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.