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Clinical Review
August 22/29, 2012

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

Author Affiliations
 

Clinical Review Section Editor: Mary McGrae McDermott, MD, Contributing Editor. We encourage authors to submit papers for consideration as a Clinical Review. Please contact Mary McGrae McDermott, MD, at mdm608@northwestern.edu

Author Affiliations: BHF Glasgow Cardiovascular Research Centre (Drs Preiss, Welsh, Sattar, and McMurray) and Robertson Centre for Biostatistics (Dr Ford), University of Glasgow, Glasgow, United Kingdom; University of Helsinki and Division of Cardiology, Helsinki University Hospital, and Folkhalsan Research Center, Helsinki, Finland (Dr Tikkanen); Division of Public Health Sciences, Department of Biostatistical Science, Wake Forest University School of Medicine, Winston-Salem, North Carolina (Ms Lovato); Memphis Veterans Affairs Medical Center, Memphis, Tennessee (Dr Elam); SUNY Health Science Center at Brooklyn, New York, New York (Dr LaRosa); Pfizer Global Pharmaceuticals, New York, New York (Dr DeMicco); Medical Research Institute (Dr Colhoun), Department of Biochemical Medicine (Dr Murphy), and Medicines Monitoring Unit, Division of Medical Sciences (Dr MacDonald), University of Dundee, Dundee, United Kingdom; Cardiac Rehabilitation Institute and Israeli Society for the Prevention of Heart Attacks, Leviev Heart Center, Sheba Medical Center, Tel Hashomer, Israel (Dr Goldenberg); University of Oslo and Centre for Preventative Medicine, Oslo University Hospital, Ulleval, Oslo, Norway (Dr Pedersen); NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia (Dr Keech); Harvard Medical School, Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts (Dr Ridker); and Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway (Dr Kjekshus).

JAMA. 2012;308(8):804-811. doi:10.1001/jama.2012.8439
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.

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