Inappropriate Use of Aspirin in Real-Life Cardiology Practice: Results from the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study (ASSOS) Study.

BACKGROUND: Indications and appropriateness of aspirin use have not been well investigated in Turkey. AIMS: To investigate the prescription patterns and appropriateness of aspirin in a real-world clinical setting. STUDY DESIGN: Cross-sectional study. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study (ASSOS) is a cross-sectional and multicenter study that included 5007 consecutive patients aged 18 or over who presented to 30 different cardiology outpatient clinics from 14 cities throughout Turkey. Only patients using aspirin (80-325 mg) were included. The study population was divided into 2 groups regarding the use of aspirin: primary prevention (PP) group and secondary prevention (SP) group. The indication of aspirin use was evaluated following the 2016 European Society of Cardiology (ESC) and the 2016 United States Preventative Services Task Force (USPTF) guidelines in the PP group. RESULTS: A total of 5007 patients (mean age 62.15 ± 11.05, 39% female) were enrolled. The PP group included 1132 (22.6%) patients, and the SP group included 3875 (77.4%) patients. Of the 1132 patients, inappropriate use of aspirin was determined in 100% of the patients according to the ESC guidelines, and 71% of the patients according to the USPTF guidelines. Multivariate logistic regression analysis showed age OR: 0.98 CI (0.97-0.99) P = .037, smoking OR: 0.60 CI (0.44-0.82) P = .001, heart failure OR: 2.11 CI (1.14-3.92) P = .017, hypertension OR: 0.51 CI (0.36-0.74) P < .001, diabetes mellitus OR: 0.34 CI (0.25-0.47) P < .001, oral anticoagulant use OR: 3.01 CI (1.10-8.25) P = .032, and female sex OR: 2.73 CI (1.96-3.80) P < .001 were independent predictors of inappropriate aspirin use in PP patients. CONCLUSION: Although there are considerable differences between the USPTF and the ESC guidelines with respect to recommendations for aspirin use in PP, inappropriate use of aspirin in Turkey is frequent in real-world practice for both guidelines. Besides, heart failure, oral anticoagulant use, and the female sex of the patients were independent predictors of inappropriate use of aspirin.

Aspirin in primary prevention: the triumph of clinical judgement over complex equations.

Aspirin, in 2017, has celebrated its 120th birthday. The efficacy and safety of low-dose aspirin in secondary prevention of cardiovascular disease is well supported by many studies, instead in primary prevention it remains controversial, especially in the aftermath of the publication in 2018 of three novel primary prevention randomized clinical trials, showing that the benefit of low-dose aspirin, although additive to that of statin, is counterbalanced by an excess of (mainly gastrointestinal) bleeding events. The signal for a net benefit seems to be even more controversial in the elderly starting aspirin after the age of 70 years. While international guidelines have promptly downgraded their recommendations to more conservative indications, the practicing clinician is called to make the effort to individualize the treatment, after careful evaluation of the haemorrhagic risk vis-a-vis the risk to develop, in the mid-term and long-term follow-up, major cardiovascular events or cancer. This is a particularly complex task, given the different immediate and long-term impact of diverse outcomes on health, the dynamic nature over time of the benefit/risk balance, prompting periodic re-assessments of its indication, and the interindividual variability in aspirin response. The chemopreventive properties of aspirin, anticipated by a large body of epidemiological and mechanistic evidence, are awaiting their final confirmation by the long-term follow-up of the latest trials specifically designed to assess this endpoint, with the expectation to subvert the delicate benefit/risk balance of aspirin in primary prevention. This review is intended to provide an interpretation of past and current evidence to guide clinical decision making on the contemporary patient.

Optimising antiplatelet utilisation in the acute care setting: a novel threshold for medical intervention in suspected acute coronary syndromes.

OBJECTIVES: To construct a model to optimise and personalise recommendations for antiplatelet prescription for patients with suspected acute coronary syndrome (ACS). Acknowledging that emergency physicians work with diagnostic uncertainty, we sought to identify the point at which the probability of ACS is sufficiently high that the benefits of antiplatelet treatment outweigh the risks. Second, we evaluated the projected clinical impact of this approach by using a clinical prediction model (Troponin-only Manchester Acute Coronary Syndromes (T-MACS)) to calculate the probability of ACS. METHODS: We conducted three systematic reviews, quantifying the effects of ticagrelor, clopidogrel or aspirin-alone treatment strategies for ACS (November 2017). We extracted data for (a) clinical outcomes and (b) weighted patient preferences (utilities) for each outcome. We then constructed utilitarian models, simulating the probability of clinical outcomes with different treatment strategies. This identified the threshold probability of ACS at which each treatment strategy became superior.We validated this approach in a prospective diagnostic study including patients with suspected ACS that was conducted at two large UK teaching hospitals (St George's Hospital London recruited October 2015 to June 2017 and Manchester Royal Infirmary: February 2015 to August 2017). We calculated the probability of ACS using T-MACS. The diagnosis of ACS was adjudicated based on serial high-sensitivity troponin testing and 30-day follow-up. RESULTS: We constructed three models using data from six studies. Prescribing ticagrelor had greatest overall benefit when the probability of ACS exceeded 8.0%. Below that threshold, aspirin alone yielded greater benefit. The validation study included 660 patients, of which 87 (13.2%) had ACS. Prescription of combined antiplatelet strategy to patients with >8% probability of ACS had greater utility than aspirin alone. CONCLUSION: Treatment with ticagrelor appears to yield greater net benefit for patients when the probability of ACS >8%. The clinical and cost-effectiveness of this 'precision medicine' approach warrants further study.

ACOG Committee Opinion No. 743 Summary: Low-Dose Aspirin Use During Pregnancy.

Low-dose aspirin has been used during pregnancy, most commonly to prevent or delay the onset of preeclampsia. The American College of Obstetricians and Gynecologists issued the Hypertension in Pregnancy Task Force Report recommending daily low-dose aspirin beginning in the late first trimester for women with a history of early-onset preeclampsia and preterm delivery at less than 34 0/7 weeks of gestation, or for women with more than one prior pregnancy complicated by preeclampsia. The U.S. Preventive Services Task Force published a similar guideline, although the list of indications for low-dose aspirin use was more expansive. Daily low-dose aspirin use in pregnancy is considered safe and is associated with a low likelihood of serious maternal, or fetal complications, or both, related to use. The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine support the U.S. Preventive Services Task Force guideline criteria for prevention of preeclampsia. Low-dose aspirin (81 mg/day) prophylaxis is recommended in women at high risk of preeclampsia and should be initiated between 12 weeks and 28 weeks of gestation (optimally before 16 weeks) and continued daily until delivery. Low-dose aspirin prophylaxis should be considered for women with more than one of several moderate risk factors for preeclampsia. Women at risk of preeclampsia are defined based on the presence of one or more high-risk factors (history of preeclampsia, multifetal gestation, renal disease, autoimmune disease, type 1 or type 2 diabetes, and chronic hypertension) or more than one of several moderate-risk factors (first pregnancy, maternal age of 35 years or older, a body mass index greater than 30, family history of preeclampsia, sociodemographic characteristics, and personal history factors). In the absence of high risk factors for preeclampsia, current evidence does not support the use of prophylactic low-dose aspirin for the prevention of early pregnancy loss, fetal growth restriction, stillbirth, or preterm birth.

ACOG Committee Opinion No. 743: Low-Dose Aspirin Use During Pregnancy.

Low-dose aspirin has been used during pregnancy, most commonly to prevent or delay the onset of preeclampsia. The American College of Obstetricians and Gynecologists issued the Hypertension in Pregnancy Task Force Report recommending daily low-dose aspirin beginning in the late first trimester for women with a history of early-onset preeclampsia and preterm delivery at less than 34 0/7 weeks of gestation, or for women with more than one prior pregnancy complicated by preeclampsia. The U.S. Preventive Services Task Force published a similar guideline, although the list of indications for low-dose aspirin use was more expansive. Daily low-dose aspirin use in pregnancy is considered safe and is associated with a low likelihood of serious maternal, or fetal complications, or both, related to use. The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine support the U.S. Preventive Services Task Force guideline criteria for prevention of preeclampsia. Low-dose aspirin (81 mg/day) prophylaxis is recommended in women at high risk of preeclampsia and should be initiated between 12 weeks and 28 weeks of gestation (optimally before 16 weeks) and continued daily until delivery. Low-dose aspirin prophylaxis should be considered for women with more than one of several moderate risk factors for preeclampsia. Women at risk of preeclampsia are defined based on the presence of one or more high-risk factors (history of preeclampsia, multifetal gestation, renal disease, autoimmune disease, type 1 or type 2 diabetes, and chronic hypertension) or more than one of several moderate-risk factors (first pregnancy, maternal age of 35 years or older, a body mass index greater than 30, family history of preeclampsia, sociodemographic characteristics, and personal history factors). In the absence of high risk factors for preeclampsia, current evidence does not support the use of prophylactic low-dose aspirin for the prevention of early pregnancy loss, fetal growth restriction, stillbirth, or preterm birth.

European guidelines on perioperative venous thromboembolism prophylaxis: Aspirin.

: There is a good rationale for the use of aspirin in venous thromboembolism prophylaxis in some orthopaedic procedures, as already proposed by the 9th American College of Chest Physicians' guidelines (Grade 1C). We recommend using aspirin, considering that it may be less effective than or as effective as low molecular weight heparin for prevention of deep vein thrombosis and pulmonary embolism after total hip arthroplasty, total knee arthroplasty and hip fracture surgery (Grade 1C). Aspirin may be less effective than or as effective as low molecular weight heparins for prevention of deep vein thrombosis and pulmonary embolism after other orthopaedic procedures (Grade 2C). Aspirin may be associated with a low rate of bleeding after total hip arthroplasty, total knee arthroplasty and hip fracture surgery (Grade 1B). Aspirin may be associated with less bleeding after total hip arthroplasty, total knee arthroplasty and hip fracture surgery than other pharmacological agents (Grade 1B). No data are available for other orthopaedic procedures. We do not recommend aspirin as thromboprophylaxis in general surgery (Grade 1C). However, this type of prophylaxis could be interesting especially in low-income countries (Grade 2C) and adequate large-scale trials with proper study designs should be carried out (Grade 1C).

Effect of Antithrombotic Therapy and Long Endoscopic Submucosal Dissection Procedure Time on Early and Delayed Postoperative Bleeding.

BACKGROUND: Recent updated guidelines of the Japanese Society of Gastroenterology recommend the use of a single dose of antiplatelet agents in patients undergoing endoscopic submucosal dissection (ESD). However, the postoperative bleeding risk after gastric ESD associated with the continuation or interruption of antithrombotic therapy remains controversial. We aimed to evaluate whether certain factors including interrupted antithrombotic therapy could affect early and delayed post-ESD bleeding risk. METHODS: Three hundred sixty-four patients with gastric neoplasms were treated with ESD at our hospital between October 2005 and December 2012. Seventy-four patients with interrupted antithrombotic therapy were undertaken with ESD. Early and delayed postoperative bleeding patterns were estimated. Various clinical characteristics such as gender, age, tumor location, tumor size, ESD procedure time, platelet count, and comorbidity were evaluated. RESULTS: There was a significant difference (p = 0.042) in the ESD procedure time between the patients with postoperative bleeding and those without it. There was no significant difference in postoperative bleeding between the patients on antithrombotic therapy and not on it. Moreover, interrupted antithrombotic therapy and platelet count were significantly (p = 0.0461 and p = 0.0059, respectively) associated with early postoperative bleeding in multivariate analysis. In addition, in univariate analysis, ESD procedure time was significantly (p = 0.041) associated with delayed postoperative bleeding. CONCLUSIONS: Antithrombotic therapy and prolonged ESD procedure time were significantly associated with early and delayed postoperative bleeding, respectively.

Expert position paper on prolonged dual antiplatelet therapy in secondary prevention following myocardial infarction.

The protective effect of dual antiplatelet therapy (DAPT) following acute coronary syndrome is undisputed, but its duration is subject of debate. Several studies show that prolonged therapy provides a clinical benefit in patients following acute coronary syndrome. The aim of this position paper authored by Austrian experts is to outline the current evidence and provide an overview of recent studies. It is also intended to serve as a practical guide to identify those patients who may benefit from prolonged DAPT.

Reporting on the Strategies Needed to Implement Proven Interventions: An Example From a "Real-World" Cross-Setting Implementation Study.

UNLABELLED: The objective of this study was to empirically demonstrate the use of a new framework for describing the strategies used to implement quality improvement interventions and provide an example that others may follow. Implementation strategies are the specific approaches, methods, structures, and resources used to introduce and encourage uptake of a given intervention's components. Such strategies have not been regularly reported in descriptions of interventions' effectiveness, or in assessments of how proven interventions are implemented in new settings. This lack of reporting may hinder efforts to successfully translate effective interventions into "real-world" practice. A recently published framework was designed to standardize reporting on implementation strategies in the implementation science literature. We applied this framework to describe the strategies used to implement a single intervention in its original commercial care setting, and when implemented in community health centers from September 2010 through May 2015. Per this framework, the target (clinic staff) and outcome (prescribing rates) remained the same across settings; the actor, action, temporality, and dose were adapted to fit local context. The framework proved helpful in articulating which of the implementation strategies were kept constant and which were tailored to fit diverse settings, and simplified our reporting of their effects. Researchers should consider consistently reporting this information, which could be crucial to the success or failure of implementing proven interventions effectively across diverse care settings. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02299791.

Near-infrared chemical imaging (NIR-CI) as a process monitoring solution for a production line of roll compaction and tableting.

In the present study the application of near-infrared chemical imaging (NIR-CI) supported by chemometric modeling as non-destructive tool for monitoring and assessing the roller compaction and tableting processes was investigated. Based on preliminary risk-assessment, discussion with experts and current work from the literature the critical process parameter (roll pressure and roll speed) and critical quality attributes (ribbon porosity, granule size, amount of fines, tablet tensile strength) were identified and a design space was established. Five experimental runs with different process settings were carried out which revealed intermediates (ribbons, granules) and final products (tablets) with different properties. Principal component analysis (PCA) based model of NIR images was applied to map the ribbon porosity distribution. The ribbon porosity distribution gained from the PCA based NIR-CI was used to develop predictive models for granule size fractions. Predictive methods with acceptable R(2) values could be used to predict the granule particle size. Partial least squares regression (PLS-R) based model of the NIR-CI was used to map and predict the chemical distribution and content of active compound for both roller compacted ribbons and corresponding tablets. In order to select the optimal process, setting the standard deviation of tablet tensile strength and tablet weight for each tablet batch was considered. Strong linear correlation between tablet tensile strength and amount of fines and granule size was established, respectively. These approaches are considered to have a potentially large impact on quality monitoring and control of continuously operating manufacturing lines, such as roller compaction and tableting processes.

Lysine acetylsalicylate ameliorates lung injury in rats acutely exposed to paraquat.

BACKGROUND: Paraquat (PQ), an effective and widely used herbicide, has been proven to be safe when appropriately applied to eliminate weeds. However, PQ poisoning is an extremely frustrating clinical condition with a high mortality and with a lack of effective treatments in humans. PQ mainly accumulates in the lung, and the main molecular mechanism of PQ toxicity is based on redox cycling and intracellular oxidative stress generation. The aim of this study was to evaluate whether lysine acetylsalicylate (LAS) could protect the lung from the damage of PQ poisoning and to study the mechanisms of protection. METHODS: A model of PQ poisoning was established in 75 Sprague-Dawley rats by intragastric administration of 50 mg/kg PQ, followed by treatment with 200 mg/kg of LAS. The rats were randomly divided into sham, PQ, and PQ + LAS groups, with 25 in each group. We assessed and compared the malonaldehyde (MDA) content, superoxide dismutase activity (SOD), glutathion peroxidase (GSH-Px), and catalase (CAT) in serum and lung and the hydroxyproline (HYP) content, pathological changes, apoptosis and expression of Bcl-2/Bax protein in lung of rats on days 1, 3, 7, 14 and 21 after PQ poisoning and LAS treatment. RESULTS: Compared to the PQ group rats, early treatment with LAS reduced the MDA and HYP contents, and increased the SOD, GSH-Px, and CAT activities in the serum and lung on days 1, 3, 7, 14, and 21 after PQ poisoning (all P < 0.05). After early LAS treatment, the apoptotic rate and Bax expression of lung decreased, the Bcl-2 expression increased, and the Bcl-2/Bax ratio increased, compared to the PQ group rats. Furthermore, the pathological results of lungs revealed that after LAS treatment, early manifestations of PQ poisoning, such as hemorrhage, edema and inflammatory-cell infiltration, were improved to some degree, and collagen fibers in the pulmonary interstitium were also obviously reduced. CONCLUSION: In this rat model of PQ poisoning, LAS effectively ameliorated the lung injury induced by PQ, possibly through antioxidation, anti-fibrosis, anti-apoptosis, and anticoagulation.

Content uniformity studies in tablets by NIR-CI.

Near infrared chemical imaging (NIR-CI) is attracting growing interest in pharmaceutical analysis by virtue of its ability to provide a wealth of information from a single sample. Among others, NIR-CI has enabled the determination of the quantitative composition and distribution of acetylsalicylic (ASA) from the analysis of commercial tablets. In this work, we analyzed ASA commercial tablets of four different brands purchased at local chemists. The nominal ASA concentration for the brands was calculated from the nominal content and averaged weight of tablets. The tablets were found to span an ASA concentration range of 71-82%, and to differ in size and composition between brands. The API content and its homogeneity distribution were determined by applying quantitative algorithm to global hyperspectral image of ten tablets. Multivariate curve resolution-alternating least squares (MCR-ALS) is used to quantify each pixel in the images to obtain appropriate concentration maps. No prior calibration or reference data were needed for quantitation and results are close to the nominal content used as reference. Application to an image for 10 tablets and an individual tablet quantitation of the API allowed us to obtain the Accepted Value (AV) as defined by the European Pharmacopoeia. We conclude that all brands meet the pharmacopoeia specifications.

An integrated Quality by Design (QbD) approach towards design space definition of a blending unit operation by Discrete Element Method (DEM) simulation.

A combined Quality by Design (QbD) and Discrete Element Model (DEM) simulation-approach is presented to characterize a blending unit operation by evaluating the impact of formulation parameters and process variables on the blending quality and blending end point. Understanding the variability of both the API and the excipients, as well as their impact on the blending process are critical elements for blending QbD. In a first step, the QbD-methodology is systematically used to (1) establish the critical quality attribute content uniformity and to link this CQA to its surrogate blend homogeneity, (2) identify potentially critical input factors that may affect blending operation quality and (3) risk-rank these factors to define activities for process characterization. Subsequently, a DEM-simulation-based characterization of the blending process is performed. A statistical evaluation is finally presented, relating blend homogeneity of systems with low particle number to the regulatory requirements. Data are then used to map out a three-dimensional knowledge space, providing parameters to define a design space and set up an appropriate control strategy.

Isotopic 13C NMR spectrometry to assess counterfeiting of active pharmaceutical ingredients: site-specific 13C content of aspirin and paracetamol.

Isotope profiling is a well-established technique to obtain information about the chemical history of a given compound. However, the current methodology using IRMS can only determine the global (13)C content, leading to the loss of much valuable data. The development of quantitative isotopic (13)C NMR spectrometry at natural abundance enables the measurement of the (13)C content of each carbon within a molecule, thus giving simultaneous access to a number of isotopic parameters. When it is applied to active pharmaceutical ingredients, each manufactured batch can be characterized better than by IRMS. Here, quantitative isotopic (13)C NMR is shown to be a very promising and effective tool for assessing the counterfeiting of medicines, as exemplified by an analysis of aspirin (acetylsalicylic acid) and paracetamol (acetaminophen) samples collected from pharmacies in different countries. It is proposed as an essential complement to (2)H NMR and IRMS.