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

Carlo Alberto Barcella; Morten Lamberts; Patricia McGettigan; Emil Loldrup Fosbøl; Jesper Lindhardsen; Christian Torp-Pedersen; Gunnar Hilmar Gislason; Anne-Marie Schjerning Olsen

doi:10.1111/bcpt.13182

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

Carlo Alberto Barcella, Morten Lamberts, Patricia McGettigan, Emil Loldrup Fosbøl, Jesper Lindhardsen, Christian Torp-Pedersen, Gunnar Hilmar Gislason, Anne-Marie Schjerning Olsen

Institut for Klinisk Medicin

10 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Basic & Clinical Pharmacology & Toxicology
Vol/bind	124
Udgave nummer	5
Sider (fra-til)	629-641
Antal sider	13
ISSN	1742-7835
DOI	https://doi.org/10.1111/bcpt.13182
Status	Udgivet - maj 2019

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10.1111/bcpt.13182

bcpt.13182Forlagets udgivne version, 784 KB

Citationsformater

Barcella, C. A., Lamberts, M., McGettigan, P., Fosbøl, E. L., Lindhardsen, J., Torp-Pedersen, C., Gislason, G. H., & Olsen, A-M. S. (2019). Differences in cardiovascular safety with non-steroidal anti-inflammatory drug therapy - A nationwide study in patients with osteoarthritis. Basic & Clinical Pharmacology & Toxicology, 124(5), 629-641. https://doi.org/10.1111/bcpt.13182

Differences in cardiovascular safety with non-steroidal anti-inflammatory drug therapy - A nationwide study in patients with osteoarthritis. / Barcella, Carlo Alberto; Lamberts, Morten; McGettigan, Patricia et al.

I: Basic & Clinical Pharmacology & Toxicology, Bind 124, Nr. 5, 05.2019, s. 629-641.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Barcella, CA, Lamberts, M, McGettigan, P, Fosbøl, EL, Lindhardsen, J, Torp-Pedersen, C, Gislason, GH & Olsen, A-MS 2019, 'Differences in cardiovascular safety with non-steroidal anti-inflammatory drug therapy - A nationwide study in patients with osteoarthritis', Basic & Clinical Pharmacology & Toxicology, bind 124, nr. 5, s. 629-641. https://doi.org/10.1111/bcpt.13182

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title = "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.",

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AU - Barcella, Carlo Alberto

AU - Lamberts, Morten

AU - McGettigan, Patricia

AU - Fosbøl, Emil Loldrup

AU - Lindhardsen, Jesper

AU - Torp-Pedersen, Christian

AU - Gislason, Gunnar Hilmar

AU - Olsen, Anne-Marie Schjerning

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N2 - 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.

AB - 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.

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DO - 10.1111/bcpt.13182

M3 - Journal article

C2 - 30484960

SN - 1742-7835

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JO - Basic and Clinical Pharmacology and Toxicology

JF - Basic and Clinical Pharmacology and Toxicology

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ER -

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

Abstract

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