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

Study Questions:

What are the associations between use of a statin or a fibrate and the incidence of pancreatitis among patients with normal or mildly elevated triglyceride levels?

Methods:

This was a meta-analysis of published and unpublished data from large randomized cardiovascular endpoint trials designed to assess the effects of statin or fibrate therapy. Trials with more than 1,000 participants followed up to 1 year were included. By tabulating published pancreatitis data and obtaining unpublished data from investigators, the number of participants who developed pancreatitis was determined. Trial-specific change in triglyceride levels at 1 year was included in the analysis. Trial-specific risk ratios were calculated and combined using random-effects model meta-analysis.

Results:

Twenty-one statin trials were included in the analysis. Among 153,414 participants from these 21 trials, 465 (0.30%) developed pancreatitis (of whom 204 were assigned to statin therapy or intensive-dose statin, and 261 were assigned to placebo, standard care, or moderate-dose statin), yielding a risk ratio (RR) of 0.79 (95% confidence interval [CI], 0.65-0.95; p = 0.01). Seven fibrate trials were included in the analysis. Among 40,162 participants from these seven trials, 144 (0.36%) developed pancreatitis (84 assigned to fibrate therapy, 60 assigned to placebo), yielding a RR of 1.39 (95% CI, 1.00-1.95; p = 0.053). In all 28 trials, baseline triglyceride levels were normal to mildly elevated (118-187 mg/dl in the statin trials and 145-184 mg/dl in the fibrate trials).

Conclusions:

Pooled data from randomized trials where pancreatitis was not a prespecified endpoint suggests that statin therapy, and not fibrate therapy, may be associated with a lower risk of developing pancreatitis.

Perspective:

This meta-analysis suggests that statin therapy may be associated with a reduced risk of pancreatitis and may be the preferred lipid-modifying agent (versus fibrates) for preventing pancreatitis in those with only slightly elevated triglycerides levels. Although the present study was based on data from randomized trials, a major limitation is the very small number of pancreatitis cases (0.30% and 0.36% of participants in the statin and fibrate trials, respectively), limiting application of the study findings.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins

Keywords: Incidence, Fibric Acids, Risk, Pancreatitis, Lipid Metabolism, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypertriglyceridemia, Body Weight, Cardiovascular Diseases, Triglycerides


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