Statins in the Real World: Concerns, Conundrums, and Controversy
ACCEL | Do statins make you stupid? That's the question The New York Times asked on February 8, 2008—and it's still being debated. The cognitive effects of statins were just one of the concerns, conundrums, and controversies addressed at a 2014 American College of Cardiology (ACC) session on real-world issues relating to statin use. The session was co-chaired by Neil J. Stone, MD, first author of the recent ACC/American Heart Association (AHA) guidelines on the treatment of blood cholesterol to reduce cardiovascular risk.1
Seth S. Martin, MD, of Johns Hopkins Medicine, discussed the topic in his talk, "I am Forgetting the Title of My Talk: Are Statins to Blame?" The randomized controlled University of California San Diego (UCSD) Statin Effects Study was reported as finding that 422 (59%) of 714 patients taking statins reported cognitive and/or memory problems.2 Yet, if you read the abstract of the meeting presentation, Golomb et al. concluded: "Findings provide reassurance that low-dose statins confer little average cognitive impact with short-term use in a generally healthy population," although "possible effect modification was provisionally supported." The investigators suggested future studies evaluate subgroups that have the potential for differential statin effects and assess the higher doses of statins that are being increasingly used in lipid therapy.
However, a subsequent survey of 171 of the UCSD study participants suggested that 128 patients (75%) experienced cognitive adverse drug reactions, which the authors said were "determined to be probably or definitely related to statin therapy."3 Of 143 patients (84%) who ceased statin therapy, 128 (90%) reported improvement in cognitive problems, sometimes within days of statin discontinuation; in some cases, the authors noted "a diagnosis of dementia or Alzheimer's disease reportedly was reversed." Nineteen patients whose symptoms improved or resolved after discontinuation of statin therapy and who underwent re-challenge with a statin exhibited cognitive problems again (multiple times in some).
In 2012, the US Food and Drug Administration (FDA) expanded the warning section of the label for all statins, stating that statin use may increase cognitive decline. This was despite the FDA noting:
The post-marketing adverse event reports generally described individuals >50 years who experienced notable, but ill-defined memory loss or impairment that was reversible upon discontinuation of statin therapy.
Time to onset of the event was highly variable, ranging from 1 day to years after statin exposure. The cases did not appear to be associated with fixed or progressive dementia.
The review did not reveal an association between the adverse event and the specific statin, the age of the individual, the statin dose, or concomitant medication use.
Data from the observational studies and clinical trials did not suggest that cognitive changes associated with statin use are common or lead to clinically significant cognitive decline.
Shortly thereafter, a State-of-the-Art Review in JACC found: "After careful consideration of all discussed scientific evidence, we conclude that there is no increased risk of cognitive decline [with statin]."4 Indeed, Jukema et al. stated, "Clinical practice for statin therapy should not be changed on the basis of the most recent Food and Drug Administration informational warnings."
A few months later, Dr. Martin and colleagues published a meta-analysis evaluating 23,443 patients with a mean statin exposure duration of 3 to 24.9 years.5 In patients without baseline cognitive dysfunction, short-term data were most compatible with "no adverse effect of statins on cognition, and long-term data may support a beneficial role for statins in the prevention of dementia." The latter is based on pooled results suggesting a 29% reduction in incident dementia in statin-treated patients (hazard ratio = 0.71; 95% CI 0.61-0.82).
That same year, results of a systematic review indicated that published data do not suggest an adverse effect of statins on cognition; however, the authors acknowledged "the strength of available evidence is limited, particularly with regard to high-dose statins."6 Consequently, they noted, larger and better-designed studies are needed to draw unequivocal conclusions about the effect of statins on cognition.
As for the message for the 200 million people worldwide taking statins, Dr. Martin said "if—and that's a big if—memory problems occur with statins, they are very rare. You are more likely to get a benefit of protection from dementia when taking a statin for many years."
- Stone NJ, Robinson JG, Lichtenstein AH, et al. J Am Coll Cardiol. 2014;63:2889-934.
- Golomb BA, Dimsdale JE, White HL, Criqui MH. Circulation. 2006;114:II 289 (Abst. 1501).
- Evans MA, Golomb BA. Pharmacotherapy. 2009;29:800-11.
- Jukema J, Cannon CP, de Craen AM, et al. JAm Coll Cardiol. 2012;60:875-81.
- Swiger KJ, Manalac RJ, Blumenthal RS, et al. Mayo Clin Proc. 2013;88:1213-21.
- Richardson K, Schoen M, French B, et al. Ann Intern Med. 2013;159:688-97.
Keywords: CardioSource WorldNews Interventions
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