A new systematic review of published literature has found no link between statin use and impaired cognition, despite the US Food and Drug Administration's (FDA's) warning last year that statins may be associated with memory loss or confusion.
"I find that the data that's currently available is quite reassuring," said reviewer Emil M. deGoma, MD, medical director, Preventive Cardiovascular Program, University of Pennsylvania, Philadelphia. "I don't think that there's a significant association between statins and cognitive function."
However, he added that further research is needed in the form of larger randomized trials.
The review was published online November 18 in the Annals of Internal Medicine.
Statement a Surprise
The review was prompted in part by the FDA statement, which came as something of a surprise to many physicians, said Dr. deGoma. "Many in the medical community wondered what was the body of evidence, and what was the rationale, for that decision. It's one thing to say that a medication may lead to a particular side effect; it's another when the FDA provides an official statement behind that."
Although the methods and detailed findings of the FDA analysis haven't been made available, there's some indication that substantial weight was placed on case reports, according to the review authors. It may be that the FDA "is privy" to unpublished data or other information unavailable to the reviewers, said Dr. deGoma.
The new meta-analysis included 25 studies (3 randomized controlled trials, 16 cohort studies, 4 case-control studies, and 2 cross-sectional studies). Reviewers looked at the incidence of dementia or mild cognitive impairment and effects on cognitive performance using scores from a battery of tests.
Among statin users, low-quality evidence suggested no increased incidence of Alzheimer's disease and no difference in cognitive performance in procedural memory, attention, or motor speed. Moderate-quality evidence suggested no increased incidence of dementia or mild cognitive impairment or any change in cognitive performance related to global cognitive performance scores, executive function, declarative memory, processing speed, or visuoperception.
"In each of those areas, we did not identify a signal suggesting an adverse effect of statins on cognition," said Dr. deGoma.
The reviewers also investigated the FDA's postmarketing surveillance database to calculate reported rates of cognitive adverse events for statins, losartan (an angiotensin-receptor blocker), and clopidogrel (an adenosine diphosphate receptor inhibitor). They found that reporting rates were similar for the 3 drugs.
Neither losartan nor clopidogrel has been associated with cognitive impairment, noted the authors. "To our knowledge, no studies to date have suggested memory loss with these medications, and the FDA has not issued a formal warning for these drugs," they wrote.
Although the review results are positive and reassuring, Dr. deGoma noted that any medication can cause side effects. "I'm not saying it can never occur; the question is more, does it occur often enough that it should be a signal on our radar when we talk to patients and weigh in the risks and benefits of starting a medication?"
The review did have some limitations, including sparse data on the cognitive effects of statins at high doses and the lack of well-powered randomized trials.
"We still need more large randomized trials looking specifically at cognitive endpoints, and ideally using higher doses of statins," said Dr. deGoma.
The systematic review is particularly timely now that the American Heart Association and the American College of Cardiology has released new cholesterol guidelines that eliminate target low-density lipoprotein thresholds. This could result in more patients being prescribed statins.
"I think it's anticipated that more people will qualify for statins based on the new outlook in the new guidelines," said Dr. deGoma. "It's reassuring in that regard; I don't think we have to be significantly concerned about cognitive impairment."
He also noted that no link between statin use and cognitive decline was seen with moderate-dose statin therapy, and it's the initiation of statins in this dose range for which the new guidelines will mostly likely have an impact.
To comment on the new review, Medscape Medical News approached Carlos R. Fernandez, PharmD, Schlegel Research Chair in Geriatric Pharmacotherapy, University of Waterloo, Kitchener, Ontario, Canada, who carried out a similar review and is a member of an expert panel of the American Lipid Association investigating statins and cognition.
Dr. Fernandez praised the review. "I like the way they separated out the different cognitive domains, and quite properly concluded that there's not a real signal there, at least on average for most people."
He added that no signal seems to exist "in either direction," referring to some earlier studies that had suggested statins may actually be cognitively protective.
The reviewer's assessment of the FDA adverse event database, which found an "almost identical" rate of complaints for statins, losartan, or clopidogrel, was "very clever," commented Dr. Fernandez.
"It doesn't look like any harm is being done and certainly the benefit of these drugs where they're indicated is very clear," he said. "All you can say if you look at the literature right now is that there are some case reports out there, but case reports are limited for obvious reasons."
Dr. Fernandez said he's concerned that patients and doctors get correct information. "My biggest fear and that of many of my colleagues is that the wrong information gets out there and people stop taking these medications; that they won't take them based on an unfounded fear."
He agreed that high-quality studies looking at cognition and statin use are needed but said such studies may never come about, considering the cost and the fact that the risk for cognitive effects is probably small and largely reversible.
Dr. deGoma has disclosed no relevant financial relationships.
Ann Intern Med. Published online November 19, 2013. Abstract
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Cite this: No Link Between Statins and Cognitive Decline - Medscape - Nov 18, 2013.