August 24th, 2012
Is Bad News About Fibrates Getting Buried?
Harlan M. Krumholz, MD, SM
This week JAMA published a meta-analysis on lipid-modifying therapies and the risk for pancreatitis. It was conducted by an honor roll of investigators, including LaRosa, Pedersen, Ridker, Kjekshus, McMurray, and others. The conclusion of the abstract says, “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.”
A casual reader might miss something even more interesting. The authors also looked at the much-maligned fibrates. You know, the drugs that many people touted to prevent pancreatitis in patients with elevated triglyceride levels. Well, the curious thing is that in the pooled analysis of the fibrate trials, these drugs were associated with a borderline significant 39% increase in the risk of pancreatitis (risk ratio, 1.39; 95% CI, 1.00–1.95) — a concerning finding, even if merely hypothesis-generating. Compare that with the 23% reduction in risk with statin therapy (RR, 0.77; 95% CI, 0.62–0.97).
The discussion notes that “no convincing trial data exist to support use of any agents for prevention of pancreatitis in this situation” (moderate elevation in triglyceride levels). The authors also acknowledge, appropriately, that their results should indeed be considered hypothesis-generating.
I agree this analysis has limitations, but what evidence we do have suggests, at least, that fibrates may be associated with a higher — not a lower — risk for pancreatitis. Fibrates, with about $2 billion dollars in sales annually, have yet to be shown in a trial to reduce risk. The results of the current meta-analysis therefore raise questions about their use.
What’s your view on the use of fibrates? Do you think the fibrate data in this meta-analysis get enough play in the article?
2 Responses to “Is Bad News About Fibrates Getting Buried?”
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I fully agree. While I still use these drugs in patients with atherogenic dyslipidemia associated with metabolic syndrome (which is the only setting in which they have been proven to work – at least in 5 separate subgroup analyses), I am moving more and more towards carbohydrate restriction in this setting, rather than “fibrate first”. Getting a patient to reduce their intake of starch and sugar can dramatically reduce their triglycerides, boost their HDL cholesterol, reduce markers of serum glycemia, inflammation, blood pressure and numerous other adverse bio-processes. After successful lifestyle change, I then stop the fibrate and monitor closely.
Actually, I believe it was the WHO trial on clofibrate which reported back in 1979 that patients on clofibrate were dying at higher rates from complicated cholecystitis and gallstone pancreatitis. So these data are not that new. In FIELD, we also saw increases in pancreatitis and pulmonary embolism, as well as a trend toward increased non-cardiac mortality. All drugs are toxins to a certain extent, but these problems have not markedly affected prescribing practices as they should have.
In summary, let’s push effective and efficient lifestyle modification practices, and reserve fibrates for severe hypertriglyceridemia or those who cannot successfully modify their lifestyle and still fit the metabolic syndrome phenotype.
I rarely prescribe fibrates. Nonetheless, I would be curious to know if this meta-analysis merely reflects a preference for fibrate therapy in patients with high triglycerides, and therefore a higher baseline risk for pancreatitis, rather than a causal relationship.