Нестероидные противовоспалительные препараты: повреждающее действие на слизистую оболочку желудка и способы защиты от их ульцерогенного влияния

NSAIDs, Risks, and Gastroprotective Strategies: Current Status and Future

Clinical trial data have prompted questions about the degree to which patients and their physicians should consider an increased risk of cardiovascular or cerebrovascular events when selecting medications for pain relief. Since the 2005 publication of a Science Advisory on the use of nonsteroidal antiinflammatory drugs (NSAIDs) by the American Heart Association,1 several important events have occurred that have served as the catalyst for this update for clinicians. (1) Additional data from randomized controlled trials of cyclooxygenase (COX)-2–selective agents have been reported and summarized in meta-analyses, which has reinforced the concern about cardiovascular events with COX-2 inhibitors (coxibs; Figure 1). (2) Several reports have appeared that have identified an increased risk of cardiovascular events even with the nonselective NSAIDs, which has raised concern about the use of those agents as well (Table). (3) Regulatory authorities in several regions of the world have introduced warning statements and advisories to both healthcare professionals and the lay public about the use of various NSAIDs (Figures 2 and 3⇓). Figure 1. Comparison of effects of different selective COX-2 inhibitors vs placebo on myocardial infarction. Event numbers and person-years of exposure, with corresponding mean annual event rates in parentheses, are presented for patients allocated to selective COX-2 inhibitor or placebo. Event rate ratios for pooled data with 95% CIs are indicated by a diamond; rate ratios for individual selective COX-2 inhibitors, with 99% CIs, are indicated by a square and horizontal line. Diamonds to the right of the solid line indicate hazard with a selective COX-2 inhibitor compared with placebo. As noted, there was a significant increase in the rate ratio for myocardial infarction with COX-2 inhibitors compared with placebo. Similar analyses (data not shown) include rate ratios of 1.42 (1.13 to 1.78; P =0.003) for vascular events, 1.02 (0.71 to 1.47; P …

Celecoxib Plus Aspirin Versus Naproxen and Lansoprazole Plus Aspirin: A Randomized, Double-Blind, Endoscopic Trial

Do non-steroidal anti-inflammatory drugs cause osteoarthritis progression, a systematic review and meta analysis

Reducing the Gastrointestinal Risks of Low-Dose Aspirin

NSAID Use and Progression of Chronic Kidney Disease

Consensus Development Conference on the Use of Nonsteroidal Anti-Inflammatory Agents, Including Cyclooxygenase-2 Enzyme Inhibitors and Aspirin

Lower GI bleeding risk of nonsteroidal anti-inflammatory drugs and antiplatelet drug use alone and the effect of combined therapy

ABSTRACTPurpose: The purpose of this article is to review the current guidelines for Enhanced Recovery After Surgery (ERAS) following colorectal surgery with nonsteroidal anti-inflammatory drugs (NSAID) use and its association with anastomotic leaks.Method: A Medline literature search was conducted with search terms colorectal surgery, nonsteroidal anti-inflammatory drugs, and anastomotic leaks. Seventeen relevant articles served as the basis for this clinical review. This group was further refined to analyze selective vs non-selective NSAIDs to assess the overall risk of anastomotic leaks.Results: The use of NSAIDs postoperatively was associated with an overall increased risk of anastomotic leaks. This risk varied with the type of NSAID taken for pain control: selective vs non-selective. Non-selective NSAIDs had an increased risk while selective NSAIDs appeared safe. Conclusion: NSAIDs are an important aspect of the ERAS guidelines to improve patient outcomes after surgery. They provide an alternative option for pain control for opioid medications and their known side effects. Recent literature varies in the risk profiles and safety of different classes of NSAIDs. Postoperative use of NSAIDs, particularly diclofenac, is associated with increased risk for anastomotic leak following colorectal surgery.Keywords: Colorectal surgery, nonsteroidal anti-inflammatory drugs, anastomotic leaks.

Chronic back pain is an important health problem. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat people with low back pain, especially people with acute back pain. Short term NSAID use is also recommended for pain relief in people with chronic back pain. Two types of NSAIDs are available and used to treat back pain: non-selective NSAIDs and selective COX-2 NSAIDs. In 2008, a Cochrane review identified a small but significant effect from NSAIDs compared to placebo in people with chronic back pain. This is an update of the Cochrane review published in 2008 and focuses on people with chronic low back pain. To determine if NSAIDs are more efficacious than various comparison treatments for non-specific chronic low back pain and if so, which type of NSAID is most efficacious. We searched CENTRAL, MEDLINE, EMBASE, PubMed and two clinical trials registry databases up to 24 June 2015 for randomized controlled trials (RCTs) published in English, German or Dutch. We also screened references cited in relevant reviews. We included RCTs (double-blind and single-blind) of NSAIDs used to treat people with chronic low back pain. Two review authors independently screened trials for inclusion in this Cochrane review according to the inclusion criteria. One review author extracted the data, and a second review author checked the data. Two review authors independently evaluated the risk of bias of all included trials. If data were clinically homogeneous, we performed a meta-analysis and assessed the quality of evidence using the GRADE approach. We included 13 trials in this Cochrane review. Ten studies were at 'low' risk of bias. Six studies compared NSAIDs with placebo, and included 1354 participants in total. There is low quality evidence that NSAIDs are more effective than placebo, with a mean difference in pain intensity score from baseline of -3.30 (95% CI -5.33 to -1.27) on a 0 to 100 visual analogue scale (VAS) with a median follow-up of 56 days (interquartile range (IQR) 13 to 91 days). Four studies measured disability using the Roland Morris Disability Questionnaire. There is low quality evidence that NSAIDs are more effective than placebo on disability, with a mean difference from baseline of -0.85 (95% CI -1.30 to -0.40) on a scale from 0 to 24 with a median follow-up of 84 days (IQR 42 to 105 days). All six placebo controlled studies also reported adverse events, and suggested that adverse events are not statistically significant more frequent in participants using NSAIDs compared to placebo (RR 1.04, 95% CI 0.92 to 1.17). Due to the relatively small sample size and relatively short follow-up in most included trials, it is likely that the proportion of patients experiencing an adverse event is underestimated.Two studies compared different types of non-selective NSAIDs, namely ibuprofen versus diclofenac and piroxicam versus indomethacin. The trials did not find any differences between these NSAID types, but both trials had small sample sizes. One trial reported no differences in pain intensity between treatment groups that used selective or non-selective NSAIDs. One other trial compared diflunisal with paracetamol and showed no difference in improvement from baseline on pain intensity score. One trial showed a better global improvement in favour of celecoxib versus tramadol.One included trial compared NSAIDs with 'home-based exercise'. Disability improved more in participants who did exercises versus participants receiving NSAIDs, but pain scores were similar. Six of the 13 included RCTs showed that NSAIDs are more effective than placebo regarding pain intensity. NSAIDs are slightly more effective than placebo regarding disability. However, the magnitude of the effects is small, and the level of evidence was low. When we only included RCTs at low risk of bias, differences in effect between NSAIDs and placebo were reduced. We identified no difference in efficacy between different NSAID types, including selective versus non-selective NSAIDs. Due to inclusion of RCTs only, the relatively small sample sizes and relatively short follow-up in most included trials, we cannot make firm statements about the occurrence of adverse events or whether NSAIDs are safe for long-term use.

Evidence from some studies suggest that osteoarthritis (OA) patients are often prescribed non-steroidal anti-inflammatory drugs (NSAIDs) that are not in accordance with their cardiovascular (CV) or gastrointestinal (GI) risk profiles. However, no such study has been carried out in the United States. Therefore, we sought to examine the prevalence and predictors of potentially inappropriate NSAIDs use in older adults (age > 65) with OA using machine learning with real-world data from Optum De-identified Clinformatics® Data Mart. We identified a retrospective cohort of eligible individuals using data from 2015 (baseline) and 2016 (follow-up). Potentially inappropriate NSAIDs use was identified using the type (COX-2 selective vs. non-selective) and length of NSAIDs use and an individual’s CV and GI risk. Predictors of potentially inappropriate NSAIDs use were identified using eXtreme Gradient Boosting. Our study cohort comprised of 44,990 individuals (mean age 75.9 years). We found that 12.8% individuals had potentially inappropriate NSAIDs use, but the rate was disproportionately higher (44.5%) in individuals at low CV/high GI risk. Longer duration of NSAIDs use during baseline (AOR 1.02; 95% CI:1.02–1.02 for both non-selective and selective NSAIDs) was associated with a higher risk of potentially inappropriate NSAIDs use. Additionally, individuals with low CV/high GI (AOR 1.34; 95% CI:1.20–1.50) and high CV/low GI risk (AOR 1.61; 95% CI:1.34–1.93) were also more likely to have potentially inappropriate NSAIDs use. Heightened surveillance of older adults with OA requiring NSAIDs is warranted.

With the implementation of multimodal analgesia regimens in fast-track surgery programmes, non-steroidal anti-inflammatory drugs (NSAIDs) are being prescribed routinely. However, doubts have been raised concerning the safety of NSAIDs in terms of anastomotic healing. Data on patients who had undergone primary colorectal anastomosis at two teaching hospitals between January 2008 and December 2010 were analysed retrospectively. Exact use of NSAIDs was recorded. Rates of anastomotic leakage were compared between groups and corrected for known risk factors in both univariable and multivariable analyses. A total of 795 patients were divided into four groups according to NSAID use: no NSAIDs (471 patients), use of non-selective NSAIDs (201), use of selective cyclo-oxygenase (COX) 2 inhibitors (79), and use of both selective and non-selective NSAIDs (44). The overall leak rate was 9.9 per cent (10.0 per cent for right colonic, 8.7 per cent for left colonic and 12.4 per cent for rectal anastomoses). Known risk factors such as smoking and use of steroids were not significantly associated with anastomotic leakage. Stapled anastomosis was identified as an independent predictor of leakage in multivariable analysis (odds ratio (OR) 2.22, 95 per cent confidence interval 1.30 to 3.80; P = 0.003). Patients on NSAIDs had higher anastomotic leakage rates than those not on NSAIDs (13.2 versus 7.6 per cent; OR 1.84, 1.13 to 2.98; P = 0.010). This effect was mainly due to non-selective NSAIDs (14.5 per cent; OR 2.13, 1.24 to 3.65; P = 0.006), not selective COX-2 inhibitors (9 per cent; OR 1.16, 0.49 to 2.75; P = 0.741). The overall mortality rate was 4.2 per cent, with no significant difference between groups (P = 0.438). Non-selective NSAIDs may be associated with anastomotic leakage.

Despite growing evidence showing an increased risk of concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) and anticoagulants, few studies have investigated whether proton pump inhibitors can prevent gastrointestinal (GI) complications in patients receiving both NSAIDs and anticoagulants. We aimed to evaluate the risk of serious GI complications and the impact of GI preventive strategies on the concomitant use of NSAIDs and anticoagulants. Our nationwide cohort study using Korea's claims data included elderly patients (aged ≥65 years) who started anticoagulants and NSAIDs from 2016 to 2017. The outcome was serious GI complications defined as hospitalization or emergency department visits with GI bleeding or perforation. A Cox regression analysis was performed using time-dependent variables and propensity score matching. In total, 92,379 patients were identified. Compared with non-prophylaxis, proton pump inhibitors and selective cyclooxygenase-2 inhibitors were associated with a 64% [adjusted hazard ratio, 0.36 (95% confidence interval 0.25-0.53)] and 74% [adjusted hazard ratio, 0.26 (95% confidence interval 0.19-0.36)] lower risk of serious GI complications, respectively. Cyclooxygenase-2 inhibitor use was not different from the use of non-selective NSAIDs with proton pump inhibitors for the prevention of serious GI complications. H2-receptor antagonists did not reduce the risk of serious GI complications compared with non-prophylaxis during concomitant non-selective NSAID and anticoagulant therapy. Proton pump inhibitors or cyclooxygenase-2 inhibitors used as GI preventive strategies did not completely eliminate but lowered the risk of serious GI complications among elderly patients receiving both NSAIDs and anticoagulants.

Response

The cyclooxygenase-2 (COX-2) selective nonsteroidal antiinflammatory drugs (NSAIDs) celecoxib and rofecoxib (before its removal) are marketed as having fewer gastrointestinal (GI)-related complications than nonselective NSAIDs. However, adverse reaction data suggest that the use of COX-2 selective NSAIDs is associated with clinically significant GI events. To assess whether patients receiving celecoxib and rofecoxib have a greater underlying disease burden than patients prescribed nonselective NSAIDs. The study population consisted of members of 11 health plans, aged >34 years, with a pharmacy claim for celecoxib or rofecoxib or a nonselective NSAID dispensed between February 1, 1999, and July 31, 2001, who had been continuously enrolled for >364 days before the dispensing date. Celecoxib and rofecoxib patients were randomly selected without replacement from a pool of eligible users in each of the 30 months. Nonselective NSAID users were randomly chosen without replacement within each month on a 2:1 ratio to cases; they could be chosen in more than one month. Univariate analyses comparing 9000 cases and 18 000 controls were performed, followed by a multiple logistic regression analysis conditioned on time. Increasing age, treatment by a rheumatologist or an orthopedic specialist, treatment with a high number of different medications in the past year, treatment with oral corticosteroids in the past year, and having had a previous GI bleed increased the likelihood of receiving celecoxib or rofecoxib, whereas treatment with a high number of nonselective NSAID prescriptions in the past year decreased it. Treatment with a high number of different medications was a predictor of increased prevalence of underlying diabetes mellitus and cardiovascular disease. Patients having a greater underlying disease burden were more likely to receive COX-2 selective NSAIDs than nonselective ones. Paradoxically, patients at higher risk for cardiovascular disease were channeled toward treatment with COX-2 selective NSAIDs, many of which may confer an increased risk of acute myocardial infarction and other adverse cardiovascular outcomes.