Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: Meta-analyses of individual participant data from randomised trials

Colin Baigent, N. Bhala, J. Emberson, A. Merhi, S. Abramson, N. Arber, J. A. Baron, C. Bombardier, C. Cannon, M. E. Farkouh, G. A. FitzGerald, P. Goss, H. Halls, E. Hawk, C. Hawkey, C. Hennekens, M. Hochberg, L. E. Holland, P. M. Kearney, L. LaineA. Lanas, P. Lance, A. Laupacis, J. Oates, C. Patrono, T. J. Schnitzer, S. Solomon, P. Tugwell, K. Wilson, J. Wittes, O. Adelowo, P. Aisen, A. Al-Quorain, Roy D Altman, G. Bakris, H. Baumgartner, C. Bresee, M. Carducci, D. M. Chang, C. T. Chou, D. Clegg, M. Cudkowicz, L. Doody, Y. El Miedany, C. Falandry, J. Farley, L. Ford, M. Garcia-Losa, M. Gonzalez-Ortiz, M. Haghighi, M. Hala, T. Iwama, Z. Jajic, D. Kerr, H. S. Kim, C. Kohne, B. K. Koo, B. Martin, C. Meinert, N. Muller, G. Myklebust, D. Neustadt, R. Omdal, S. Ozgocmen, A. Papas, P. Patrignani, F. Pelliccia, V. Roy, I. Schlegelmilch, A. Umar, O. Wahlstrom, F. Wollheim, S. Yocum, X. Y. Zhang, E. Hall, P. McGettigan, R. Midgley, R. A. Moore, R. Philipson, S. Curtis, A. Reicin, J. Bond, A. Moore, M. Essex, J. Fabule, B. Morrison, L. Tive, N. Bhala, K. Davies, J. Emberson, H. Halls, L. E. Holland, P. M. Kearney, A. Merhi, C. Patrono, K. Wilson, F. Yau

Research output: Contribution to journalArticle

811 Citations (Scopus)

Abstract

Background The vascular and gastrointestinal effects of non-steroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors (coxibs) and traditional non-steroidal anti-inflammatory drugs (tNSAIDs), are not well characterised, particularly in patients at increased risk of vascular disease. We aimed to provide such information through meta-analyses of randomised trials. Methods We undertook meta-analyses of 280 trials of NSAIDs versus placebo (124 513 participants, 68 342 personyears) and 474 trials of one NSAID versus another NSAID (229 296 participants, 165 456 person-years). The main outcomes were major vascular events (non-fatal myocardial in farction, non-fatal stroke, or vascular death); major coronary events (non-fatal myocardial infarction or coronary death); stroke; mortality; heart failure; and upper gastrointestinal complications (perforation, ob struction, or bleed). Findings Major vascular events were increased by about a third by a coxib (rate ratio [RR] 1·37, 95% CI 1·14-1·66; p=0·0009) or diclofenac (1·41, 1·12-1·78; p=0·0036), chiefl y due to an increase in major coronary events (coxibs 1·76, 1·31-2·37; p=0·0001; diclofenac 1·70, 1·19-2·41; p=0·0032). Ibuprofen also significantly increased major coronary events (2·22, 1·10-4·48; p=0·0253), but not major vascular events (1·44, 0·89-2·33). Compared with placebo, of 1000 patients allocated to a coxib or diclofenac for a year, three more had major vascular events, one of which was fatal. Naproxen did not significantly increase major vascular events (0·93, 0·69-1·27). Vascular death was increased significantly by coxibs (1·58, 99% CI 1·00-2·49; p=0·0103) and diclofenac (1·65, 0·95-2·85, p=0·0187), nonsignificantly by ibuprofen (1·90, 0·56-6·41; p=0·17), but not by naproxen (1·08, 0·48-2·47, p=0·80). The proportional eff ects on major vascular events were independent of baseline characteristics, including vascular risk. Heart failure risk was roughly doubled by all NSAIDs. All NSAID regimens increased upper gastrointestinal complications (coxibs 1·81, 1·17-2·81, p=0·0070; diclofenac 1·89, 1·16-3·09, p=0·0106; ibuprofen 3·97, 2·22-7·10, p

Original languageEnglish (US)
Pages (from-to)769-779
Number of pages11
JournalThe Lancet
Volume382
Issue number9894
DOIs
StatePublished - 2013
Externally publishedYes

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Blood Vessels
Meta-Analysis
Anti-Inflammatory Agents
Diclofenac
Pharmaceutical Preparations
Cyclooxygenase 2 Inhibitors
Ibuprofen
Naproxen
Heart Failure
Stroke
Placebos
Vascular Diseases
Myocardial Infarction
Mortality

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs : Meta-analyses of individual participant data from randomised trials. / Baigent, Colin; Bhala, N.; Emberson, J.; Merhi, A.; Abramson, S.; Arber, N.; Baron, J. A.; Bombardier, C.; Cannon, C.; Farkouh, M. E.; FitzGerald, G. A.; Goss, P.; Halls, H.; Hawk, E.; Hawkey, C.; Hennekens, C.; Hochberg, M.; Holland, L. E.; Kearney, P. M.; Laine, L.; Lanas, A.; Lance, P.; Laupacis, A.; Oates, J.; Patrono, C.; Schnitzer, T. J.; Solomon, S.; Tugwell, P.; Wilson, K.; Wittes, J.; Adelowo, O.; Aisen, P.; Al-Quorain, A.; Altman, Roy D; Bakris, G.; Baumgartner, H.; Bresee, C.; Carducci, M.; Chang, D. M.; Chou, C. T.; Clegg, D.; Cudkowicz, M.; Doody, L.; Miedany, Y. El; Falandry, C.; Farley, J.; Ford, L.; Garcia-Losa, M.; Gonzalez-Ortiz, M.; Haghighi, M.; Hala, M.; Iwama, T.; Jajic, Z.; Kerr, D.; Kim, H. S.; Kohne, C.; Koo, B. K.; Martin, B.; Meinert, C.; Muller, N.; Myklebust, G.; Neustadt, D.; Omdal, R.; Ozgocmen, S.; Papas, A.; Patrignani, P.; Pelliccia, F.; Roy, V.; Schlegelmilch, I.; Umar, A.; Wahlstrom, O.; Wollheim, F.; Yocum, S.; Zhang, X. Y.; Hall, E.; McGettigan, P.; Midgley, R.; Moore, R. A.; Philipson, R.; Curtis, S.; Reicin, A.; Bond, J.; Moore, A.; Essex, M.; Fabule, J.; Morrison, B.; Tive, L.; Bhala, N.; Davies, K.; Emberson, J.; Halls, H.; Holland, L. E.; Kearney, P. M.; Merhi, A.; Patrono, C.; Wilson, K.; Yau, F.

In: The Lancet, Vol. 382, No. 9894, 2013, p. 769-779.

Research output: Contribution to journalArticle

Baigent, C, Bhala, N, Emberson, J, Merhi, A, Abramson, S, Arber, N, Baron, JA, Bombardier, C, Cannon, C, Farkouh, ME, FitzGerald, GA, Goss, P, Halls, H, Hawk, E, Hawkey, C, Hennekens, C, Hochberg, M, Holland, LE, Kearney, PM, Laine, L, Lanas, A, Lance, P, Laupacis, A, Oates, J, Patrono, C, Schnitzer, TJ, Solomon, S, Tugwell, P, Wilson, K, Wittes, J, Adelowo, O, Aisen, P, Al-Quorain, A, Altman, RD, Bakris, G, Baumgartner, H, Bresee, C, Carducci, M, Chang, DM, Chou, CT, Clegg, D, Cudkowicz, M, Doody, L, Miedany, YE, Falandry, C, Farley, J, Ford, L, Garcia-Losa, M, Gonzalez-Ortiz, M, Haghighi, M, Hala, M, Iwama, T, Jajic, Z, Kerr, D, Kim, HS, Kohne, C, Koo, BK, Martin, B, Meinert, C, Muller, N, Myklebust, G, Neustadt, D, Omdal, R, Ozgocmen, S, Papas, A, Patrignani, P, Pelliccia, F, Roy, V, Schlegelmilch, I, Umar, A, Wahlstrom, O, Wollheim, F, Yocum, S, Zhang, XY, Hall, E, McGettigan, P, Midgley, R, Moore, RA, Philipson, R, Curtis, S, Reicin, A, Bond, J, Moore, A, Essex, M, Fabule, J, Morrison, B, Tive, L, Bhala, N, Davies, K, Emberson, J, Halls, H, Holland, LE, Kearney, PM, Merhi, A, Patrono, C, Wilson, K & Yau, F 2013, 'Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: Meta-analyses of individual participant data from randomised trials', The Lancet, vol. 382, no. 9894, pp. 769-779. https://doi.org/10.1016/S0140-6736(13)60900-9
Baigent, Colin ; Bhala, N. ; Emberson, J. ; Merhi, A. ; Abramson, S. ; Arber, N. ; Baron, J. A. ; Bombardier, C. ; Cannon, C. ; Farkouh, M. E. ; FitzGerald, G. A. ; Goss, P. ; Halls, H. ; Hawk, E. ; Hawkey, C. ; Hennekens, C. ; Hochberg, M. ; Holland, L. E. ; Kearney, P. M. ; Laine, L. ; Lanas, A. ; Lance, P. ; Laupacis, A. ; Oates, J. ; Patrono, C. ; Schnitzer, T. J. ; Solomon, S. ; Tugwell, P. ; Wilson, K. ; Wittes, J. ; Adelowo, O. ; Aisen, P. ; Al-Quorain, A. ; Altman, Roy D ; Bakris, G. ; Baumgartner, H. ; Bresee, C. ; Carducci, M. ; Chang, D. M. ; Chou, C. T. ; Clegg, D. ; Cudkowicz, M. ; Doody, L. ; Miedany, Y. El ; Falandry, C. ; Farley, J. ; Ford, L. ; Garcia-Losa, M. ; Gonzalez-Ortiz, M. ; Haghighi, M. ; Hala, M. ; Iwama, T. ; Jajic, Z. ; Kerr, D. ; Kim, H. S. ; Kohne, C. ; Koo, B. K. ; Martin, B. ; Meinert, C. ; Muller, N. ; Myklebust, G. ; Neustadt, D. ; Omdal, R. ; Ozgocmen, S. ; Papas, A. ; Patrignani, P. ; Pelliccia, F. ; Roy, V. ; Schlegelmilch, I. ; Umar, A. ; Wahlstrom, O. ; Wollheim, F. ; Yocum, S. ; Zhang, X. Y. ; Hall, E. ; McGettigan, P. ; Midgley, R. ; Moore, R. A. ; Philipson, R. ; Curtis, S. ; Reicin, A. ; Bond, J. ; Moore, A. ; Essex, M. ; Fabule, J. ; Morrison, B. ; Tive, L. ; Bhala, N. ; Davies, K. ; Emberson, J. ; Halls, H. ; Holland, L. E. ; Kearney, P. M. ; Merhi, A. ; Patrono, C. ; Wilson, K. ; Yau, F. / Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs : Meta-analyses of individual participant data from randomised trials. In: The Lancet. 2013 ; Vol. 382, No. 9894. pp. 769-779.
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abstract = "Background The vascular and gastrointestinal effects of non-steroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors (coxibs) and traditional non-steroidal anti-inflammatory drugs (tNSAIDs), are not well characterised, particularly in patients at increased risk of vascular disease. We aimed to provide such information through meta-analyses of randomised trials. Methods We undertook meta-analyses of 280 trials of NSAIDs versus placebo (124 513 participants, 68 342 personyears) and 474 trials of one NSAID versus another NSAID (229 296 participants, 165 456 person-years). The main outcomes were major vascular events (non-fatal myocardial in farction, non-fatal stroke, or vascular death); major coronary events (non-fatal myocardial infarction or coronary death); stroke; mortality; heart failure; and upper gastrointestinal complications (perforation, ob struction, or bleed). Findings Major vascular events were increased by about a third by a coxib (rate ratio [RR] 1·37, 95{\%} CI 1·14-1·66; p=0·0009) or diclofenac (1·41, 1·12-1·78; p=0·0036), chiefl y due to an increase in major coronary events (coxibs 1·76, 1·31-2·37; p=0·0001; diclofenac 1·70, 1·19-2·41; p=0·0032). Ibuprofen also significantly increased major coronary events (2·22, 1·10-4·48; p=0·0253), but not major vascular events (1·44, 0·89-2·33). Compared with placebo, of 1000 patients allocated to a coxib or diclofenac for a year, three more had major vascular events, one of which was fatal. Naproxen did not significantly increase major vascular events (0·93, 0·69-1·27). Vascular death was increased significantly by coxibs (1·58, 99{\%} CI 1·00-2·49; p=0·0103) and diclofenac (1·65, 0·95-2·85, p=0·0187), nonsignificantly by ibuprofen (1·90, 0·56-6·41; p=0·17), but not by naproxen (1·08, 0·48-2·47, p=0·80). The proportional eff ects on major vascular events were independent of baseline characteristics, including vascular risk. Heart failure risk was roughly doubled by all NSAIDs. All NSAID regimens increased upper gastrointestinal complications (coxibs 1·81, 1·17-2·81, p=0·0070; diclofenac 1·89, 1·16-3·09, p=0·0106; ibuprofen 3·97, 2·22-7·10, p",
author = "Colin Baigent and N. Bhala and J. Emberson and A. Merhi and S. Abramson and N. Arber and Baron, {J. A.} and C. Bombardier and C. Cannon and Farkouh, {M. E.} and FitzGerald, {G. A.} and P. Goss and H. Halls and E. Hawk and C. Hawkey and C. Hennekens and M. Hochberg and Holland, {L. E.} and Kearney, {P. M.} and L. Laine and A. Lanas and P. Lance and A. Laupacis and J. Oates and C. Patrono and Schnitzer, {T. J.} and S. Solomon and P. Tugwell and K. Wilson and J. Wittes and O. Adelowo and P. Aisen and A. Al-Quorain and Altman, {Roy D} and G. Bakris and H. Baumgartner and C. Bresee and M. Carducci and Chang, {D. M.} and Chou, {C. T.} and D. Clegg and M. Cudkowicz and L. Doody and Miedany, {Y. El} and C. Falandry and J. Farley and L. Ford and M. Garcia-Losa and M. Gonzalez-Ortiz and M. Haghighi and M. Hala and T. Iwama and Z. Jajic and D. Kerr and Kim, {H. S.} and C. Kohne and Koo, {B. K.} and B. Martin and C. Meinert and N. Muller and G. Myklebust and D. Neustadt and R. Omdal and S. Ozgocmen and A. Papas and P. Patrignani and F. Pelliccia and V. Roy and I. Schlegelmilch and A. Umar and O. Wahlstrom and F. Wollheim and S. Yocum and Zhang, {X. Y.} and E. Hall and P. McGettigan and R. Midgley and Moore, {R. A.} and R. Philipson and S. Curtis and A. Reicin and J. Bond and A. Moore and M. Essex and J. Fabule and B. Morrison and L. Tive and N. Bhala and K. Davies and J. Emberson and H. Halls and Holland, {L. E.} and Kearney, {P. M.} and A. Merhi and C. Patrono and K. Wilson and F. Yau",
year = "2013",
doi = "10.1016/S0140-6736(13)60900-9",
language = "English (US)",
volume = "382",
pages = "769--779",
journal = "The Lancet",
issn = "0140-6736",
publisher = "Elsevier Limited",
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TY - JOUR

T1 - Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs

T2 - Meta-analyses of individual participant data from randomised trials

AU - Baigent, Colin

AU - Bhala, N.

AU - Emberson, J.

AU - Merhi, A.

AU - Abramson, S.

AU - Arber, N.

AU - Baron, J. A.

AU - Bombardier, C.

AU - Cannon, C.

AU - Farkouh, M. E.

AU - FitzGerald, G. A.

AU - Goss, P.

AU - Halls, H.

AU - Hawk, E.

AU - Hawkey, C.

AU - Hennekens, C.

AU - Hochberg, M.

AU - Holland, L. E.

AU - Kearney, P. M.

AU - Laine, L.

AU - Lanas, A.

AU - Lance, P.

AU - Laupacis, A.

AU - Oates, J.

AU - Patrono, C.

AU - Schnitzer, T. J.

AU - Solomon, S.

AU - Tugwell, P.

AU - Wilson, K.

AU - Wittes, J.

AU - Adelowo, O.

AU - Aisen, P.

AU - Al-Quorain, A.

AU - Altman, Roy D

AU - Bakris, G.

AU - Baumgartner, H.

AU - Bresee, C.

AU - Carducci, M.

AU - Chang, D. M.

AU - Chou, C. T.

AU - Clegg, D.

AU - Cudkowicz, M.

AU - Doody, L.

AU - Miedany, Y. El

AU - Falandry, C.

AU - Farley, J.

AU - Ford, L.

AU - Garcia-Losa, M.

AU - Gonzalez-Ortiz, M.

AU - Haghighi, M.

AU - Hala, M.

AU - Iwama, T.

AU - Jajic, Z.

AU - Kerr, D.

AU - Kim, H. S.

AU - Kohne, C.

AU - Koo, B. K.

AU - Martin, B.

AU - Meinert, C.

AU - Muller, N.

AU - Myklebust, G.

AU - Neustadt, D.

AU - Omdal, R.

AU - Ozgocmen, S.

AU - Papas, A.

AU - Patrignani, P.

AU - Pelliccia, F.

AU - Roy, V.

AU - Schlegelmilch, I.

AU - Umar, A.

AU - Wahlstrom, O.

AU - Wollheim, F.

AU - Yocum, S.

AU - Zhang, X. Y.

AU - Hall, E.

AU - McGettigan, P.

AU - Midgley, R.

AU - Moore, R. A.

AU - Philipson, R.

AU - Curtis, S.

AU - Reicin, A.

AU - Bond, J.

AU - Moore, A.

AU - Essex, M.

AU - Fabule, J.

AU - Morrison, B.

AU - Tive, L.

AU - Bhala, N.

AU - Davies, K.

AU - Emberson, J.

AU - Halls, H.

AU - Holland, L. E.

AU - Kearney, P. M.

AU - Merhi, A.

AU - Patrono, C.

AU - Wilson, K.

AU - Yau, F.

PY - 2013

Y1 - 2013

N2 - Background The vascular and gastrointestinal effects of non-steroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors (coxibs) and traditional non-steroidal anti-inflammatory drugs (tNSAIDs), are not well characterised, particularly in patients at increased risk of vascular disease. We aimed to provide such information through meta-analyses of randomised trials. Methods We undertook meta-analyses of 280 trials of NSAIDs versus placebo (124 513 participants, 68 342 personyears) and 474 trials of one NSAID versus another NSAID (229 296 participants, 165 456 person-years). The main outcomes were major vascular events (non-fatal myocardial in farction, non-fatal stroke, or vascular death); major coronary events (non-fatal myocardial infarction or coronary death); stroke; mortality; heart failure; and upper gastrointestinal complications (perforation, ob struction, or bleed). Findings Major vascular events were increased by about a third by a coxib (rate ratio [RR] 1·37, 95% CI 1·14-1·66; p=0·0009) or diclofenac (1·41, 1·12-1·78; p=0·0036), chiefl y due to an increase in major coronary events (coxibs 1·76, 1·31-2·37; p=0·0001; diclofenac 1·70, 1·19-2·41; p=0·0032). Ibuprofen also significantly increased major coronary events (2·22, 1·10-4·48; p=0·0253), but not major vascular events (1·44, 0·89-2·33). Compared with placebo, of 1000 patients allocated to a coxib or diclofenac for a year, three more had major vascular events, one of which was fatal. Naproxen did not significantly increase major vascular events (0·93, 0·69-1·27). Vascular death was increased significantly by coxibs (1·58, 99% CI 1·00-2·49; p=0·0103) and diclofenac (1·65, 0·95-2·85, p=0·0187), nonsignificantly by ibuprofen (1·90, 0·56-6·41; p=0·17), but not by naproxen (1·08, 0·48-2·47, p=0·80). The proportional eff ects on major vascular events were independent of baseline characteristics, including vascular risk. Heart failure risk was roughly doubled by all NSAIDs. All NSAID regimens increased upper gastrointestinal complications (coxibs 1·81, 1·17-2·81, p=0·0070; diclofenac 1·89, 1·16-3·09, p=0·0106; ibuprofen 3·97, 2·22-7·10, p

AB - Background The vascular and gastrointestinal effects of non-steroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors (coxibs) and traditional non-steroidal anti-inflammatory drugs (tNSAIDs), are not well characterised, particularly in patients at increased risk of vascular disease. We aimed to provide such information through meta-analyses of randomised trials. Methods We undertook meta-analyses of 280 trials of NSAIDs versus placebo (124 513 participants, 68 342 personyears) and 474 trials of one NSAID versus another NSAID (229 296 participants, 165 456 person-years). The main outcomes were major vascular events (non-fatal myocardial in farction, non-fatal stroke, or vascular death); major coronary events (non-fatal myocardial infarction or coronary death); stroke; mortality; heart failure; and upper gastrointestinal complications (perforation, ob struction, or bleed). Findings Major vascular events were increased by about a third by a coxib (rate ratio [RR] 1·37, 95% CI 1·14-1·66; p=0·0009) or diclofenac (1·41, 1·12-1·78; p=0·0036), chiefl y due to an increase in major coronary events (coxibs 1·76, 1·31-2·37; p=0·0001; diclofenac 1·70, 1·19-2·41; p=0·0032). Ibuprofen also significantly increased major coronary events (2·22, 1·10-4·48; p=0·0253), but not major vascular events (1·44, 0·89-2·33). Compared with placebo, of 1000 patients allocated to a coxib or diclofenac for a year, three more had major vascular events, one of which was fatal. Naproxen did not significantly increase major vascular events (0·93, 0·69-1·27). Vascular death was increased significantly by coxibs (1·58, 99% CI 1·00-2·49; p=0·0103) and diclofenac (1·65, 0·95-2·85, p=0·0187), nonsignificantly by ibuprofen (1·90, 0·56-6·41; p=0·17), but not by naproxen (1·08, 0·48-2·47, p=0·80). The proportional eff ects on major vascular events were independent of baseline characteristics, including vascular risk. Heart failure risk was roughly doubled by all NSAIDs. All NSAID regimens increased upper gastrointestinal complications (coxibs 1·81, 1·17-2·81, p=0·0070; diclofenac 1·89, 1·16-3·09, p=0·0106; ibuprofen 3·97, 2·22-7·10, p

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U2 - 10.1016/S0140-6736(13)60900-9

DO - 10.1016/S0140-6736(13)60900-9

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AN - SCOPUS:84883134602

VL - 382

SP - 769

EP - 779

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 9894

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