Research LettersEffect of ibuprofen on cardioprotective effect of aspirin
Summary
Treatment with ibuprofen might limit the cardioprotective effects of aspirin. We aimed to assess whether patients with known cardiovascular disease who take low-dose aspirin and ibuprofen have increased risk of cardiovascular mortality. We studied 7107 patients who were discharged after first admission for cardiovascular disease between April, 1989, and April, 1997, and who were prescribed low-dose aspirin (<325 mg/day) and survived for at least 1 month. Compared with those who used aspirin alone, patients taking aspirin plus ibuprofen had an increased risk of all-cause mortality (adjusted hazard ratio 1·93, 95% CI 1·30–2·87, p=0·0011) and cardiovascular mortality (1·73, 1·05–2·84, p=0·0305). Our finding lends support to the hypothesis that ibuprofen may interact with the cardioprotective effects of aspirin, at least in patients with established cardiovascular disease.
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Cited by (430)
Effects of acetylsalicylic acid alone or with omega-3 in patients with chronic coronary artery disease
2023, REC: CardioClinicsAntiplatelet agents such as acetylsalicylic acid (ASA) play a prominent role in preventing atherothrombosis. However, low-responsive patients who will not benefit from an increased dosage of this drug, which can cause bleeding and gastrointestinal irritation, need to be identified. Drugs such as omega-3 fatty acids, which enhance the vasodilating condition and diminish platelet aggregation, can potentiate the anti-aggregating effects of ASA, avoiding its side effects. Thus, we assessed the alternative use of 200 mg/day of ASA and 100 mg/day of this drug combined with 1 g of omega-3 in 152 patients with chronic coronary artery disease.
Our analysis included platelet function (ASPItest), TBX2 concentrations (ELISA), and SNPs polymorphisms in the rs3842787 and rs3842798 regions of the PTGS1 gene of the COX-1 enzyme and the rs5918 region of the ITGB3 gene of the fibrinogen's receptor subunit glycoprotein IIIa.
ASPItest detected 38 non-responders. The reduction of ASPItest values was more significant in this group than in responders and fell to levels of responders in non-responders of the 200 mg/day treatment. A rare allele of rs3842787 is associated with a worse ASPItest response, and the rare allele of the rs5918 polymorphism with a worse response related to TBX2 concentration. Both treatments showed no statistically significant difference in hematuria or bleeding, constituting safe treatment alternatives, and omega-3 treatment reduced monocyte levels.
Our results underscore the usefulness of pharmacogenetics for personalized treatments, avoiding gastrointestinal effects and undesirable bleeding.
El ácido acetilsalicílico (AAS) es ampliamente utilizado para prevenir la trombosis arterial. Sin embargo, deben identificarse pacientes refractarios para los cuales dosis altas de AAS son ineficaces y pueden causar irritación gastrointestinal y hemorragia. El fármaco omega-3 puede aumentar los efectos anticoagulantes del AAS y evitar sus efectos colaterales. Por ese motivo evaluamos el uso de 200 mg/día de AAS o 100 mg/día de AAS combinado con 1 g de omega-3 en 152 pacientes con enfermedad coronaria crónica.
Se analizaron la función plaquetaria (ASPItest), las concentraciones de TBX2 (ELISA) y polimorfismos de SNP en las regiones rs3842787 y rs3842798 del gen PTGS1 de la enzima COX1y la región rs5918 del gen ITGB3 de la subunidad glicoproteína IIIa del receptor de fibrinógeno.
El ASPItest detectó 38 pacientes refractarios. La reducción de la función plaquetaria fue más significativa en este grupo que en los respondedores, cayendo a niveles de respondedores en los refractarios al tratamiento con 200 mg/día. Un alelo raro de rs3842787 está asociado a una peor respuesta al ASPItest, y un alelo raro del polimorfismo rs5918, a una peor respuesta en el análisis de la concentración de TBX2. Los tratamientos analizados no mostraron evidencia estadísticamente significativa de hematuria o de sangrado, y el tratamiento con omega-3 mostró reducción en los niveles de monocitos.
La farmacogenética es una herramienta indispensable para una medicina personalizada con tratamientos que eviten efectos gastrointestinales y hemorragias, como los descritos en este estudio.
β-Cyclodextrin functionalized magnetic nanoparticles for the removal of pharmaceutical residues in drinking water
2022, Journal of Industrial and Engineering ChemistryTrace amounts of pharmaceuticals and personal care products (PPCPs) are found in our water systems, and they are known to have adverse effects on wildlife and human at the ng/L to μg/L range, below the detection limit of most water analytical instruments. Methacrylate acid (MAA)-ethyl acrylate (EA) colloidal scaffolds were prepared via emulsion polymerization and used as templates for the in-situ co-precipitation of Fe2+ to produce stable functional magnetic nanoparticles (MNPs) (<500 nm) decorated with β-cyclodextrin (β-CD) (FMNP). Emulsion polymerization with the controlled addition of monomer mixtures allowed for good size control, and silica coating was introduced to prevent the oxidation of FMNP. The superparamagnetic FMNP with high saturation magnetization (33 emu/g) could be readily separated from water using a high gradient magnetic separator (HGMS). Procaine hydrochloride (PrHy) was used as a model pharmaceutical residue to evaluate the performance of the FMNP, and 53.65 mg PrHy/g FMNP was absorbed using 600 ppm FMNP. A fast (30 min) adsorption kinetic follows the Pseudo-first-order kinetic model that described the physical adsorption through a 1 to 1 host–guest inclusion mechanism. And the adsorption behavior followed the Freundlich isotherm with a linear adsorption performance. The proposed system is scalable and adaptable to existing water treatment processes, and it can be used for the detection of low concentration pharmaceuticals via a pre-concentrating strategy.
Résistance à l'aspirine: l'ennemi de mon ami est mon ennemi
2021, Annales de Cardiologie et d'AngeiologieL'aspirine n'offre pas une protection infaillible contre le risque de survenue d'un évènement ischémique aigu. Il existe une variabilité interindividuelle de l'efficacité de cette molécule pour inhiber l'agrégation plaquettaire. La résistance biologique à l'aspirine correspond à l'incapacité de l'aspirine à produire une inhibition efficace de la fonction d'agrégation et/ou de la biosynthèse de thromboxane A2. Elle repose sur les résultats de tests fonctionnels d'agrégation ou de dosage des métabolites du thromboxane A2. Ces méthodes souffrent d'un manque de corrélation et de reproductibilité. La technique de référence, l'agrégométrie optique à l'acide arachidonique, nécessite une expertise technique avancée. La prévalence de la résistance dans les populations relevant d'un traitement par aspirine avoisine 25 %, mais varie grandement en fonction du test et de la population considérés. Elle constitue un marqueur de risque : tout test confondu le risque de survenue d'un événement cardiovasculaire est approximativement multiplié par 4 chez les sujets présentant une résistance à l'aspirine. Cependant, les modifications thérapeutiques guidées par la mise en évidence d'une résistance n'ont jamais prouvé leur efficacité sur des critères cliniques et le recours aux tests fonctionnels n'est pas recommandé en routine et doit être réservé à des situations cliniques particulières. Cependant des stratégies de majoration de dose ou de fréquence des prises ont montré des résultats encourageants sur des critères pharmacodynamiques. Les mécanismes sous-tendant sont nombreux, souvent débattus et mal documentés. On peut les séparer en trois groupes distincts : pharmacocinétiques, pharmacodynamiques liés de la voie du thromboxane-A2 ou indépendants de cette voie.
Low dose aspirin is an efficient antiplatelet agent to decrease the risk of occlusive arterial events, however it is not infallible. Aspirin resistance describe its inability to block the formation of thromboxane A2 in platelets and/or to produce an inhibitory effect on platelet aggregation. Detection of aspirin resistance relies on the results of various platelet function tests or on blood and urinary thromboxane metabolites concentrations, but these methods show very low correlation and reproducibility. Moreover, light-transmission aggregometry using arachidonic acid, known as the reference functional assay, requires technical expertise. The incidence rate of aspirin resistance amoung populations suffering from cardiovascular diseases is about 25%, however there is a wide variability depending on the specificity of the used test and the clinical features of the considered population.
Aspirin resistance is associated with the recurrence of arterial occlusive events: the odds ratio is about 4 all tests combined, therefore it could be considered as a risk marker. Evidence is lacking regarding the relevance of these tests to resort an intensification of the antithrombotic treatment, and experts recommend to reserve their use for high-risk situations. Nevertheless several studies have explored the effect of dose increases or intake frequency increases, and revealed encouraging results regarding pharmacodynamic endpoints. The reasons for aspirin resistance are numerous, often remain debate, and can accumulate to result in poor response to aspirin.
Role of oxylipins generated from dietary PUFAs in the modulation of endothelial cell function
2020, Prostaglandins Leukotrienes and Essential Fatty AcidsOxylipins, which are circulating bioactive lipids generated from polyunsaturated fatty acids (PUFAs) by cyclooxygenase, lipooxygenase and cytochrome P450 enzymes, have diverse effects on endothelial cells. Although studies of the effects of oxylipins on endothelial cell function are accumulating, a review that provides a comprehensive compilation of current knowledge and recent advances in the context of vascular homeostasis is lacking. This is the first compilation of the various in vitro, ex vivo and in vivo reports to examine the effects and potential mechanisms of action of oxylipins on endothelial cells. The aggregate data indicate docosahexaenoic acid-derived oxylipins consistently show beneficial effects related to key endothelial cell functions, whereas oxylipins derived from other PUFAs exhibit both positive and negative effects. Furthermore, information is lacking for certain oxylipin classes, such as those derived from α-linolenic acid, which suggests additional studies are required to achieve a full understanding of how oxylipins affect endothelial cells.
Comparison of Oral Ibuprofen at Three Single-Dose Regimens for Treating Acute Pain in the Emergency Department: A Randomized Controlled Trial
2019, Annals of Emergency MedicineCitation Excerpt :It has multiple drug-drug interactions, many of which arise from the reduction in glomerular filtration induced by blockade of cyclooxygenase or by competitive displacement of the second drug from protein-binding sites.3 Coadministration of ibuprofen with aspirin results in antagonism of the irreversible platelet inhibition induced by aspirin and loss of cardioprotective function; combination of ibuprofen with warfarin leads to worsening of gastrointestinal hemorrhage; with steroids, it leads to peptic ulcer disease; with diuretics and angiotensin-converting enzyme inhibitors, it elevates systolic blood pressure and worsens renal functions; and it increases toxicity of lithium.3-5 Editor’s Capsule Summary
Nonsteroidal anti-inflammatory drugs (NSAIDs) are used extensively for the management of acute pain, with ibuprofen being one of the most frequently used oral analgesics in the emergency department (ED). We compare the analgesic efficacy of oral ibuprofen at 3 different doses for adult ED patients with acute pain.
This was a randomized, double-blind trial comparing analgesic efficacy of 3 doses of oral ibuprofen (400, 600, and 800 mg) in adult ED patients with acute painful conditions. Primary outcome included difference in pain scores between the 3 groups at 60 minutes.
We enrolled 225 subjects (75 per group). The difference in mean pain scores at 60 minutes between the 400- and 600-mg groups was –0.14 (95% confidence interval [CI] –0.67 to 0.39); between the 400- and 800-mg groups, 0.14 (95% CI –0.65 to 0.37); and between the 600- and 800-mg groups, 0.00 (95% CI –0.47 to 0.47). Reductions in pain scores from baseline to 60 minutes were similar for all subjects in each of the 3 groups. No adverse events occurred in any group.
Oral ibuprofen administered at doses of 400, 600, and 800 mg has similar analgesic efficacy for short-term pain relief in adult patients presenting to the ED with acute pain.
Non-steroidal anti-inflammatory drugs (NSAIDs) are reversible inhibitors of cyclo-oxygenase (COX), mainly used for the symptomatic relief of pain, whether traumatic, infectious, episodic or rheumatologic. Use for the long-term relief of inflammation is waning with the emergence of specific biotherapies. Their effects are related to potency, dosage, and pharmacokinetic or galenic considerations. Adverse reactions are mostly related to COX inhibition, and to the relative COX1 and COX2 inhibition. Over the years have resulted in the withdrawal of some NSAIDs. The most common adverse reactions are: gastrointestinal (COX1) which have declined over time with the emergence of more COX1 sparing drugs and gastroprotection; renal, with an impact on renal function and sodium extraction that is associated with hypertension, heart failure exacerbation, and stress-related renal failure; allergic skin reactions; increased transaminases and acute liver injury which may be idiosyncratic or immunoallergic; increased risk of acute coronary syndromes, initially associated with high-dose long-term use of COX2 specific inhibitors in controlled clinical trials, though more recently there have been indications from poorly controlled observational studies that they could occur with most NSAIDs. Event rates in patients with no overt coronary heart disease are vanishingly low, and the real magnitude of the issue in the treatment of common pain is still unknown. Considering their purely symptomatic effects, they should be used at the lowest possible dose for the shortest possible time, based on the symptomatic relief of pain or fever.