AHA: Some Statins Can Disrupt Sleep

If patients taking simvastatin (Zocor) develop sleep disturbances, changing statins may be a good idea, researchers suggested at the AHA scientific meeting. Simvastatin modestly but significantly reduced sleep quality and increased sleep problems compared with pravastatin (Pravachol), according to a large study of subjective sleep measures reported at the American Heart Association meeting.
"This provides tentative corroboration for long-standing concerns that lipophilic statins may affect sleep in some individuals," said Beatrice Golomb, M.D., Ph.D., of the University of California at San Diego, who reported the findings of a study of 1,016 patients.

Simvastatin is the most lipophilic of the statins, she noted. This may allow the drug to more readily cross the blood-brain barrier and impact serotonin or other sleep-related factors compared with statins such as pravastatin, which is the most hydrophilic.

Among other statins, lovastatin is lipophilic, rosuvastatin (Crestor) may be hydrophilic, and atorvastatin (Lipitor) is considered intermediate.

For patients who develop sleep problems after starting on a statin, "it might be prudent to switch to a different statin," Dr. Golomb said.

Sleep has not generally been reported as an adverse event in large efficacy trials, although case series and smaller trials have indicated insomnia, nightmares and other sleep disturbances may be more common with some statins.

To test sleep outcomes prospectively, the researchers conducted a double-blind trial in which 1,000 men and postmenopausal women were randomized to placebo or equivalent, or modest doses of pravastatin (40 mg) or simvastatin (20 mg).

At baseline, participants had LDL cholesterol in the 115 to 190 mg/dl range, for which statin treatment was considered optional at the time. None had known cardiovascular disease, diabetes, or a fasting blood glucose of 140 mg/dl or higher. None was on statin therapy before enrollment in the study.

Sleep quality and sleep problems were similar between treatment groups at baseline. At six months, sleep quality dropped in all three groups, but there were significant differences between them.

On-treatment sleep quality remained above average with pravastatin and placebo (mean score 15.79 and 15.50 on a 30-point visual analog Leeds scale), whereas it was below average with simvastatin (mean 14.67, P=0.003 versus pravastatin and P=0.026 versus placebo).

Sleep problems worsened during treatment to a greater degree with simvastatin than with pravastatin or placebo (0.21 versus 0.098 and 0.074 on a two-point scale from zero change to much worse). After adjustment for baseline problems with sleep, the differences were significant (P=0.038 versus pravastatin and P=0.007 versus placebo).

Sleep quality was significantly linked to tiredness and irritability, whereas sleep problems were correlated with tiredness, irritability, and cognition (all P0.001).

More patients taking simvastatin reported sleep as much worse than at baseline than did patients on placebo (P=0.015), and a similar trend was seen compared with pravastatin (P=0.093).

However, the researchers could not pin down what specific sleep changes were occurring.

Practice Pearl:

• Explain to interested patients that the study supports an effect of statins on sleep, particularly lipophilic agents such as simvastatin.

These results were presented at he American Heart Association’s Scientific Sessions 2007 in Orlando, Fla.

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