According to David Preiss, MD, PhD, of the University of Glasgow in Scotland, pooled data from 113,800 participants in studies comparing placebo with standard-dose statins indicated that the risk of pancreatitis was lower by 23% (relative risk 0.77, 95% CI 0.62 to 0.97, P=0.03).
In addition, data from five trials of intensive versus moderate statin dosing, with a total of about 40,000 patients, showed a lower incidence of pancreatitis with high doses, although the difference did not reach statistical significance (RR 0.82, 95% CI 0.59 to 1.12, P=0.21).
A third analysis of seven placebo-controlled trials of fibrate drugs showed no such relationship, Preiss and colleagues found. In fact, the data from some 40,000 trial participants showed a trend toward increased risk of pancreatitis with fibrates (RR 1.39, 95% CI 1.00 to 1.95, P=0.053).
The findings on statins contradict a number of previous case reports and epidemiologic studies that had suggested increased risk of pancreatic inflammation with statins.
Preiss and colleagues wrote, "Although we cannot completely exclude the possibility that statin therapy may lead to very occasional idiosyncratic cases of pancreatitis, the randomized trial data appear reassuring." They also noted that animal studies have shown that statins may actually alleviate acute and chronic pancreatitis.
Preiss and colleagues reviewed the literature for controlled trials of statins with at least 1,000 participants, in which numbers of pancreatitis cases were either reported or could be obtained directly from the investigators.
A total of 21 trials met the inclusion criteria. Median follow-up in these studies ranged from 1.9 to 6.7 years. The largest was the so-called Heart Protection Study, reported in 2002, with more than 20,000 patients; the smallest was GREACE, published the same year, with 1,600 participants.
The same criteria were applied to trials of fibrates, yielding seven trials. Six of them involved monotherapy with clofibrate, gemfibrozil, bezafibrate, or fenofibrate. The seventh was the ACCORD Lipid study that tested a combination of fenofibrate plus simvastatin versus the statin drug and placebo. Most of the studies excluded patients with very high triglycerides. Mean baseline triglyceride levels ranged from 118 to 187 mg/dL.
Relatively few pancreatitis cases were seen in the trials -- among the nearly 200,000 patients in all the trials, a total of 608 developed the condition. Not surprisingly, none of the individual trials showed a significant difference in pancreatitis risk with the interventional drug treatment versus placebo or active control. But some showed strong trends suggestive of a protective statin effect.
However, because of the small numbers of pancreatitis cases identified in the studies, the researchers cautioned that their findings should be regarded as "hypothesis-generating" for statins as well as fibrates. They also recommended that a trial of statins versus fibrates in patients with severely elevated triglycerides "would be clinically valuable."
- Note that an analysis of seven placebo-controlled trials of fibrate drugs showed no reduction in the rate of pancreatitis.
- The risk of pancreatic inflammation was reduced in patients with normal or mildly increased triglycerides when they took statin drugs.
Preiss D, et al "Lipid-modifying therapies and risk of pancreatitis: a meta-analysis" JAMA 2012; 308: 804-811. Aug. 22, 2012