Effectiveness and safety of non-steroidal anti-inflammatory drugs and opioid treatment for knee and hip osteoarthritis: network meta-analysis

OBJECTIVE: To assess the effectiveness and safety of different preparations and doses of non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and paracetamol for knee and hip osteoarthritis pain and physical function to enable effective and safe use of these drugs at their lowest possible dose. DESIGN: Systematic review and network meta-analysis of randomised trials. DATA SOURCES: Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, regulatory agency websites, and ClinicalTrials.gov from inception to 28 June 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised trials published in English with ≥100 patients per group that evaluated NSAIDs, opioids, or paracetamol (acetaminophen) to treat osteoarthritis. OUTCOMES AND MEASURES: The prespecified primary outcome was pain. Physical function and safety outcomes were also assessed. REVIEW METHODS: Two reviewers independently extracted outcomes data and evaluated the risk of bias of included trials. Bayesian random effects models were used for network meta-analysis of all analyses. Effect estimates are comparisons between active treatments and oral placebo. RESULTS: 192 trials comprising 102 829 participants examined 90 different active preparations or doses (68 for NSAIDs, 19 for opioids, and three for paracetamol). Five oral preparations (diclofenac 150 mg/day, etoricoxib 60 and 90 mg/day, and rofecoxib 25 and 50 mg/day) had ≥99% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. Topical diclofenac (70-81 and 140-160 mg/day) had ≥92.3% probability, and all opioids had ≤53% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. 18.5%, 0%, and 83.3% of the oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of dropouts due to adverse events. 29.8%, 0%, and 89.5% of oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of any adverse event. Oxymorphone 80 mg/day had the highest risk of dropouts due to adverse events (51%) and any adverse event (88%). CONCLUSIONS: Etoricoxib 60 mg/day and diclofenac 150 mg/day seem to be the most effective oral NSAIDs for pain and function in patients with osteoarthritis. However, these treatments are probably not appropriate for patients with comorbidities or for long term use because of the slight increase in the risk of adverse events. Additionally, an increased risk of dropping out due to adverse events was found for diclofenac 150 mg/day. Topical diclofenac 70-81 mg/day seems to be effective and generally safer because of reduced systemic exposure and lower dose, and should be considered as first line pharmacological treatment for knee osteoarthritis. The clinical benefit of opioid treatment, regardless of preparation or dose, does not outweigh the harm it might cause in patients with osteoarthritis. SYSTEMATIC REVIEW REGISTRATION: PROSPERO number CRD42020213656

Accuracy of 64-slice CT angiography for the detection of functionally relevant coronary stenoses as assessed with myocardial perfusion SPECT

PURPOSE: CT angiography (CTA) offers a valuable alternative for the diagnosis of CAD but its value in the detection of functionally relevant coronary stenoses remains uncertain. We prospectively compared the accuracy of 64-slice CTA with that of myocardial perfusion imaging (MPI) using (99m)Tc-tetrofosmin-SPECT as the gold standard for the detection of functionally relevant coronary artery disease (CAD). METHODS: MPI and 64-slice CT were performed in 100 consecutive patients. CTA lesions were analysed quantitatively and area stenoses > or =50% and > or =75% were compared with the MPI findings. RESULTS: In 23 patients, MPI perfusion defects were found (12 reversible, 13 fixed). A total of 399 coronary arteries and 1,386 segments was analysed. Eighty-four segments (6.1%) in 23 coronary arteries (5.8%) of nine patients (9.0%) were excluded owing to insufficient image quality. In the remaining 1,302 segments, quantitative CTA revealed stenoses > or =50% in 57 of 376 coronary arteries (15.2%) and stenoses > or =75% in 32 (8.5%) coronary arteries. Using a cut-off at > or =75% area stenosis, CTA yielded the following sensitivity, specificity, negative (NPV) and positive predictive value (PPV), and accuracy for the detection of any (fixed and reversible) MPI defect: by patient, 75%, 90%, 93%, 68% and 87%, respectively; by artery, 76%, 95%, 99%, 50% and 94%, respectively. CONCLUSION: Sixty-four-slice CTA is a reliable tool to rule out functionally relevant CAD in a non-selected population with an intermediate pretest likelihood of disease. However, an abnormal CTA is a poor predictor of ischaemia