Lipid-Modifying Therapies and Risk of Pancreatitis: A Meta-analysis

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 T...

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Bibliographic Details
Published in:JAMA : the journal of the American Medical Association 2012-08, Vol.308 (8), p.804-811
Main Authors: Preiss, David, Tikkanen, Matti J, Welsh, Paul, Ford, Ian, Lovato, Laura C, Elam, Marshall B, 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
Format: Article
Language:English
Subjects:
Biological and medical sciences
Clinical trials
Fibric Acids - adverse effects
Fibric Acids - therapeutic use
Gallstones
Gallstones - chemically induced
Gallstones - complications
Gastroenterology. Liver. Pancreas. Abdomen
General aspects
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects
Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use
Hyperlipidemias - drug therapy
Hypertriglyceridemia - complications
Hypertriglyceridemia - drug therapy
Incidence
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Medical sciences
Meta-analysis
Other diseases. Semiology
Pancreas
Pancreatitis - chemically induced
Pancreatitis - epidemiology
Pancreatitis - prevention & control
Randomized Controlled Trials as Topic
Risk
Statins
Systematic review
Triglycerides
Triglycerides - blood
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Summary: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 Unpublished data were obtained from investigators (22 trials).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. Between-study 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; I2 = 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.
ISSN:0098-7484
1538-3598
DOI:10.1001/jama.2012.8439