Lipid-modifying therapies and risk of pancreatitis

A meta-analysis

David Preiss, Matti J. Tikkanen, Paul Welsh, Ian Ford, Laura C. Lovato, Marshall Elam, John C. LaRosa, David A. DeMicco, Helen M. Colhoun, Ilan Goldenberg, Michael J. Murphy, Thomas M. MacDonald, Terje R. Pedersen, Anthony C. Keech, Paul M. Ridker, John Kjekshus, Naveed Sattar, John J.V. McMurray

Research output: Contribution to journalReview article

81 Citations (Scopus)

Abstract

Context: Statin therapy has been associated with pancreatitis in observational studies. Although lipid guidelines recommend fibrate therapy to reduce pancreatitis risk in persons with hypertriglyceridemia, fibrates may lead to the development of gallstones, a risk factor for pancreatitis. Objective: To investigate associations between statin or fibrate therapy and incident pancreatitis in large randomized trials. Data Sources: Relevant trials were identified in literature searches of MEDLINE, EMBASE, and Web of Science (January 1, 1994, for statin trials and January 1, 1972, for fibrate trials, through June 9, 2012). Published pancreatitis data were tabulated where available (6 trials). Unpublished data were obtained from investigators (22 trials). Study Selection: We included randomized controlled cardiovascular end-point trials investigating effects of statin therapy or fibrate therapy. Studies with more than 1000 participants followed up for more than 1 year were included. Data Extraction: Trial-specific data described numbers of participants developing pancreatitis and change in triglyceride levels at 1 year. Trial-specific risk ratios (RRs) were calculated and combined using random-effects model meta-analysis. Betweenstudy heterogeneity was assessed using the I2 statistic. Results: In 16 placebo- and standard care-controlled statin trials with 113 800 participants conducted over a weighted mean follow-up of 4.1 (SD, 1.5) years, 309 participants developed pancreatitis (134 assigned to statin, 175 assigned to control) (RR, 0.77 [95% CI, 0.62-0.97; P=.03; I2=0%]). In 5 dose-comparison statin trials with 39 614 participants conducted over 4.8 (SD, 1.7) years, 156 participants developed pancreatitis (70 assigned to intensive dose, 86 assigned to moderate dose) (RR, 0.82 [95% CI, 0.59-1.12; P=.21; I2=0%]). Combined results for all 21 statin trials provided RR 0.79 (95% CI, 0.65-0.95; P=.01; I 2=0%). In 7 fibrate trials with 40 162 participants conducted over 5.3 (SD, 0.5) years, 144 participants developed pancreatitis (84 assigned to fibrate therapy, 60 assigned to placebo) (RR, 1.39 [95% CI, 1.00-1.95; P=.053; I2=0%]). Conclusion: In a pooled analysis of randomized trial data, use of statin therapy was associated with a lower risk of pancreatitis in patients with normal or mildly elevated triglyceride levels.

Original languageEnglish (US)
Pages (from-to)804-811
Number of pages8
JournalJAMA - Journal of the American Medical Association
Volume308
Issue number8
DOIs
StatePublished - Aug 22 2012

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pancreatitis
Fibric Acids
Meta-Analysis
Lipids
Odds Ratio
Therapeutics
Triglycerides
Placebos
Hypertriglyceridemia
Information Storage and Retrieval
Gallstones
MEDLINE
Observational Studies
Research Personnel
Guidelines

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Preiss, D., Tikkanen, M. J., Welsh, P., Ford, I., Lovato, L. C., Elam, M., ... McMurray, J. J. V. (2012). Lipid-modifying therapies and risk of pancreatitis: A meta-analysis. JAMA - Journal of the American Medical Association, 308(8), 804-811. https://doi.org/10.1001/jama.2012.8439

Lipid-modifying therapies and risk of pancreatitis : A meta-analysis. / Preiss, David; Tikkanen, Matti J.; Welsh, Paul; Ford, Ian; Lovato, Laura C.; Elam, Marshall; LaRosa, John C.; DeMicco, David A.; Colhoun, Helen M.; Goldenberg, Ilan; Murphy, Michael J.; MacDonald, Thomas M.; Pedersen, Terje R.; Keech, Anthony C.; Ridker, Paul M.; Kjekshus, John; Sattar, Naveed; McMurray, John J.V.

In: JAMA - Journal of the American Medical Association, Vol. 308, No. 8, 22.08.2012, p. 804-811.

Research output: Contribution to journalReview article

Preiss, D, Tikkanen, MJ, Welsh, P, Ford, I, Lovato, LC, Elam, M, LaRosa, JC, DeMicco, DA, Colhoun, HM, Goldenberg, I, Murphy, MJ, MacDonald, TM, Pedersen, TR, Keech, AC, Ridker, PM, Kjekshus, J, Sattar, N & McMurray, JJV 2012, 'Lipid-modifying therapies and risk of pancreatitis: A meta-analysis', JAMA - Journal of the American Medical Association, vol. 308, no. 8, pp. 804-811. https://doi.org/10.1001/jama.2012.8439
Preiss, David ; Tikkanen, Matti J. ; Welsh, Paul ; Ford, Ian ; Lovato, Laura C. ; Elam, Marshall ; LaRosa, John C. ; DeMicco, David A. ; Colhoun, Helen M. ; Goldenberg, Ilan ; Murphy, Michael J. ; MacDonald, Thomas M. ; Pedersen, Terje R. ; Keech, Anthony C. ; Ridker, Paul M. ; Kjekshus, John ; Sattar, Naveed ; McMurray, John J.V. / Lipid-modifying therapies and risk of pancreatitis : A meta-analysis. In: JAMA - Journal of the American Medical Association. 2012 ; Vol. 308, No. 8. pp. 804-811.
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abstract = "Context: Statin therapy has been associated with pancreatitis in observational studies. Although lipid guidelines recommend fibrate therapy to reduce pancreatitis risk in persons with hypertriglyceridemia, fibrates may lead to the development of gallstones, a risk factor for pancreatitis. Objective: To investigate associations between statin or fibrate therapy and incident pancreatitis in large randomized trials. Data Sources: Relevant trials were identified in literature searches of MEDLINE, EMBASE, and Web of Science (January 1, 1994, for statin trials and January 1, 1972, for fibrate trials, through June 9, 2012). Published pancreatitis data were tabulated where available (6 trials). Unpublished data were obtained from investigators (22 trials). Study Selection: We included randomized controlled cardiovascular end-point trials investigating effects of statin therapy or fibrate therapy. Studies with more than 1000 participants followed up for more than 1 year were included. Data Extraction: Trial-specific data described numbers of participants developing pancreatitis and change in triglyceride levels at 1 year. Trial-specific risk ratios (RRs) were calculated and combined using random-effects model meta-analysis. Betweenstudy heterogeneity was assessed using the I2 statistic. Results: In 16 placebo- and standard care-controlled statin trials with 113 800 participants conducted over a weighted mean follow-up of 4.1 (SD, 1.5) years, 309 participants developed pancreatitis (134 assigned to statin, 175 assigned to control) (RR, 0.77 [95{\%} CI, 0.62-0.97; P=.03; I2=0{\%}]). In 5 dose-comparison statin trials with 39 614 participants conducted over 4.8 (SD, 1.7) years, 156 participants developed pancreatitis (70 assigned to intensive dose, 86 assigned to moderate dose) (RR, 0.82 [95{\%} CI, 0.59-1.12; P=.21; I2=0{\%}]). Combined results for all 21 statin trials provided RR 0.79 (95{\%} CI, 0.65-0.95; P=.01; I 2=0{\%}). In 7 fibrate trials with 40 162 participants conducted over 5.3 (SD, 0.5) years, 144 participants developed pancreatitis (84 assigned to fibrate therapy, 60 assigned to placebo) (RR, 1.39 [95{\%} CI, 1.00-1.95; P=.053; I2=0{\%}]). Conclusion: In a pooled analysis of randomized trial data, use of statin therapy was associated with a lower risk of pancreatitis in patients with normal or mildly elevated triglyceride levels.",
author = "David Preiss and Tikkanen, {Matti J.} and Paul Welsh and Ian Ford and Lovato, {Laura C.} and Marshall Elam and LaRosa, {John C.} and DeMicco, {David A.} and Colhoun, {Helen M.} and Ilan Goldenberg and Murphy, {Michael J.} and MacDonald, {Thomas M.} and Pedersen, {Terje R.} and Keech, {Anthony C.} and Ridker, {Paul M.} and John Kjekshus and Naveed Sattar and McMurray, {John J.V.}",
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T1 - Lipid-modifying therapies and risk of pancreatitis

T2 - A meta-analysis

AU - Preiss, David

AU - Tikkanen, Matti J.

AU - Welsh, Paul

AU - Ford, Ian

AU - Lovato, Laura C.

AU - Elam, Marshall

AU - LaRosa, John C.

AU - DeMicco, David A.

AU - Colhoun, Helen M.

AU - Goldenberg, Ilan

AU - Murphy, Michael J.

AU - MacDonald, Thomas M.

AU - Pedersen, Terje R.

AU - Keech, Anthony C.

AU - Ridker, Paul M.

AU - Kjekshus, John

AU - Sattar, Naveed

AU - McMurray, John J.V.

PY - 2012/8/22

Y1 - 2012/8/22

N2 - Context: Statin therapy has been associated with pancreatitis in observational studies. Although lipid guidelines recommend fibrate therapy to reduce pancreatitis risk in persons with hypertriglyceridemia, fibrates may lead to the development of gallstones, a risk factor for pancreatitis. Objective: To investigate associations between statin or fibrate therapy and incident pancreatitis in large randomized trials. Data Sources: Relevant trials were identified in literature searches of MEDLINE, EMBASE, and Web of Science (January 1, 1994, for statin trials and January 1, 1972, for fibrate trials, through June 9, 2012). Published pancreatitis data were tabulated where available (6 trials). Unpublished data were obtained from investigators (22 trials). Study Selection: We included randomized controlled cardiovascular end-point trials investigating effects of statin therapy or fibrate therapy. Studies with more than 1000 participants followed up for more than 1 year were included. Data Extraction: Trial-specific data described numbers of participants developing pancreatitis and change in triglyceride levels at 1 year. Trial-specific risk ratios (RRs) were calculated and combined using random-effects model meta-analysis. Betweenstudy heterogeneity was assessed using the I2 statistic. Results: In 16 placebo- and standard care-controlled statin trials with 113 800 participants conducted over a weighted mean follow-up of 4.1 (SD, 1.5) years, 309 participants developed pancreatitis (134 assigned to statin, 175 assigned to control) (RR, 0.77 [95% CI, 0.62-0.97; P=.03; I2=0%]). In 5 dose-comparison statin trials with 39 614 participants conducted over 4.8 (SD, 1.7) years, 156 participants developed pancreatitis (70 assigned to intensive dose, 86 assigned to moderate dose) (RR, 0.82 [95% CI, 0.59-1.12; P=.21; I2=0%]). Combined results for all 21 statin trials provided RR 0.79 (95% CI, 0.65-0.95; P=.01; I 2=0%). In 7 fibrate trials with 40 162 participants conducted over 5.3 (SD, 0.5) years, 144 participants developed pancreatitis (84 assigned to fibrate therapy, 60 assigned to placebo) (RR, 1.39 [95% CI, 1.00-1.95; P=.053; I2=0%]). Conclusion: In a pooled analysis of randomized trial data, use of statin therapy was associated with a lower risk of pancreatitis in patients with normal or mildly elevated triglyceride levels.

AB - Context: Statin therapy has been associated with pancreatitis in observational studies. Although lipid guidelines recommend fibrate therapy to reduce pancreatitis risk in persons with hypertriglyceridemia, fibrates may lead to the development of gallstones, a risk factor for pancreatitis. Objective: To investigate associations between statin or fibrate therapy and incident pancreatitis in large randomized trials. Data Sources: Relevant trials were identified in literature searches of MEDLINE, EMBASE, and Web of Science (January 1, 1994, for statin trials and January 1, 1972, for fibrate trials, through June 9, 2012). Published pancreatitis data were tabulated where available (6 trials). Unpublished data were obtained from investigators (22 trials). Study Selection: We included randomized controlled cardiovascular end-point trials investigating effects of statin therapy or fibrate therapy. Studies with more than 1000 participants followed up for more than 1 year were included. Data Extraction: Trial-specific data described numbers of participants developing pancreatitis and change in triglyceride levels at 1 year. Trial-specific risk ratios (RRs) were calculated and combined using random-effects model meta-analysis. Betweenstudy heterogeneity was assessed using the I2 statistic. Results: In 16 placebo- and standard care-controlled statin trials with 113 800 participants conducted over a weighted mean follow-up of 4.1 (SD, 1.5) years, 309 participants developed pancreatitis (134 assigned to statin, 175 assigned to control) (RR, 0.77 [95% CI, 0.62-0.97; P=.03; I2=0%]). In 5 dose-comparison statin trials with 39 614 participants conducted over 4.8 (SD, 1.7) years, 156 participants developed pancreatitis (70 assigned to intensive dose, 86 assigned to moderate dose) (RR, 0.82 [95% CI, 0.59-1.12; P=.21; I2=0%]). Combined results for all 21 statin trials provided RR 0.79 (95% CI, 0.65-0.95; P=.01; I 2=0%). In 7 fibrate trials with 40 162 participants conducted over 5.3 (SD, 0.5) years, 144 participants developed pancreatitis (84 assigned to fibrate therapy, 60 assigned to placebo) (RR, 1.39 [95% CI, 1.00-1.95; P=.053; I2=0%]). Conclusion: In a pooled analysis of randomized trial data, use of statin therapy was associated with a lower risk of pancreatitis in patients with normal or mildly elevated triglyceride levels.

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