Nonselective Nonselective Nonsteroidal Anti-inflammatory Drugs Research Articles

A Systematic Review and Meta-analysis of Selective Cyclooxygenase-2 Inhibitors and Non-selective Non-steroidal Anti-inflammatory Drugs for Acute Gout

Background The term “gout” refers to a broad clinical spectrum of diseases, including common and complex forms of arthritis, that affect multiple joints in a patient due to an elevated serum urate concentration. Purpose The study aims to compare the efficacy and safety of selective cyclooxygenase-2 (COX-2) inhibitors and non-selective nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of acute gout, as well as to conduct a meta-analysis on safety. Methodology As of December 2021, the literature search was conducted using authorised electronic databases such as PubMed, Embase, Web of Science, and the Cochrane Library. Results There were seven investigations included in this study’s findings. Three COX-2 inhibitors, etoricoxib, celecoxib, and meloxicam, were reportedly compared to indomethacin or diclofenac. Four hours after the initial dose, 120 mg of etoricoxib reduces pain and inflammation by diminishing erythema. At higher dosages, celecoxib is more effective than at lower doses. Meloxicam has the same efficacy as NSAIDs. The subgroup analysis revealed that the risk of adverse events was 8.0% lower in the COX-2 inhibitors group than in the non-selective NSAIDs group (risk ratio = 0.92, 95% confidence interval = 0.60 to 0.40, p-value = 0.5). Conclusion Etoricoxib, a COX-2 inhibitor, has a more potent effect and may be more effective than non-selective NSAIDs. COX-2 inhibitors are more well tolerated and reduce the risk of adverse gastrointestinal events more effectively than non-selective NSAIDs. In the treatment of gout, non-selective NSAIDs may be a suitable alternative to COX-2 inhibitors.

Агрегация тромбоцитов у женщин с нефролитиазом при назначении неселективных НПВП

Aim: to evaluate the effect of adrenergic and purinergic signaling in platelets (PLT) during COX inhibition on the severity of hematuria in women with nephrolithiasis (NLT). Material and Methods. The study was prospective and included 60 patients with imaging evidence of urinary tract stones, who were treated with high doses of non-selective non-steroidal anti-inflammatory drugs (NSAIDs) as part of lithokinetic therapy (LKT) for analgesia. The study included 30 women who had reproducible TP-receptor hyporeactivity (<45%) after 72h of LKT with non-selective NSAIDs. The severity of hematuria was assessed at the time of hospitalization and for 7 days of LCT. The activity of the TP receptor, α2-adrenergic receptor, purine P2X1- and P2Y-receptors (P2Y1, P2Y12) was studied by turbidimetric method on a ChronoLog analyzer (USA). Agonists (arachidonic acid, epinephrine, ATP and ADP) were used at EC50 and EC10 concentrations. Statistical analysis was performed using the MedCalc package. Results. After 72 hours of LCT, the activity of the TP receptor, α2-adrenergic receptor and purine P2-receptors of PLT decreased and reached the level of hyporeactivity. Recovery of the activity of P2X1- and P2Y-receptors to the level of normoreactivity was registered after 5 days, while the activity of the α2-adrenergic receptor remained in the range of hyporeactivity. On day 7, α2-adrenergic receptor and P2X1-receptor hyperreactivity developed and P2Yreceptor normoreactivity remained. The effectiveness of compensatory reactions of PLT aimed at limiting hematuria depended on the synergism of functionally active receptors. Conclusion. In women with nephrolithiasis during the administration of non-selective NSAIDs, the spontaneous increase in α2- adrenoreceptor activity is indicative of the lability of the sympathoadrenal system caused by the trafficking of stones in the urinary tract. The limitation of hematuria observed in this case is associated with increased proaggregation activity of platelet hemostasis due to synergism of α2-adrenoreceptor and P2-receptors.

The Effect of Nonsteroidal Anti-inflammatory Drugs and Selective COX-2 Inhibitors on Bone Healing.

A recently published study, "Risk of Nonunion With Nonselective NSAIDs, COX-2 Inhibitors, and Opioids" by George et al (J Bone Joint Surg Am. 2020;102:1230-1238), assesses whether the use of nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), selective cyclooxygenase 2 (COX-2) enzyme inhibitors, or opioids was associated with a risk of long bone fracture nonunion in Optum's deidentified private health database. This review analyzes the study, including strengths, weaknesses, and areas for future research. The study found an association between COX-2 inhibitor and opioid use with fracture nonunion but not with nonselective NSAID use. Although the literature on this topic is varied, these results are at least partially aligned with several animal studies that show COX-2 inhibitors to be associated with fracture nonunion. The George et al study design has several important limitations, indicating that further research is needed on this topic.

Practice Advisory on the Appropriate Use of NSAIDs in Primary Care.

Cyclo-oxygenase (COX)-2 selective and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) are important in managing acute and chronic pain secondary to inflammation. As a greater understanding of the risks of gastrointestinal (GI), cardiovascular (CV) and renal events with NSAIDs use has emerged, guidelines have evolved to reflect differences in risks among NSAIDs. Updated guidelines have yet to reflect new evidence from recent trials which showed similar CV event rates with celecoxib compared to naproxen and ibuprofen, and significantly better GI tolerability for celecoxib. This practice advisory paper aims to present consensus statements and associated guidance regarding appropriate NSAID use based on a review of current evidence by a multidisciplinary group of expert clinicians. This paper is especially intended to guide primary care practitioners within Asia in the appropriate use of NSAIDs in primary care. Following a literature review, group members used a modified Delphi consensus process to determine agreement with selected recommendations. Agreement with a statement by 75% of total voting members was defined a priori as consensus. For low GI risk patients, any nonselective NSAID plus proton pump inhibitor (PPI) or celecoxib alone is acceptable treatment when CV risk is low; for high CV risk patients, low-dose celecoxib or naproxen plus PPI is appropriate. For high GI risk patients, celecoxib plus PPI is acceptable for low CV risk patients; low-dose celecoxib plus PPI is appropriate for high CV risk patients, with the alternative to avoid NSAIDs and consider opioids instead. Appropriate NSAID prescription assumes that the patient has normal renal function at commencement, with ongoing monitoring recommended. In conclusion, appropriate NSAID use requires consideration of all risks.

A narrative review of the cardiovascular risks associated with concomitant aspirin and NSAID use.

The concomitant use of low-dose aspirin for cardioprotection and non-steroidal anti-inflammatory agents for pain relief is prevalent, particularly in the elderly for whom cardiovascular disease and pain are common co-morbidities. Non-selective non-steroidal anti-inflammatory drugs (NSAIDs) are known to interfere with the antiplatelet effect of aspirin through competitive binding with COX-1. While the clinical significance of this interference is still unclear, this review sought to assess the body of literature which has evaluated the potential attenuation of the anti-platelet effect of aspirin when dosed concomitantly with an NSAID. This review supports that the pharmacodynamic interaction between aspirin and non-selective NSAIDs occurs, but finds that the interaction varies amongst agents, and is highly dependent on numerous factors including: dose timing, dose of aspirin, and dose of the NSAID in question. Recent findings suggest that patient factors, such as body weight may also be indicators of aspirin's cardiovascular effectiveness. Ultimately, the clinical decision making for concomitant NSAID and low-dose aspirin regimens remains at the patient level.

Prescription of analgesics in orthopaedic outpatient department at a tertiary health care facility

The objective of the present prospective cross sectional descriptive study was to evaluate the prescribing pattern of analgesic drug by orthopaedic surgeons in outdoor patients. This study was conducted in the orthopaedic outpatient department (OPD) of the Department of Orthopaedics, Border Guard Hospital, Pilkhana, Dhaka for six months period from January 2016 to June 2016. Randomly selected 324 prescriptions were collected from the attending patients on OPD and analyzed. The details of prescribed drugs, various analgesics, monotherapy or combined therapy and use of generic name were analyzed. Among the 324 study prescriptions, males and females were 63.9% and 36.1%, respectively. Majority of patients (80.8%) were within 31-60 years of age. Different classes of drugs were prescribed: non-selective non-steroidal anti-inflammatory drugs (NSAIDs) use was 45.2%, selective NSAIDs 2.9%, opioid analgesics 7.3%, H2 blockers 13.6%, proton pump inhibitors 17.1%, muscle relaxants 4.0%, benzodiazepines 8.1%, and other adjuvants 1.9%. Among individual analgesics: diclofenac 23.5%, aceclofenac 6.0%, ketorolac 6.9%, naproxane 10.8%, ibuprofen 3.7%, indomethacin 3.5%, etoricoxib 6.2%, tramadol 15.4% and paracetamol 24.0% were used. Of the 324 patients, 33.6% received combination of analgesics: diclofenac+paracetamol 37.6%, aceclofenac+paracetamol 14.7%, ketorolac+ paracetamol 20.2%, tramadol+paracetamol 22.9% and diclofenac+tramadol 4.6%. Use of trade names was for 80.5% drugs and generic names for 19.5% drugs. NSAIDs were widely prescribed drugs. Use of selective was less comparing to non-selective NSAIDs. Tramadol was the most commonly prescribed opioid drug. Gastro protective agents were used with NSAIDs. Prescribers need to be encouraged to prescribe drugs only using generic names.Mediscope Vol. 4, No. 1: Jan 2017, Page 11-17

Analysis of risk factors for colonic diverticular bleeding and recurrence.

The increase in incidence of colonic diverticular bleeding is relative to an age-related rise in the incidence of colonic diverticulosis and use of antithrombotic medication. However, risk factors related to the onset, recurrence, and prophylaxis have not been established. Therefore, we aimed to determine risk factors for the onset and recurrence of colonic diverticular bleeding.An age- and sex-matched case-control study was performed to assess the risk factors for the onset of colonic diverticular bleeding. The distribution of diverticulosis, comorbidity, and medication were evaluated from medical records. We also assigned patients with a first-time bleeding into groups with and without rebleeding during follow-up to determine risk factors for recurrence.Bilateral colonic diverticulosis, nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin (LDA), and anticoagulants were significant risk factors for the onset of colonic diverticular bleeding on multivariate analysis. In contrast, the use of selective cyclooxygenase-2 (COX-2) inhibitor was not a risk factor for the onset. The incidence of bleeding in direct oral anticoagulant and warfarin users was not different between the 2 groups. The cumulative recurrence rate at 1 year was 15%. Recurrence rate was significantly higher in patients with a prior history of colonic diverticular bleeding than those without. Steroid use was associated with recurrence.Extensive distribution of diverticulosis and use of nonselective NSAIDs, LDA, and anticoagulants are regarded as risk factors for the onset of colonic diverticular bleeding. In addition, a prior history of colonic diverticular bleeding is related to the recurrence.

Naproxen and Diclofenac Attenuate Atorvastatin-induced Preconditioning of the Myocardium.

Statins reduce infarct size (IS) in ischemia-reperfusion injury of the myocardium. Inhibition of cyclooxygenase-2 (COX-2) attenuates this benefit. We investigated the effect of two widely used non-selective non-steroidal anti-inflammatory drugs (NSAIDs) with different degree of anti-COX-2 activity on atorvastatin-mediated preconditioning. Wistar rats received oral atorvastatin (10 mg∙kg-1∙day-1), naproxen (10 mg∙kg-1∙day-1), diclofenac (8 mg∙kg-1∙day-1), atorvastatin+naproxen, atorvastatin+diclofenac or water for three days. Hearts were then excised and perfused in the Langendorff system. Area at risk (AR) and IS were determined after 30 min of regional ischemia and 120 min of reperfusion. Atorvastatin reduced IS by 51.3% compared with controls (14.7 ± 3.9% vs. 30.2 ± 4.6% of the AR; P < 0.001). Naproxen and diclofenac alone did not alter IS compared to control. Diclofenac completely abrogated atorvastatin-mediated protection of the myocardium. Naproxen significantly attenuated but did not eliminate the IS reducing the effect of atorvastatin when compared with controls (P = 0.038). The difference in IS between the atorvastatin+naproxen group and the atorvastatin+diclofenac group showed a strong trend in reaching statistical significance (P = 0.058), but was not found to be significant. Our results suggest relatively small, but noticeable differences among non-selective NSAIDs in their potential to attenuate statin-mediated preconditioning.

ESC Congress 2015, London: hot lines truly hot?

ESC Congress 2015, London: hot lines truly hot?

Short-term use of glucocorticoids and risk of peptic ulcer bleeding: a nationwide population-based case-crossover study.

Controversy exists regarding glucocorticoids therapy and the risk of peptic ulcer bleeding (PUB). The present study was undertaken to determine whether short-term use ofglucocorticoids is associated with the occurrence of peptic ulcer bleeding. The records of adult patients hospitalised for newly diagnosed peptic ulcer bleeding from 2000 to 2012 were retrieved from the Taiwan National Health Insurance Research Database, a nationwide population-based registry system. The association between systemic glucocorticoids usage and peptic ulcer bleeding was determined with a conditional logistic regression model comparing cases and controls during time windows of 7, 14 and 28days using a case-crossover design. Of the 8894 enrolled patients, the adjusted self-matched odds ratios for peptic ulcer bleeding after exposure to the glucocorticoids were 1.37 (95% CI: 1.12-1.68, P=0.003) for the 7-day window, 1.66 (95% CI: 1.38-2.00, P<0.001) for the 14-day window and 1.84 (95% CI: 1.57-2.16, P<0.001) for the 28-day window. Moderate to high, but not low dose glucocorticoids (methylprednisolone <4mg/day or its equivalence) were associated with an increased risk of peptic ulcer bleeding. Concomitant use of a nonselective nonsteroidal anti-inflammatory drug (NSAID) or aspirin further elevated the risk. However, it does not eliminate the effect of underlying diseases flare-up that may have placed the patients at risk for peptic ulcer bleeding in this kind of study design. Short-term (7-28days) exposure to glucocorticoids is significantly associated with peptic ulcer bleeding; this risk seems dose-dependent and is higher when nonselective NSAIDs or aspirin are used concurrently.

COX-2 Selective Nonsteroidal Anti-inflammatory Drugs and Risk of Gastrointestinal Tract Complications and Myocardial Infarction

Instrumental variable analysis can estimate treatment effects in the presence of residual or unmeasured confounding. We compared ordinary least squares regression versus instrumental variable estimates of the effects of selective cyclooxygenase-2 inhibitors (COX-2s) relative to nonselective nonsteroidal anti-inflammatory drug (NSAID) prescriptions on incidence of upper gastrointestinal complications and myocardial infarction (MI). We sampled a cohort of 62,933 first-time users of COX-2s or nonselective NSAIDs older than 60 years in the Clinical Practice Research Datalink. The instruments were physicians' previous prescriptions of COX-2s or nonselective NSAIDs, which are surrogates for physician preferences. We estimated risk differences of incident upper gastrointestinal complications and MI within 180 days of first COX-2 versus nonselective NSAID prescription. Using ordinary least squares regression, adjusted for baseline confounders, we observed little association of COX-2 prescriptions with incident upper gastrointestinal complications (risk difference = -0.08 [95% confidence interval = -0.20 to 0.04]) or MI (0.06 [-0.06 to 0.17]) per 100 patients treated. Our adjusted instrumental variable results suggested 0.46 per 100 (-0.15 to 1.07) fewer upper gastrointestinal complications and little difference in acute MIs (0.08 per 100 [-0.61 to 0.76]), within 180 days of being prescribed COX-2s. Estimates were more precise when we used 20 previous prescriptions; the instrumental variable analysis implied 0.74 (0.28 to 1.19) fewer MIs per 100 patients prescribed COX-2s. Using instrumental variable analysis, we found some evidence that COX-2 prescriptions reduced the risk of upper gastrointestinal complications, consistent with randomized controlled trials. Our results using multiple instruments suggest that COX-2s may have heterogeneous within-class effects on MI.

A pharmacist-led information technology intervention for medication errors (PINCER): a multicentre, cluster randomised, controlled trial and cost-effectiveness analysis

SummaryBackgroundMedication errors are common in primary care and are associated with considerable risk of patient harm. We tested whether a pharmacist-led, information technology-based intervention was more effective than simple feedback in reducing the number of patients at risk of measures related to hazardous prescribing and inadequate blood-test monitoring of medicines 6 months after the intervention.MethodsIn this pragmatic, cluster randomised trial general practices in the UK were stratified by research site and list size, and randomly assigned by a web-based randomisation service in block sizes of two or four to one of two groups. The practices were allocated to either computer-generated simple feedback for at-risk patients (control) or a pharmacist-led information technology intervention (PINCER), composed of feedback, educational outreach, and dedicated support. The allocation was masked to general practices, patients, pharmacists, researchers, and statisticians. Primary outcomes were the proportions of patients at 6 months after the intervention who had had any of three clinically important errors: non-selective non-steroidal anti-inflammatory drugs (NSAIDs) prescribed to those with a history of peptic ulcer without co-prescription of a proton-pump inhibitor; β blockers prescribed to those with a history of asthma; long-term prescription of angiotensin converting enzyme (ACE) inhibitor or loop diuretics to those 75 years or older without assessment of urea and electrolytes in the preceding 15 months. The cost per error avoided was estimated by incremental cost-effectiveness analysis. This study is registered with Controlled-Trials.com, number ISRCTN21785299.Findings72 general practices with a combined list size of 480 942 patients were randomised. At 6 months' follow-up, patients in the PINCER group were significantly less likely to have been prescribed a non-selective NSAID if they had a history of peptic ulcer without gastroprotection (OR 0·58, 95% CI 0·38–0·89); a β blocker if they had asthma (0·73, 0·58–0·91); or an ACE inhibitor or loop diuretic without appropriate monitoring (0·51, 0·34–0·78). PINCER has a 95% probability of being cost effective if the decision-maker's ceiling willingness to pay reaches £75 per error avoided at 6 months.InterpretationThe PINCER intervention is an effective method for reducing a range of medication errors in general practices with computerised clinical records.FundingPatient Safety Research Portfolio, Department of Health, England.

Non-steroidal anti-inflammatory drug use and risk of atrial fibrillation or flutter: population based case-control study

Objectives To examine the risk of atrial fibrillation or flutter associated with use of non-selective non-steroidal anti-inflammatory drugs (NSAIDs) or selective cyclo-oxygenase (COX) 2 inhibitors. Design Population based case-control study...

Non‐steroidal anti‐inflammatory drug use and risk of venous thromboembolism

The association between the use of non-selective non-steroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2-selective inhibitors (COX2Is) and the risk of venous thromboembolism (VTE) remains unclear. To examine this association. We conducted a population-based case-control study in northern Denmark (population of 1.7 million). Using the National Patient Registry, we identified patients with a first hospital VTE diagnosis during 1999-2006 (n = 8368) and their comorbidities. For each case, we selected 10 controls (n = 82, 218) matched by age and sex. From the prescription database, we ascertained the use of NSAIDs at the time of diagnosis (current use) or before (recent use), and comedications. Current use was further classified as new use (first-ever prescription redemption within 60 days before diagnosis date) or long-term use. We used odds ratios from a logistic regression model to estimate incidence rate ratios (IRRs) with 95% confidence intervals (CIs). As compared with no use, the adjusted IRR associating current non-selective NSAID use with VTE was 2.51 (95% CI 2.29-2.76), and that for current COX2I use was 2.19 (95% CI 1.99-2.41). Recent users had substantially smaller increases than current users. The adjusted IRRs among long-term users were 2.06 for non-selective NSAIDs (95% CI 1.85-2.29) and 1.92 for COX2Is (95% CI 1.72-2.15). Similarly increased risks were found for unprovoked VTE (occurrence in the absence of pregnancy, cancer, major trauma, fracture or surgery within 3 months preceding the VTE), deep vein thrombosis, pulmonary embolism, and individual NSAIDs. The use of non-selective NSAIDs or COX2Is was associated with a two-fold or more increased risk of VTE.

Gastrointestinal tolerability of NSAIDs in elderly patients: a pooled analysis of 21 randomized clinical trials with celecoxib and nonselective NSAIDs

Background:Gastrointestinal (GI) tolerability is an important treatment consideration for physicians when choosing a nonselective nonsteroidal anti-inflammatory drug (NSAID) for their elderly arthritis patients. The objective of this study was to compare the GI tolerability of the cyclooxygenase-2 selective NSAID celecoxib and nonselective NSAIDs in elderly patients with arthritis aged 65 years or older.Methods:This was a retrospective, pooled analysis of patients aged 65 years or older with osteoarthritis (OA), rheumatoid arthritis (RA), or ankylosing spondylitis (AS) from randomized, parallel-group trials. Selected trials had a duration of ≥2 weeks and at least one celecoxib 200–400 mg/day and one nonselective NSAID (naproxen, ibuprofen, or diclofenac) arm. Patient-level data from the safety populations of the trials were pooled. Analysis included the combined incidence of the GI intolerability adverse events (AEs) (abdominal pain, constipation, diarrhea, dyspepsia, flatulence, nausea) and incidence and time to trial discontinuation due to these intolerability AEs.Results:A total of 21 trials were selected involving 9461 elderly patients (mean age 71.9 years). Of these, 5872 received celecoxib, 1104 naproxen, 151 ibuprofen, and 2334 diclofenac. The combined incidence of GI intolerability AEs were reported by significantly fewer patients treated with celecoxib (16.7%) than naproxen (29.4%; p < 0.0001), ibuprofen (26.5%; p = 0.0016), or diclofenac (21.0%; p < 0.0001). The discontinuation rate due to GI intolerability AEs was significantly lower for celecoxib (4.0%) versus naproxen (8.1%; p < 0.0001) and ibuprofen (7.3%; p < 0.05), but not diclofenac (4.2%; p = 0.75).Conclusions:Among elderly arthritis patients, the incidence of GI intolerability AEs was lower with celecoxib than with naproxen, ibuprofen, or diclofenac. Fewer elderly patients discontinued due to GI intolerability AEs with celecoxib than with either naproxen or ibuprofen.

Nonsteroidal Antiinflammatory Drug Use and Cardiovascular Risks After Coronary Stent Implantation

To determine whether use of nonselective nonsteroidal antiinflammatory drugs (NSAIDs) or cyclooxygenase-2 (COX-2)-selective inhibitors in patients with coronary stents increased the 3-year rate of major adverse cardiovascular events (MACE). Population-based cohort study. The Danish National Patient Registry, the Western Denmark Heart Registry, the Danish Nationwide Prescription Database, the Danish Civil Registration System, and the National Registry of Causes of Deaths. A total of 13,001 patients who underwent first-ever percutaneous coronary intervention with stent implantation between January 1, 2002, and June 30, 2005. All patients were followed for 3 years after stent implantation for MACE, defined as the first occurrence of myocardial infarction, stent thrombosis, target-lesion revascularization, or cardiac death. Patients' comorbidities were identified from the hospital registries; time-varying use of NSAIDs and concomitant drugs was determined from the Danish Nationwide Prescription Database. For each clinical outcome (MACE), the 3-year risk was computed. We used Cox proportional-hazards regression analysis to compute hazard ratios (HRs) as a measure of relative risk, controlling for potential confounders. During the follow-up period, 5407 patients (41.6%) redeemed at least one NSAID prescription. There were 686 hospitalizations for myocardial infarction (5.3% of patients), 146 for stent thrombosis (1.1%), and 1091 for target-lesion revascularization (8.4%). A total of 1220 patients (9.4%) died during the follow-up period; 637 (4.9%) died of cardiac causes. Compared with no NSAID use, the adjusted HR for MACE was 1.04 (95% confidence interval [CI] 0.83-1.31) for nonselective NSAID use and 1.00 (95% CI 0.81-1.25) for COX-2 inhibitor use. Use of nonselective NSAIDs or COX-2 inhibitors was not associated with an increased rate of MACE in patients with coronary stents. However, we cannot rule out small risks associated with individual NSAIDs.

Risk of hyperkalemia associated with selective COX‐2 inhibitors

Selective cyclooxygenase-2 (COX-2) inhibitors have been linked to cardiac death. The mechanism for this adverse effect appears to be by ischemic insult; however another mechanism could involve hyperkalemia. The objective of this study was to determine the effects of selective COX-2 inhibitors and non-selective nonsteroidal anti-inflammatory drugs (NSAIDs) on serum potassium concentration and the electrocardiogram. A retrospective cohort study was conducted using propensity score matching of patients from an inner-city academic medical center at Indianapolis, Indiana. Two hundred and two patients prescribed selective COX-2 inhibitors were matched to 202 patients prescribed non-selective NSAIDs using propensity scores methods. Outcomes included change in serum potassium concentration from baseline and the risk of an abnormal electrocardiogram. Compared to patients prescribed non-selective NSAIDs, those prescribed a selective COX-2 inhibitor had a higher risk of serum potassium increase greater than 5 mEq/L (OR, 2.56; 95%CI, 1.03-6.36). However, patients prescribed selective COX-2 inhibitors had no greater risk of electrocardiogram abnormality (OR, 1.16; 95%CI, 0.74-1.82). Selective COX-2 inhibitors may have a greater risk of hyperkalemia than non-selective NSAIDs. This study was exploratory with small numbers of patients. Further studies are needed to confirm these results and any association with cardiovascular events.

Analgesic use and the risk for progression of chronic kidney disease

The chronic effect of various analgesics on the progression of chronic kidney disease (CKD) is inconclusive. There is also lack of information on the renal safety of selective cyclooxygenase-2 (COX-2) inhibitors. This study aimed to clarify the renal risk of analgesic use in CKD patients. A cohort study using a nationally representative database randomly sampled from National Health Insurance (NHI) enrollees was performed. The study population included a total of 19,163 newly diagnosed CKD patients. Clinical conditions were defined by diagnostic codes and exposure information on analgesics was derived from service claims. Cox proportional hazard model was used to assess the association between analgesic use and the risk of progression to end stage renal disease (ESRD). CKD patients using acetaminophen, aspirin, and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) had an increased risk for ESRD with multivariable-adjusted HRs (95%CIs) of 2.92 (2.47-3.45), 1.96 (1.62-2.36), and 1.56 (1.32-1.85), respectively. The trends toward higher risk with increasing exposure dose were significant for all classes of analgesics (all P for trend < 0.001). Among COX-2 inhibitors, only rofecoxib, but not celecoxib, shows a significant risk association with ESRD (HR = 1.98; 95%CI, 1.15-3.40). Our data indicated exacerbating effects of acetaminophen, aspirin, and non-selective NSAIDs on CKD in a dose-dependent manner. For COX-2 inhibitors, only rofecoxib showed an increased risk for ESRD. Although the possibility of residual confounding cannot be completely ruled out, given the common use of analgesics, the possible relation suggested by this study warrants further investigation.

Genetic Polymorphisms and the Cardiovascular Risk of Non-Steroidal Anti-Inflammatory Drugs

The cardiovascular safety of cyclooxygenase-2-selective (coxibs) and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) is of concern, although most users remain free of adverse outcomes. A gene-drug interaction could modulate this cardiovascular risk through prostaglandin synthesis or inflammatory pathways. From an existing acute coronary syndrome cohort (Recurrence and Inflammation in the Acute Coronary Syndromes Study) (n = 1,210), a case-only study was performed by identifying 115 patients exposed to NSAIDs (rofecoxib [n = 43], celecoxib [n = 49], or nonselective NSAIDs [n = 23]) and 345 unexposed patients matched for age, gender, and hospital center. These patients were genotyped for 115 candidate single-nucleotide polymorphisms (SNPs). Statistically significant associations between NSAID exposure and 9 SNPs in 6 genes were observed. Analyzing patients exposed only to coxibs and their matched unexposed cases, significant associations remained for 5 SNPs at 4 loci (prostaglandin-endoperoxide synthase-1 [PTGS1], chromosome 9p21.3, C-reactive protein [CRP], and klotho [KL]). Two independent SNPs from the PTGS1 gene gave similar results under a recessive model, with odds ratios for the association with NSAID exposure of 6.94 (95% confidence interval 1.35 to 35.65, p = 0.016) and 7.11 (95% confidence interval 1.38 to 36.74, p = 0.033). A significant association was also observed for a SNP in the CRP gene (rs1205) (additive odds ratio 1.64, 95% confidence interval 1.18 to 2.27, p = 0.003). In conclusion, these findings suggest that genetic variability may contribute to the susceptibility for acute coronary syndromes observed in some NSAID users. In particular, genetic polymorphisms in the PTGS1 and CRP genes appear to be candidates for a possible gene-drug interaction influencing the acute coronary risk associated with NSAID use, but these findings will require confirmation in larger cohorts.

Efficacy and Safety of Celecoxib in the Treatment of Acute Pain due to Ankle Sprain in a Latin American and Middle Eastern Population

Ankle sprains are common acute soft-tissue injuries. This 7-day open-label, multicentre, randomized study compared the efficacy and safety of celecoxib with non-selective non-steroidal anti-inflammatory drugs (NSAIDs) in treating acute ankle sprain with moderate-to-severe ankle pain in 278 patients. Patients received either celecoxib (400 mg loading dose followed by 200 mg twice daily) or standard doses of non-selective NSAIDs. The primary endpoint was a change in the patient's assessment of ankle pain on a 0 mm (no pain) - 100 mm (worst possible pain) visual analogue scale (VAS) at day 3 compared with baseline. From a baseline of 73 mm, mean VAS pain scores decreased to 29 and 32 mm in the celecoxib and non-selective NSAID groups, respectively. The lower limit of the 95% confidence interval for the treatment difference with regard to change from baseline was greater than the pre-established non-inferiority margin of -10 mm. Using an initial loading dose, celecoxib was at least as efficacious as non-selective NSAIDs in treating acute pain due to ankle sprain.