What is the drug of choice in a patient who is taking aspirin for secondary prevention of stroke? Ibuprofen? Celecoxib? Other? Plus 6 more questions on NSAID use in primary care.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are mainstays for managing acute and chronic pain secondary to inflammation; however, the gastrointestinal (GI), cardiovascular (CV), and renal risks associated with the class require careful patient selection. An international group of experts in 2020 released a practice advisory published in the Journal of Pain Research, which summarizes current evidence and provides updated guidance to primary care physicians on the use of NSAIDs for pain, with an emphasis on CV, GI, and renal safety.
What does the 2020 practice advisory along with previous research recommend regarding the appropriate use of NSAIDs in primary care? Take the 7-question quiz below to find out.
1. All of the above patients are considered to be high risk for NSAID-associated adverse events except which one?
Answer: B. A patient aged 45 years who is obese. In the 2020 practice advisory, authors advised using NSAIDs with caution in patients with high GI, CV, and renal risk, including patients aged ≥65 years who are taking aspirin, patients aged >75 years with a history of ACS, and patients who are taking an ACE inhibitor.1
Answer: D. Diclofenac. Among nonselective NSAIDs, diclofenac has the least risk of GI side effects. However, it carries the highest risk of CV events and is associated with increased risk of hepatic impairment.1
3. Which of the above is a drug of choice in a patient who is taking aspirin for secondary prevention of stroke?
Answer: A. Celecoxib. In patients who are taking aspirin for secondary prevention of stroke or coronary thrombosis, selective cyclo-oxygenase (COX)-2 inhibitors are the drug of choice, due to potential COX-1 inhibitors drug-drug interactions.1 In particular, chronic use of ibuprofen combined with daily aspirin may affect platelet function and decrease the efficacy of aspirin in preventing CV events.2
4. A 65-year-old patient with osteoarthritis requires NSAIDs for pain control. The patient has a history of ACS, an eGFR of 100 mL/min, and low GI risk. Which of the above is the preferred NSAID in this patient?
Answer: D. Both A and C. According to the 2020 practice advisory, for a patient who has a history of ACS (high CV risk) but who has normal renal function and low GI risk, the preferred NSAIDs are low-dose celecoxib (200 mg/day) or naproxen plus a proton pump inhibitor for GI protection.1
5. Which of the above drugs is available in the US and is associated with fewer GI adverse events than ibuprofen?
Answer: D. Celecoxib. COX-2 selective inhibitors are better than nonselective NSAIDs for the prevention of both upper and lower GI adverse events. Celecoxib is the only selective COX-2 inhibitor that is FDA-approved in the US.1
6. Which of the above has been linked to an increased risk for major toxicity associated with NSAID use?
Answer: C. Tobacco use. In a 2019 analysis, researchers used data from the PRECISION trial to evaluate a toxicity score for predicting 1-year risk of major toxicity among users of celecoxib, naproxen, or ibuprofen. Major toxicity included major adverse CV events, acute kidney injury, significant GI events, and death. The following were significantly associated with major toxicity: Age, male sex, history of CVD, hypertension, diabetes, tobacco use, elevated serum creatinine, hematocrit level, type of arthritis.3
7. True or false? Nonselective NSAIDs and COX-2 selective NSAIDs are both associated with increased risk of adverse renal events.
Answer: A. True. According to a 2019 analysis, both nonselective and COX-2 selective NSAIDs are associated with increased risk of adverse renal events. However, renal risk may vary by individual NSAID.3 A 2017 meta-analysis found that NSAIDs with high COX-2 selectivity were associated with lower odds of acute kidney injury vs those with lower COX-2 selectivity.4
1. Ho KY, Cardosa MS, Chaiamnuay S, et al. Practice advisory on the appropriate use of NSAIDs in primary care. J Pain Res. 2020;13:1925-1939.
2. Moore N, Pollack C, Butkerait P. Adverse drug reactions and drug-drug interactions with over-the-counter NSAIDs. Ther Clin Risk Manag. 2015;11:1061-1075
3. Solomon DH, Shao M, Wolski K, Nissen S, Husni ME, Paynter N. Derivation and validation of a major toxicity risk score among nonsteroidal antiinflammatory drug users based on data from a randomized controlled trial. Arthritis Rheumatol. 2019;71:1225-1231.
4. Zhang X, Donnan PT, Bell S, Guthrie B. Non-steroidal anti-inflammatory drug induced acute kidney injury in the community dwelling general population and people with chronic kidney disease: systematic review and meta-analysis. BMC Nephrol. 2017;18:256.