Lipid-modifying therapies and risk of pancreatitis: a meta-analysis

Preiss, D. et al. (2012) Lipid-modifying therapies and risk of pancreatitis: a meta-analysis. JAMA: Journal of the American Medical Association, 308(8), pp. 804-811. (doi:10.1001/jama.2012.8439)

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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 Unpublished data were obtained from investigators (22 trials).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. 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Welsh, Dr Paul and McMurray, Professor John and Ford, Professor Ian and Preiss, Dr David and Sattar, Professor Naveed
Authors: Preiss, D., Tikkanen, M. J., Welsh, P., Ford, I., Lovato, L. C., Elam, M. B., LaRosa, J. C., DeMicco, D. A., Colhoun, H. M., Goldenberg, I., Murphy, M. J., MacDonald, T. M., Pedersen, T. R., Keech, A. C., Ridker, P. M., Kjekshus, J., Sattar, N., and McMurray, J. J. V.
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:JAMA: Journal of the American Medical Association
Publisher:American Medical Association
ISSN:0098-7484
ISSN (Online):1538-3598
Copyright Holders:Copyright © 2012 The Authors
First Published:First published in JAMA: Journal of the American Medical Association 308(8):804-811
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
531741NT-proBNP as a predictor of vascular events in WOSCOPS: using modern epidemiological techniques to test clinical utility of a biomarkerPaul WelshBritish Heart Foundation (BHF)FS/10/005/28147RI CARDIOVASCULAR & MEDICAL SCIENCES