Differences in cardiovascular safety with non‐steroidal anti‐inflammatory drug therapy—A nationwide study in patients with osteoarthritis

Abstract

Osteoarthritis (OA) and the non-steroidal anti-inflammatory drugs (NSAIDs) used to relieve OA-associated pain have been linked independently to increased cardiovascular risk. We examined the risk of cardiovascular events associated with NSAID use in patients with OA. We employed linked nationwide administrative registers to examine NSAID use between 1996 and 2015 by Danish patients with OA aged ≥18 years.Using adjusted Cox proportional hazard analyses, we calculated the risk of the composite outcome of cardiovascular death, non-fatal myocardial infarction and non-fatal ischaemic stroke/TIA, and of each outcome separately, up to 5 years after OA diagnosis. Of 533 502 patients included, 64.3% received NSAIDs and 38 226 (7.2%) experienced a cardiovascular event during follow-up. Compared with non-use, all NSAIDs were associated with increased risk of the composite outcome: hazard ratio (HR) for rofecoxib, 1.90 (95% confidence interval, 1.74-2.08); celecoxib, 1.47 (1.34-1.62); diclofenac, 1.44 (1.36-1.54); ibuprofen, 1.20 (1.15-1.25); and naproxen, 1.20 (1.04-1.39). Similar results were seen for each outcome separately. When celecoxib was used as reference, ibuprofen (HRs: 0.81 [CI: 0.74-0.90]) and naproxen (HRs: 0.81 [0.68-0.97]) exhibited a lower cardiovascular risk, even when low doses were compared. Low-dose naproxen and ibuprofen were associated with the lowest risks of the composite outcome compared to no NSAID use: HRs: 1.12 (1.07-1.19) and 1.16 (0.92-1.42), respectively. In patients with OA, we found significant differences in cardiovascular risk among NSAIDs. Naproxen and ibuprofen appeared to be safer compared to celecoxib, also when we examined equivalent low doses. In terms of cardiovascular safety, naproxen and ibuprofen, at the lowest effective doses, may be the preferred first choices among patients with OA needing pain relief.

Naproxen in the environment: its occurrence, toxicity to nontarget organisms and biodegradation

“…This has resulted in the occurrence of into the synovial fluid. It is the preferred drug for treating osteoarthritis in patients who are at a high cardiovascular risk because, unlike diclofenac and other NSAIDs including the selective ones, when it is used in high doses, it poses a lower vascular risk (Angiolillo and Weisman 2017;Barcella et al 2019). These advantages together with fact that naproxen can be purchased without a prescription translate into its popularity on the pharmaceutical market.…”

“…Naproxen, which is a bicyclic propionic acid derivative, is a widely known drug from the group of non-selective, nonsteroidal anti-inflammatory drugs (Dzionek et al 2018). Its mechanism of action is based on the inhibition of both cyclooxygenase isoforms that are involved in the synthesis of prostaglandins, prostacyclin and thromboxane from arachidonic acid (Angiolillo and Weisman 2017;Barcella et al 2019). The advantages of naproxen are its rapid absorption and its long duration of action, which result from its long biological half-life (approximately 13 h), and its ability to strongly bind to the plasma proteins.…”

NSAID-Induced Adverse Drug Reaction: Mechanism and Management

“…Of all patients who received treatment with NSAIDs, 7.2% experienced cardiovascular events during the treatment period. The use of ketorolac was also identified as increasing cases of acute myocardial infarction (AMI), followed by indomethacin, etoricoxib, rofecoxib, diclofenac (8,16) .…”

“…The extensive use of NSAIDs causes many problems, including gastrointestinal diseases (ranging from dyspepsia to ulcers), kidney, cardiovascular disorders, and hypersensitivity problems (1,2,5) . The prevalence of ADR due to NSAIDs is 22%, with a considerable risk of gastrointestinal diseases 1-5%, cardiovascular 7.2%, renal toxicities 1-5%, and hypersensitivity 0.6-5.7% (6)(7)(8)(9) . The literature search was carried out to update data about the NSAID class of drugs that commonly cause hospitals' problems globally.…”

A patient with osteoarthritis out of a doctor's field of vision: how should joint pain be controlled within the concept of responsible self-treatment?

“…В него входили 533 502 пациента, 64,3% из которых принимали разные НПВП, а у 38 226 был отмечен летальный исход, связанный с кардиоваскулярной патологией, нефатальный ИМ и/или инсульт. [74]. Кроме минимального риска развития кардиоваскулярных осложнений, напроксен также обладает весьма благоприятным профилем переносимости в отношении почек.…”