Atorvastatin and Memory: Does It Affect Cognition?

What the Lipitor label says about memory

The label lists cognitive impairment, including memory loss and confusion, among reactions reported after approval [1]. It notes that postmarketing reports come from a population of uncertain size, so a frequency and a causal link to the drug cannot be reliably established from them [1].

Memory complaints are not in Warnings and Precautions, which covers myopathy and rhabdomyolysis, immune-mediated necrotizing myopathy, liver injury, increases in HbA1c and fasting glucose, and more hemorrhagic stroke at 80 mg after a recent hemorrhagic stroke [1].

The pooled safety table covers 17 placebo-controlled trials: 8,755 patients on atorvastatin at any dose and 7,311 on placebo, median 53 weeks [1]. Insomnia was reported in 3.0% of patients on atorvastatin and 2.9% on placebo [1]. Nightmares appear among the other reactions reported in those trials, without a rate [1].

What the atorvastatin trials measured

SPARCL randomized 4,731 people who had a stroke or transient ischemic attack in the previous one to six months, with no known coronary heart disease and LDL cholesterol of 100 to 190 mg/dL, to atorvastatin 80 mg daily or placebo for a median 4.9 years [2]. The primary endpoint was a first fatal or nonfatal stroke, which occurred in 265 patients (11.2%) on atorvastatin versus 311 (13.1%) on placebo (HR 0.84, 95% CI 0.71 to 0.99); ischemic strokes numbered 218 versus 274 and hemorrhagic strokes 55 versus 33 [2]. TNT compared 80 mg with 10 mg in 10,001 people with stable coronary heart disease, and its primary endpoint was a first major cardiovascular event [4].

The 80 mg dose and hemorrhagic stroke

The label's brain-related warning is about bleeding. In a post-hoc analysis of SPARCL, hemorrhagic stroke occurred in 2.3% of patients on atorvastatin 80 mg versus 1.4% on placebo (HR 1.68, 95% CI 1.09 to 2.59) [1]. Fatal hemorrhagic strokes were similar (17 versus 18) and non-fatal ones higher on atorvastatin (38 versus 16), and participants who entered the trial after a hemorrhagic stroke had rates of 16% versus 4% [1]. Ischemic stroke was lower on atorvastatin, 9.2% versus 11.6% [1]. The label says to consider the risk and benefit of 80 mg in someone who has had a recent hemorrhagic stroke [1]. These are stroke outcomes, so they do not by themselves show how atorvastatin affects memory or thinking [1].

Dose range

The label gives a usual adult starting dose of 10 mg or 20 mg once daily, with a range of 10 mg to 80 mg; patients who need LDL cholesterol to fall by more than 45% may start at 40 mg [1].