Statins May Lower Risk for Pancreatitis

 Despite opposing results from early observational studies, a new meta-analysis suggests that statins may reduce the risk of developing pancreatitis among patients with normal to slightly elevated triglyceride levels. Findings from the study, conducted by David Preiss, MD, PhD, from BHF Glasgow Cardiovascular Research Centre in the United Kingdom, and colleagues, were published in the August 22/29 issue of JAMA.

Patients with pancreatitis can experience a range of outcomes, from mild, self-limiting episodes to severe or fatal events. Hypertriglyceridemia is the third most common cause of pancreatitis, but the medicines prescribed to lower triglyceride levels carry their own worries. Studies have linked pancreatitis to use of statins, which, as a class, represented $20.1 billion in US sales last year, according to IMS Health, a healthcare information company.
In addition, fibrates, which are prescribed to patients with moderate to severe hypertriglyceridemia, may increase the risk for pancreatitis for patients whose triglyceride levels fall below 400 mg/dL, the threshold used for the prescribing guidelines.
Dr. Preiss and colleagues sought to determine the association between incident pancreatitis and lipid-lowering statins and fibrates by conducting meta-analyses of relevant, published and unpublished, large, randomized clinical trials.
The researchers included 28 randomized clinical trials (21 statin-related trials and 7 studies evaluating fibrates) that involved at least 1000 patients, with a minimum follow-up of 1 year. Unpublished data from the Helsinki Heart Study and its smaller ancillary study were included in the analysis.
Results From Statin and Fibrate Studies
Twenty-one randomized clinical trials of statin therapy provided data on 153,414 participants who were followed up for a mean of 4.3 years. Some 465 participants developed pancreatitis, of whom 204 were assigned statins (risk ratio [RR], 0.79; 95% confidence interval [CI], 0.65 - 0.95; I ², 0%; P = .01) compared with 261 who received placebo.
In 7 randomized clinical trials of fibrate therapy involving 40,162 participants who were followed up for a mean of 5.3 years with baseline averages of triglycerides ranging from 145 to 184 mg/dL; 144 participants developed pancreatitis, of whom 84 were assigned fibrates (RR, 1.39; 95% CI, 1.00 - 1.95; I ², 0%; P = .053)
"This report of pooled randomized trial data demonstrates that use of statin therapy was associated with a reduction in the number of patients developing pancreatitis," the authors write. "However, we did not demonstrate an association between use of fibrate therapy and risk of pancreatitis," they add.
Vijay P. Singh, MD, an assistant professor in the Division of Gastroenterology, Hepatology, and Nutrition at the University of Pittsburgh's School of Medicine in Pennsylvania, told Medscape Medical News it is "an interesting study."
"It simply says control your triglycerides and your risk of pancreatitis goes down," Dr. Singh said. "The statins are showing their benefit.... They're doing what they're supposed to do."
Dr. Singh questioned why Dr. Preiss and colleagues focused their discussion on a narrow band of slightly elevated triglyceride levels (145 - 184 mg/dL) when some of the studies' inclusion criteria admitted patients with levels as high at 750 mg/dL.
Focus on Pancreatic Cancer?
Although the authors suggest that their "hypothesis generating" results could be followed up with a trial comparing fibrates and statins for preventing pancreatitis in patients with severe hypertriglyceridemia, Dr. Singh says chronic pancreatitis also carries the risk of causing pancreatic cancer.
"Maybe they should look at pancreatic cancer," he told Medscape Medical News. "That is the thing that has no treatment and is a 99% killer."
Among the study's limitations, pancreatitis was not a prespecified end point in the trials, which had been designed to investigate the effect of lipid-modifying therapies on cardiovascular events. The study authors were unable to separate reports of pancreatitis into acute and chronic cases, and they lacked access to individual patient data. Because the trials under study tended to exclude patients with marked hypertriglyceridemia, the findings may not be generalizable to those patients.
"In those with slightly elevated triglyceride levels, statins appear better supported by the available data than fibrates for preventing pancreatitis," the authors conclude. "Lifestyle modifications also remain important to improve lipid profiles in such individuals."
Although the meta-analysis was not funded by external sources, one author received grant support from the British Heart Foundation and the majority of trials included in the meta-analysis were funded partly or wholly by industry. Authors report receiving honoraria from Pfizer; receiving consultant fees from Amgen Inc, Pfizer, Merck, Genzyme, Vascular Biogenics, ISIS, Boston Diagnostics, and AstraZeneca; receiving speakers' honoraria, honoraria for advisory board participation, consulting fees, or research or travel grants from Abbott/Solvay, Schering Plough, Pfizer Canada, Merck, AstraZeneca, Amgen, Roche, Sharpe & Dohme, Bristol-Myers Squibb, Eli Lilly, Pfizer, Solvay, and Novartis; participating in clinical trials funded by Pfizer; and being listed as a co-inventor on patents held by the Brigham and Women's Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease and diabetes that have been licensed to AstraZeneca and Siemens. Dr. Singh has disclosed no relevant financial relationships.source.medscape