetin as the internal reference substance, the relative correction factors (RCFs) of the other three isoflavonoids were calculated by HPLC-DAD with good reproducibility in different instruments and chromatographic columns. The other three isoflavonoids in 34 batches of samples were simultaneously calculated according to their RCFs. The results of QAMS method were not significantly different from that of external standard method (RSD < 3.5%). It is accurate and feasible to evaluate the quality of Radix Astragali by QAMS.