Safety Of Non-steroidal Anti-inflammatory Drugs Research Articles

Insights from pharmacovigilance and pharmacodynamics on cardiovascular safety signals of NSAIDs.

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat fever, pain, and inflammation. Concerns regarding their cardiovascular safety have been raised. However, the underlying mechanism behind these events remains unknown. We aim to investigate the cardiovascular safety signals and receptor mechanisms of NSAIDs, employing a comprehensive approach that integrates pharmacovigilance and pharmacodynamics. This study utilized a pharmacovigilance-pharmacodynamic approach to evaluate the cardiovascular safety of NSAIDs and explore potential receptor mechanisms involved. Data were analyzed using the OpenVigil 2.1 web application, which grants access to the FDA Adverse Event Reporting System (FAERS) database, in conjunction with the BindingDB database, which provides target information on the pharmacodynamic properties of NSAIDs. Disproportionality analysis employing the Empirical Bayes Geometric Mean (EBGM) and Reporting Odds Ratio (ROR) methods was conducted to identify signals for reporting cardiovascular-related adverse drug events (ADEs) associated with 13 NSAIDs. This analysis encompassed three System Organ Classes (SOCs) associated with the cardiovascular system: blood and lymphatic system disorders, cardiac disorders, and vascular disorders. The primary targets were identified through the receptor-NSAID interaction network. Ordinary least squares (OLS) regression models explored the relationship between pharmacovigilance signals and receptor occupancy rate. A total of 201,231 reports of cardiovascular-related ADEs were identified among the 13 NSAIDs. Dizziness, anemia, and hypertension were the most frequently reported Preferred Terms (PTs). Overall, nimesulide and parecoxib exhibited the strongest signal strengths of ADEs at SOC levels related to the cardiovascular system. On the other hand, our data presented naproxen and diclofenac as drugs of comparatively low signal strength. Cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) were identified as central targets. OLS regression analysis revealed that the normalized occupancy rate for either COX-1 or COX-2 was significantly inversely correlated with the log-transformed signal measures for blood and lymphatic system disorders and vascular disorders, and positively correlated with cardiac disorders and vascular disorders, respectively. This suggests that higher COX-2 receptor occupancy is associated with an increased cardiovascular risk from NSAIDs. Cardiovascular safety of NSAIDs may depend on pharmacodynamic properties, specifically, the percentage of the occupied cyclooxygenase isoenzymes. More studies are needed to explore these relations and improve the prescription process.

A novel deep learning approach for optimizing preparation and usage of nonsteroidal anti-inflammatory drugs (NSAIDs) in spine care

Nonsteroidal anti-inflammatory drugs (NSAIDs) are essential for the management of pain and inflammation brought by illnesses of the spine. NSAIDs are essential in the treatment of inflammation and pain in a variety of spinal disorders. In order to relieve pain for patients and enhance their quality of life, NSAIDs should be used effectively. The effectiveness and safety of NSAIDs for spinal pain were assessed using a systematic review and meta-analysis. We gathered the patient data. The insufficient data is cleaned using tokenization and the data extraction employs Term Frequency-Inverse Document Frequency (TF-IDF). A Monarch Butterfly Optimization Dynamic Generative Adversarial Networks (MBO+DGAN) for the preparation and use of NSAIDs in spine care. Our studies show the possibility of the MBO+DGAN strategy to enhance the administration of NSAIDs in spine care, leading to improved clinical results, patient experiences and possibly lower healthcare costs. The MBO+DGAN assesses a method's effectiveness by evaluating its performance in terms of Accuracy (95%), Sensitivity (96%), Precision (97%) and Specificity (94%). The opportunity to use MBO+DGAN to improve how NSAIDs are created and utilized in the complex world of spine care. This technique offers an effective approach to enhance patient care and outcomes in the difficult field of spine healthcare by enabling customized treatment plans.

Modern view on the effectiveness and safety of non-steroidal anti-inflammatory drugs

Issues of the effectiveness and safety of drugs remain relevant and controversial. The benefits and risks of drug therapy are two facets of one whole, called pharmacotherapy, which can have undesirable side and even negatively outweigh the benefits. The effectiveness and safety of drugs must be studied comprehensively because new effects of drugs may be discovered and new mechanisms for unregistered indications may be revealed. Moreover, a deep understanding of adverse drug reactions will allow for the accurate prescription of drugs and proper medical supervision of therapy. Nonsteroidal anti-inflammatory drugs are over-the-counter drugs perceived by patients as safe and do not require a doctor’s prescription, which can cause dangerous drug reactions, particularly when used uncontrollably. The review presents literature data from studies on the effectiveness of nonsteroidal anti-inflammatory drugs and current data on new therapeutic effects of individual drugs, risks of adverse reactions, their mechanisms, and treatment methods.

Risk of acute kidney injury after lower urinary tract reconstruction with early NSAID therapy: A propensity matched retrospective analysis

The opioid epidemic response led to increased use of postoperative, non-opioid analgesia. Some pediatric urologists do not routinely use non-steroidal anti-inflammatory drugs (NSAIDs) for fear of causing acute kidney injury (AKI). While previous studies have demonstrated the safety and efficacy of NSAIDs in children, safety after lower urinary tract reconstruction has not been well characterized. ptUsing the Kidney Disease: Improving Global Outcomes (KDIGO) criteria for AKI (increase in creatinine ≥0.3mg/dL or increase in creatinine ≥1.5x baseline or urine output <0.5mL/kg/hr for 6h), we hypothesized there would be a difference in the incidence of postoperative AKI between patients who did and did not receive NSAIDs following surgery. Patients 2-18 years old who underwent lower urinary tract reconstruction (i.e., bladder augmentation and/or creation of a catheterizable channel) from 2009 to 2021 and had documented urine output were retrospectively reviewed. Chronic kidney disease (CKD) stage was calculated from creatinine and cystatin C within 6 months of surgery using the CKiD U25 equations. Patients who received NSAIDs were propensity matched on 11 characteristics with patients undergoing similar surgeries who did not receive NSAIDs. The primary outcome was incidence of AKI within 48h of surgery. The unmatched cohorts included 243 patients. Propensity matching identified 166 patients in the NSAID arm and 41 in the no NSAID arm. 26 patients with CKD stage 2-3 were included. There was no significant difference in the incidence of postoperative AKI based on any KDIGO criteria (17.1% no NSAID versus 16.3% NSAID, p=0.87). Median postoperative opioids fell from 0.88mg/kg in the no NSAID arm to 0.37mg/kg morphine equivalents in the NSAID arm, although this was not statistically significant. Log-rank testing by Kaplan-Meier analysis demonstrated no difference in time to incidence of low urine output between the groups (p=0.32). In the whole population not stratified by NSAID use, no differences were seen in AKI between those with and without CKD (16.7% with versus 17.9% without CKD). There was no difference in the incidence of postoperative AKI among patients who did and did not receive NSAIDs after lower urinary tract reconstruction, excluding those with advanced CKD. These results support that postoperative NSAIDs were an unlikely source of AKI. However, AKI remained a risk following these surgeries, regardless of NSAID use, likely owing to underlying disease, longer operations, and fluid shifts.

Efficacy and safety of topical NSAIDs combined with physiotherapy for frozen shoulder: a randomized controlled trial.

Frozen shoulder is a prevalent condition among individuals in their middle and later years. Invasive therapy has shown promising results in the treatment of frozen shoulders, but its widespread adoption has been hampered by high costs and the need for advanced medical technology. As a result, patients with frozen shoulders often turn to non-steroidal anti-inflammatory drugs (NSAIDs) for symptomatic relief. However, the oral administration of NSAIDs can lead to troublesome adverse effects on the gastrointestinal, cardiovascular, and urinary systems. In contrast, topical NSAIDs have gained attention for their excellent efficacy and lower adverse effects in various chronic pain conditions. Therefore, our study aimed to investigate the efficacy and safety of topical NSAIDs in improving pain and mobility among patients with frozen shoulders. A total of 108 patients experiencing moderate to severe pain and mobility impairment due to frozen shoulder were enrolled in this study. The participants were randomly assigned to either the experimental group (n=72) or the control group (n=36). The experimental group received daily treatment with the loxoprofen hydrogel patch (LOX-P) in addition to basic rehabilitation physiotherapy. The control group was treated with flurbiprofen cataplasm (FLU-C) twice a day, along with rehabilitation physiotherapy. The primary endpoint for evaluating the efficacy of the two patches was the Constant-Murley score (CMS). Clinical symptom data, adverse events, and patient satisfaction were also recorded. After 14 days of treatment, the effective rate was 66.67% (n=48) in the experimental group and 41.67% (n=15) in the control group. The overall difference in the effective rates was 25.00% (95% CI=5.20-42.52; p=0.013). The safety profiles of the two topical agents were similar, with only a few adverse events reported. The loxoprofen hydrogel patch demonstrates a significant ability to alleviate shoulder pain and restore shoulder function in the treatment of frozen shoulder, with minimal adverse reactions. Chictr.org.cn ID: ChiCTR2100052375.

Alternative Drug Safety in Children with Nonsteroidal Anti-Inflammatory Drug Hypersensitivity

Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used in the pediatric age group as pain relievers, antipyretics and anti-inflammatory drugs. Since NSAIDs are used in many medical conditions, there is a need for alternative NSAIDs to be used safely in people with hypersensitivity reactions. Selective and partially selective COX-2 inhibitors and weak COX-1 inhibitors are generally used as safe alternative drugs. The aim of this study was to evaluate safe NSAIDs determined by oral provocation tests (OPTs) according to phenotypes in children with NSAID hypersensitivity reactions. Methods: The results of the oral provocation test performed with alternative NSAIDs (paracetamol, meloxicam, nimesulide, celecoxib) in patients followed up with the diagnosis of NSAID hypersensitivity reaction in the Pediatric Immunology and Allergy Department between January 2015 and February 2023 were evaluated retrospectively. Results: During the study period, 91 patients underwent OPTs with 109 alternative drugs 48 (52.7%) of whom were girls, with a median age of 15 years. 91 patients had a history of reactions to 117 drugs. As an alternative NSAID; OPT was performed with paracetamol in 58 patients, meloxicam in 44 patients, nimesulide in 5 patients, and celecoxib in 2 patients. Since 15 patients used paracetamol safely at home, no tests were performed with paracetamol. Reactions were observed in 3 of the 73 patients (4.1%) who underwent OPT with paracetamol and in 2 of the 44 (4.5%) who underwent OPT with meloxicam. Reactions to nimesulide were also observed in the latter 2 patients (2/5, 40%), but they appeared to tolerate celecoxib. No reaction was observed in the 2 patients who were tested with celecoxib. Conclusion: Paracetamol, meloxicam, and nimesulide can be used as safe alternative drugs in most children with NSAID hypersensitivity. Selective COX-2 inhibitors should be tried as an alternative in patients who cannot tolerate them.

Effectiveness of the Use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) for Postoperative Pain Management in Patients Undergoing Major Surgical Operations at Manokwari Hospital

Postoperative pain is a common complication in patients undergoing major surgical operations, interfering with comfort and recovery and increasing the risk of further complications. This study aimed to evaluate the effectiveness of NSAIDs in managing postoperative pain at Manokwari Regional Hospital. Utilizing qualitative research methods, data was collected through observation and literature study and analyzed via data reduction, data presentation, and conclusion drawing. The findings indicate that NSAIDs effectively alleviate postoperative pain by inhibiting cyclooxygenase (COX) enzymes responsible for prostaglandin production. However, their use is limited by potential systemic side effects, including gastrointestinal disorders, kidney impairment, increased blood pressure, heart attack, and heart failure. Consequently, topical NSAID formulations are recommended to mitigate these risks. The study suggests that while NSAIDs are effective, clinicians should consider their side effects and prefer topical alternatives. Future research should explore the efficacy and safety of topical NSAIDs and alternative pain management strategies to enhance clinical practice.

The Multifaceted Effects of Non-Steroidal and Non-Opioid Anti-Inflammatory and Analgesic Drugs on Platelets: Current Knowledge, Limitations, and Future Perspectives.

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely utilized pharmaceuticals worldwide. Besides their recognized anti-inflammatory effects, these drugs exhibit various other pleiotropic effects in several cells, including platelets. Within this article, the multifaceted properties of NSAIDs on platelet functions, activation and viability, as well as their interaction(s) with established antiplatelet medications, by hindering several platelet agonists' pathways and receptors, are thoroughly reviewed. The efficacy and safety of NSAIDs as adjunctive therapies for conditions involving inflammation and platelet activation are also discussed. Emphasis is given to the antiplatelet potential of commonly administered NSAIDs medications, such as ibuprofen, diclofenac, naproxen and ketoprofen, alongside non-opioid analgesic and antipyretic medications like paracetamol. This article delves into their mechanisms of action against different pathways of platelet activation, aggregation and overall platelet functions, highlighting additional health-promoting properties of these anti-inflammatory and analgesic agents, without neglecting the induced by these drugs' side-effects on platelets' functionality and thrombocytopenia. Environmental issues emerging from the ever-increased subscription of these drugs are also discussed, along with the need for novel water treatment methodologies for their appropriate elimination from water and wastewater samples. Despite being efficiently eliminated during wastewater treatment processes on occasion, NSAIDs remain prevalent and are found at significant concentrations in water bodies that receive effluents from wastewater treatment plants (WWTPs), since there is no one-size-fits-all solution for removing all contaminants from wastewater, depending on the specific characteristics of the wastewater. Several novel methods have been studied, with adsorption being proposed as a cost-effective and environmentally friendly method for wastewater purification from such drugs. This article also presents limitations and future prospects regarding the observed antiplatelet effects of NSAIDs, as well as the potential of novel derivatives of these compounds, with benefits in other important platelet functions.

Efficacy and Safety of Pharmacist-Managed NSAIDs Deprescribing: A Jordanian Outpatient Study

Background. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to manage pain, including chronic pain conditions. However, their prolonged use is associated with significant risks, particularly gastrointestinal (GI) adverse events. This study aimed to evaluate the effectiveness and safety of a pharmacist-managed deprescribing program for NSAIDs in a Jordanian outpatient population. Methods. A convenience sample of 100 participants who had been using NSAIDs for pain management was recruited. Participants underwent a structured deprescribing intervention in collaboration with physicians. Various effectiveness and safety outcomes were assessed before and after deprescribing. Descriptive statistics and chi-square test were used for data analysis. Results. The majority of participants reported chronic pain conditions, with rheumatoid arthritis (24%) and osteoarthritis (22%) being the most prevalent. Ibuprofen (28%) and diclofenac (22%) were the most commonly used NSAIDs. The deprescribing program was associated with a significant reduction in heartburn, stomach ulcer, kidney problems and fluctuation in blood pressure readings (p&lt;0.05), and pain exacerbation. Notably, the reduction in pain exacerbation was evident (p=0.003) in the 4-month follow-up. Conclusion. A pharmacist-managed NSAIDs deprescribing program demonstrated effectiveness in reducing the risk of GI adverse events and fluctuation in blood pressure readings without causing harm during a short-term follow-up. These findings support the feasibility of implementing such programs in outpatient settings. Further long-term investigations are necessary to confirm these results.

Association of COX-inhibitors with cancer patients' survival under chemotherapy and radiotherapy regimens: a real-world data retrospective cohort analysis.

We conducted an extensive, sex-oriented real-world data analysis to explore the impact and safety of non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors (coxibs) on cancer treatment outcomes. This is particularly relevant given the role of the COX-2/PGE2 pathway in tumor cell resistance to chemotherapy and radiotherapy. The study applied a retrospective cohort design utilizing the TriNetX research database consisting of patients receiving cancer treatment in 2008-2022. The treated cohorts included patients who were prescribed with coxibs, aspirin or ibuprofen, while individuals in the control cohort did not receive these medicines during their cancer treatment. A 1:1 propensity score matching technique was used to balance the baseline characteristics in the treated and control cohorts. Then, Cox proportional hazards regression and logistic regression were applied to assess the mortality and morbidity risks among patient cohorts in a 5-year follow-up period. Use of coxibs (HR, 0.825; 95% CI 0.792-0.859 in females and HR, 0.884; 95% CI 0.848-0.921 in males) and ibuprofen (HR, 0.924; 95% CI 0.903-0.945 in females and HR, 0.940; 95% CI 0.917-0.963 in males) were associated with improved survival. Female cancer patients receiving aspirin presented increased mortality (HR, 1.078; 95% CI 1.060-1.097), while male cancer patients also had improved survival when receiving aspirin (HR, 0.966; 95% CI 0.951-0.980). Cancer subtype specific analysis suggests coxibs and ibuprofen correlated with survival, though ibuprofen and aspirin increased emergency department visits' risk. Secondary analyses, despite limited by small cohort sizes, suggest that COX inhibition post-cancer diagnosis may benefit patients with specific cancer subtypes. Selective COX-2 inhibition significantly reduced mortality and emergency department visit rates. Further clinical trials are needed to determine the optimal conditions for indication of coxibs as anti-inflammatory adjuvants in cancer treatment.

Safety of Non-steroidal Anti-inflammatory Drugs as Part of Enhanced Recovery After Laparoscopic Sleeve Gastrectomy-A Systematic Review and Meta-Analysis.

Laparoscopic sleeve gastrectomy (LSG) is an effective bariatric surgery option for managing extreme obesity in most patients. While non-steroidal anti-inflammatory drugs (NSAIDs) promise postoperative pain management after bariatric surgeries, their safety in LSG remains unexplored. In this systematic review, we studied the safety of NSAIDs following LSG reported by six studies involving 588 patients. Our study demonstrated that NSAIDs effectively alleviated the postoperative pain after LSG without major safety concerns. Most reported (>20% incidence) adverse events included postoperative nausea and vomiting (PONV, 21%). For patients undergoing LSG, NSAIDs offer a valuable option for pain management and improved care, potentially reducing opioid consumption. However, additional research is required to optimize NSAID usage and ensure safety, especially concerning renal and gastrointestinal issues.

Personalized approach to choosing an analgesic for the treatment of musculoskeletal pain

Chronic musculoskeletal pain (CMSP) associated with diseases of the musculoskeletal system is one of the global causes of suffering, disability, and a decrease in the quality of life and its duration for hundreds of millions of people on Earth. Therefore, effective pain control is among the first and most important tasks of the treatment of musculoskeletal diseases. For this purpose, a complex of medications and non-pharmacological approaches (kinesiotherapy, psychological methods, educational programs, etc.) is used. Effective, affordable and convenient nonsteroidal anti-inflammatory drugs (NSAIDs) play a fundamental role among analgesics. They belong to the “first line” drugs for the control of SMB. However, when prescribing them, it is necessary to take into account the presence of comorbid pathology as risk factors for drug complications. At the same time, naproxen is the safest NSAID in terms of cardiovascular risk. The effectiveness of this drug has been proven both in the short-term treatment of acute and long-term therapy of chronic pain. Naproxen is more effective than paracetamol and is not inferior to weak opioids and other NSAIDs, such as ibuprofen and ketorolac. The data of clinical, observational and cohort studies, as well as their meta-analysis, confirm that the risk of cardiovascular complications in the treatment with naproxen is minimal. An urgent problem in the treatment of CMSP is the combination of this pathology with sleep disorders, which determines a significant deterioration in the well-being and quality of life of patients. The use of the combined over-the-counter drug naproxen and diphenhydramine for short-term therapy of insomnia presents new possibilities of pharmacotherapy in this clinical situation.

Cardiovascular safety of non-steroidal anti-inflammatory drug use for gout: A Danish nationwide case-crossover study

Abstract Background Gout is associated with increased cardiovascular risk through inflammation and shared risk factors. Gout attacks are treated with a uric-lowering drug, such as allopurinol, and an anti-inflammatory drug, such as a non-steroidal anti-inflammatory drug (NSAID). Thus, NSAIDs could be both cardiovascular beneficial, due to their anti-inflammatory actions, and cardiovascular hazardous, due to their prothrombotic, hypertensive, and proarrhythmic actions. Yet, no study has examined the cardiovascular safety of NSAIDs for the treatment of gout. Purpose To examine the risk of major adverse cardiovascular events (MACEs) associated with NSAID use in gout patients. Methods We conducted a nationwide, population-based case-crossover study of all Danes ≥18 years of age with first-time gout during 1997–2020, who experienced a MACE (myocardial infarction, ischemic stroke, congestive heart failure, atrial fibrillation or flutter, or all-cause death) (n=103,522). The patients were identified either via a hospital diagnosis for gout (12%) or via a filling of an allopurinol prescription (88%). The exposures were use of NSAIDs overall and according to subtype (ibuprofen, naproxen, or diclofenac). An individual was considered exposed from the time of a filled prescription until the end of a use period, estimated from average use of two tablets per day. In the case-crossover design, we used four reference dates at 120, 180, 240, and 300 days before the outcome. An individual was considered exposed if the use period covered a reference date or the outcome date. We used the Mantel-Haenszel method to calculate odds ratios (ORs) with 95% confidence intervals (CIs) of the association between NSAID use and MACE. Results NSAID use was overall associated with a 15% decreased risk of MACE (OR=0.85, 95% CI: 0.83–0.87). The ORs of the association between NSAID use and the individual cardiovascular events were 0.91 (95% CI: 0.84–0.99) for myocardial infarction, 0.88 (95% CI: 0.81–0.95) for ischemic stroke, 0.89 (95% CI: 0.83–0.94) for congestive heart failure, 0.80 (95% CI: 0.75–0.85) for atrial fibrillation or flutter, and 0.77 (95% CI: 0.75–0.80) for all-cause death. The decreased risk of MACE was observed for use of ibuprofen (OR=0.91, 95% CI: 0.88–0.95) and naproxen (OR=0.78, CI: 0.70–0.86), but not for use of diclofenac (OR=1.03, 95% CI: 0.97–1.09). Conclusions In patients with first-time gout, use of ibuprofen and naproxen was associated with a slightly decreased cardiovascular risk, whereas diclofenac was not.

Nonsteroidal Anti-inflammatory Medications in Cranial Neurosurgery: Balancing Opioid-Sparing Analgesia with Bleeding Risk

Post-craniotomy pain is a common problem frequently encountered by neurosurgeons. This is typically managed with opioids; however, opioids have been shown to increase intracranial pressure by way of hypercapnia and straining from the associated constipation. Additionally, opioids can confound and mask the neurologic examination of post-craniotomy patients as well as be the nidus for a potential opioid addiction. Thus, alternative solutions for opioids have been a major topic of investigation within the neurosurgical community. Non-steroidal anti-inflammatory drugs (NSAIDs), present as a potential solution due to their non-addictive and analgesic properties, but utilization of NSAIDs in neurosurgical patients has been controversial given that NSAIDs alter platelet function. Whether the degree to which NSAIDs alter platelet function and bleeding time to clinically relevant manner has remained controversial; although, there have been several well-designed studies concluding that the utilization of NSAIDs in post-craniotomy patients does not increase the risk of postoperative bleeding. Herein, we review the pharmacology, efficacy, and safety of NSAIDs with a particular emphasis on NSAID use for post intracranial neurosurgical procedure pain management.

Management of Specific Clinical Profiles in Axial Spondyloarthritis: An Expert's Document Based on a Systematic Literature Review and Extended Delphi Process.

The management of specific clinical scenarios is not adequately addressed in national and international guidelines for axial spondyloarthritis (axSpA). Expert opinions could serve as a valuable complement to these documents. Seven expert rheumatologists identified controversial areas or gaps of current recommendations for the management of patients with axSpA. A systematic literature review (SLR) was performed to analyze the efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, conventional synthetic, biologic and targeted synthetic disease-modifying antirheumatic drugs (csDMARDs, b/tsDMARDs) in axSpA regarding controversial areas or gaps. In a nominal group meeting, the results of the SLR were discussed and a set of statements were proposed. A Delphi process inviting 150 rheumatologists was followed to define the final statements. Agreement was defined as if at least 70% of the participants voted ≥ 7 (from 1, totally disagree, to 10, totally agree). Three overarching principles and 17 recommendations were generated. All reached agreement. According to them, axSpA care should be holistic and individualized, taking into account objective findings, comorbidities, and patients' opinions and preferences. Integrating imaging and clinical assessment with biomarker analysis could also help in decision-making. Connected to treatments, in refractory enthesitis, b/tsDMARDs are recommended. If active peripheral arthritis, csDMARD might be considered before b/tsDMARDs. The presence of significant structural damage, long disease duration, or HLA-B27-negative status do not contraindicate for the use of b/tsDMARDs. These recommendations are intended to complement guidelines by helping health professionals address and manage specific groups of patients, particular clinical scenarios, and gaps in axSpA.

Principles of effective use of non-steroidal anti-inflammatory drugs

The article provides an overview of references on the rational use of nonsteroidal anti-inflammatory drugs (NSAIDs) in modern medicine. Nonsteroidal anti-inflammatory drugs are a group of drugs with different chemical structures (mostly acid derivatives) that have anti-inflammatory, analgesic, antipyretic, antiplatelet (acetylsalicylic acid, acetylsalicylate, ketoprofen, diclofenac sodium, niflumic acid, indomethacin) effects. NSAIDs are divided according to the selectivity of action relative to cyclooxygenase (COX) isoforms: non-selective COX inhibitors, selective COX-1 inhibitors, approximately equal inhibition of COX-1 and COX-2, selective COX-2 inhibitors. They are characterized by general pharmacological properties: high degree of absorption in the gastrointestinal tract; a high degree of binding to albumins; approximately the same volume of distribution; the ability to accumulate in the focus of inflammation. Indications for NSAIDs use are: acute arthritis and chronic arthritis; acute and chronic pain syndrome of various nature (lower back pain syndrome, joint and soft tissue injuries, migraine, dysmenorrhea, preoperative and postoperative pain, renal colic, fever in various rheumatic and non-rheumatic diseases). Аdditional indications for prescribing NSAIDs are: pleurisy, pericarditis, erythema nodosum, polycystic lung disease, sciatica. The most frequent and dangerous side effects include gastrointestinal, kidney complications. Special attention is paid to the cardiovascular safety of NSAIDs and, above all, COX-2 inhibitors because of risk of cardiovascular events. The most effective drug with the best tolerability should be selected for a specific patient. Before starting NSAID therapy, the patient's age, comorbidities, previous medical or surgical history, concomitant use of medications (including antiplatelet agents, anticoagulants, corticosteroids, ACE inhibitors, and selective serotonin reuptake inhibitors), H. pylori infection, and blood pressure monitoring should be considered. Keywords: inflammation, pain, side effects, gastropathy, selectivity.

COVID-19 and non-steroid anti-inflammatory drugs

The literature review deals with the analysis of the results of studies on the effectiveness and safety of nonsteroidal anti-inflammatory drugs (NSAIDs) in the intensive care programs for patients with COVID-19 in 2020–2021. NSAIDs used for other indications or low-dose aspirin do not increase the body’s sensitivity to SARS-CoV-2 and are not additional risk factors for the severity of the course and mortality from COVID-19. Therefore, in patients receiving NSAIDs or low-dose aspirin for comorbid conditions, these drugs should not be withdrawn and may be used during the treatment of COVID-19. It has now been clarified that the pro-inflammatory effect in SARS-CoV-2 is caused by prostaglandins. Suppression of their production with the help of NSAIDs can have a positive effect during the initial phase of a viral infection, before the development of acute respiratory distress syndrome. To date, the clinical benefits of low-dose aspirin for the primary prevention of thrombotic complications in hospitalized patients with COVID-19 have not been proven, and therefore it is not recommended to use aspirin for this purpose.

#5576 SYSTEMATIC REVIEW AND META-ANALYSIS OF THE SAFETY AND EFFICACY OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS FOR THE MANAGEMENT OF POSTPARTUM PAIN

Abstract Background and Aims Effective pain management is critical for postpartum recovery. While commonly prescribed, systematically-reviewed data regarding efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) are limited. Moreover, guidelines suggest avoiding NSAIDs in women with hypertensive disorders of pregnancy (HDP) due to risks of hypertension and adverse events (AE). However, these AE have not been consistently observed in cohort studies and randomised controlled trials (RCTs) following postpartum NSAID use. This systematic review aims to provide further insight into the postpartum safety and efficacy of NSAIDs. Method A systematic review of eight databases and four clinical trial registries was conducted in July 2020 (PROSPERO Protocol CRD42020196054). RCTs which assessed the safety and/or efficacy of NSAIDs in postpartum women after the year 2000 were included. The primary outcome was incidence of hypertension, with secondary outcomes categorised into three groups: hypertension, secondary safety and efficacy. Data were tabulated and analysed using R (version 4.0.2). Due to heterogeneity in study design, NSAIDs were analysed in a single group and compared with other medications (including paracetamol, opioids, and local anaesthetics) grouped based on mechanism to facilitate meta-analysis. Risk of bias was assessed using the RoB 2 tool with a plan to assess quality of evidence for the primary outcome. Results 12,172 records were identified with the inclusion of 92 RCTs. Eight studies, with four that included women with HDP, reported hypertension-related data (Table 1). The primary outcome was included in one RCT. Secondary safety outcomes such as acute kidney injury or eclampsia were not reported. The odds of nausea, vomiting and sedation were similar between groups. NSAIDs were effective when compared with placebo, as assessed by mean differences (MD) in visual assessment scores (VAS) at 12 hours (MD -1.57, 95% confidence intervals (CI) -2.47 to -0.66), 24 hours (MD -0.82, 95% CI -1.42 to -0.22) and need for additional analgesia (odds ratio 0.17, 95% CI 0.05 to 0.61). There were no significant differences in VAS between NSAIDs and other comparators at 12 and 24 hours. Further interpretation of results is limited due to heterogeneity in intervention and comparator groups, inclusion criteria and reported outcomes. Conclusion Our study confirms the efficacy of NSAIDs for postpartum pain, but current data are inconclusive regarding the risk of developing hypertension. Available data do not demonstrate trends toward AE although further research is required to determine long term, clinically-relevant outcomes to guide decision making.

Pathogenetic features of cardiovascular pathology in patients with osteoarthritis

Cardiovascular pathology occupies a leading place among all causes of death and permanent disability of the population. In recent years, there has been an increase in the number of cardiovascular comorbidity cases, which leads to a significant deterioration in the quality of life, difficulties in the selection of therapy and a worse prognosis. Cardiorheumatology is an actual and actively discussed direction in this area. One of the most common rheumatic pathologies is osteoarthritis. Researchers identify a number of factors aggravating the course of cardiovascular pathology in the presence of osteoarthritis: regular intake of non-steroidal antiinflammatory drugs, chronic pain syndrome, decreased mobility. The review provides current data on the problem under discussion, in particular, the current understanding of pathogenetic relationships. The issues of safety of non-steroidal anti-inflammatory drugs in cardiovascular patients are highlighted. The potential of using modern immunological cytokines in this group of patients are described using the example of galectin-3 as a marker of prognosis.

Topical nonsteroidal anti-inflammatory drugs for management of osteoarthritis pain: A consensus recommendation.

Osteoarthritis (OA) contributes to significant medical and socioeconomic burden in many populations. Its prevalence is expected to rise continuously owing to the combined effects of aging and increase in risk factors, including obesity, physical inactivity, and joint injuries. Pain is a hallmark presentation of OA. Topical nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended by many international guidelines as an early treatment option of the management of osteoarthritic pain. However, the use of topical NSAIDs remains low in Malaysia and appears not to be a preferred agent in managing OA pain by prescribers. There is also limited guidance from local medical bodies on the use of topical NSAIDs to manage OA pain. This consensus recommendation is intended to serve as a practical guide for healthcare practitioners on the use of topical NSAIDs in the management of OA pain. Eight statements and recommendations were finalized covering the areas of OA burden, topical NSAIDs formulations, safety and efficacy of topical NSAIDs, and patient education. Robust evidence is available to support the efficacy and safety of topical NSAIDs, with its benefits further strengthened by ease of use and access. Taking these into consideration, we recommend that healthcare practitioners advocate for the early use of topical NSAIDs over oral NSAIDs for mild-to-moderate OA pain, while engaging in a shared decision-making process with patients for optimal clinical outcomes.