Statins' benefits beyond heart health aren't clear-cut, analysis says

The drugs are commonly prescribed to prevent heart disease in individuals above a certain risk level, but the new analysis -- published Monday in the journal Annals of Internal Medicine -- looked at 278 other health conditions and effects.

"I was surprised by the amount of outcomes we identified to have been linked with statins," study author Evropi Theodoratou, a researcher at the University of Edinburgh, wrote in an email. "However, we only identified a dearth of convincing evidence that statins had a major role" in these outcomes.

The analysis found limited evidence of positive outcomes related to cancer, dementia, kidney disease and chronic obstructive pulmonary disease, known as COPD. But only one of these outcomes was significant in a randomized trial -- lower all-cause mortality in patients with chronic kidney disease -- and the authors say it could still be driven by the drugs' impact on cardiovascular disease; the two often go hand in hand.

"Clinical guidelines already recognize the benefits of statins in preventing cardiovascular events in patients with chronic kidney disease who are not receiving dialysis. On the other hand, clinical guidelines currently do not indicate the use of statins to improve cancer prognosis or COPD," Theodoratou said. "I am not aware of any serious efforts by doctors to redefine these guidelines."

More testing needed

More than a quarter of Americans over 40 take a statin, the most common type of cholesterol-lowering medication, according to a 2014 report from the US Centers for Disease Control and Prevention. Different statins are sold under brand names such as Lipitor and Crestor.

Michael Pencina, vice dean for data science and information technology at the Duke University School of Medicine, said the analysis was important because people will invariably be on statins for long periods of time for their heart health, but the question remains: What else could those statins be doing, good or bad?

"I think what we are generally missing in the whole statin discussion is the fully integrated risk-benefit analysis," said Pencina, who was not involved in the new study.

Researchers say this doesn't mean these outcomes aren't necessarily null; they just haven't been sufficiently tested yet.

"From the breast cancer perspective, there's a great deal of very consistent evidence both from laboratory models and from epidemiologic studies that demonstrates a lower risk of breast cancer recurrence" for people on a certain type of statins, said Thomas Ahern, an assistant professor of surgery at the Larner College of Medicine at the University of Vermont. Ahern has studied the link between statins and breast cancer but was not involved in the new analysis.

Ahern noted that the new paper omits studies conducted in a lab, which could contain important information. (The study says there is "suggestive" evidence gleaned from observational analyses that recurrence-free breast cancer survival is linked to statins.)

"When it comes down to it, I don't think that their conclusions differ fundamentally from our view, which is that it's high time that statins be definitively tested in breast cancer survivors in an appropriately designed clinical trial," Ahern said.

Pros and cons

Some patients on statins report a number of side effects, such as muscle pain, increased blood sugar and memory problems. But the majority of patients have no side effects at all.

"There was a modest increase in diabetes among people treated with statins, but this evidence is not enough to justify not taking the drugs, which is in accordance to expert consensus," Theodoratou said.

The new analysis detected "no significant effects" of the drugs on a range of side effects, including muscle pain. Theodoratou described this as "reassuring" but cautioned that "we cannot exclude the possibility that some of these harms such as muscle pain may be too rare to rule out with certainty.

"We did not find strong evidence for an association but not all of the original studies had adequately reported side effects. So, we cannot conclude that the drugs do not cause muscle pain," she said.

Doctors have said certain people are "miserable" taking statins, and muscle pain in particular is a commonly reported side effect. The disconnect between these experiences and the new analysis could be explained by how individual studies select patients or how difficult it might be to tell whether muscle symptoms are actually a result of statins, according to the authors.

Experts have described how, the more patients are aware -- and perhaps fearful -- of statins and their side effects, the more likely they are to report those side effects. This phenomenon is known as the nocebo effect, the opposite of the placebo effect.

The new paper reviews previous metaanalyses -- Pencina called it a "summary of summaries" -- but does not closely evaluate individual studies, which may have their own selection bias, inedequate follow-up, missing data, and potential financial conflicts and industry influence.

While studies funded by drugmakers tend to produce more effective outcomes than independently funded studies, some have refuted the effect of industry bias on statin research.

Theodoratou says that differences in how studies were designed and potential bias may explain why some findings, like Alzheimer's, were significant in observational studies but not randomized trials. She also noted that how researchers rated the evidence is mostly based on "artbitrary thresholds, and currently no gold standard exists ... to truly quantify the risk of bias."

Ahern said, "they're very transparent about that," adding that the value in this analysis is figuring out where scientists should look next to better understand the impacts of statins.

"Which of these off-target, beneficial effects should we pour our research dollars and effort into pursuing?" he asked.

Similarly, Pencina called the new study "hypothesis-generating" and said it could be useful in better weighing the pros and cons of statins for people who are taking them for heart health.

Health experts say that no pill, including statins, should replace a healthy diet, exercise and avoiding smoking -- whose benefits extend well beyond heart health, research shows.