From The Annals of Pharmacotherapy
Carlos H Rojas-Fernandez PharmD; Jean-Christy F Cameron BSc(Pharm)
A Narrative Review and Clinical Recommendations
Abstract and Introduction
Abstract
Objective: To explore the impact of statin use on cognition.
Data Sources: A literature search was performed using MEDLINE (1950-November 2011), EMBASE (1980-November 2011), and the Cochrane Library (1960-November 2011) using the search terms "cognition/drug effects," "delirium, dementia, amnestic, cognitive disorders/chemically induced," "memory disorders/chemically induced," "hydroxymethylglutaryl-CoA reductase inhibitors/adverse effects," and "hydroxymethylglutaryl-CoA reductase inhibitors." A bibliographic search on included references was also conducted.
Study Selection and Data Extraction: Studies were included for analysis if they were conducted in humans and examined the impact of statin use on cognition as either a primary or secondary endpoint; case reports and case series were also included for analysis.
Data Synthesis: Reports of statin-associated cognitive impairment were found primarily in observational studies (eg, case reports/series). One randomized controlled trial demonstrated that simvastatin impaired some measures of cognition compared to placebo. Conversely, in the majority of randomized controlled trials and observational studies, statins were found to have either a neutral or beneficial effect on cognition. Preliminary data suggest that statins that are less lipophilic (ie, pravastatin and rosuvastatin) may be less likely to contribute to cognitive impairment due to limited penetration across the blood-brain barrier. These drugs would be a logical alternative in cases where cognitive impairment secondary to another statin is suspected.
Conclusions: Despite several reports of statin-associated cognitive impairment, this adverse effect remains a rare occurrence among the totality of the literature. If statin-associated cognitive impairment is suspected, a trial discontinuation can reveal a temporal relationship. Switching from lipophilic to hydrophilic statins may resolve cognitive impairment. The vascular benefits and putative cognitive benefits outweigh the risk of cognitive impairment associated with statin use; therefore, the current evidence does not support changing practice with respect to statin use, given this adverse effect.
Data Sources: A literature search was performed using MEDLINE (1950-November 2011), EMBASE (1980-November 2011), and the Cochrane Library (1960-November 2011) using the search terms "cognition/drug effects," "delirium, dementia, amnestic, cognitive disorders/chemically induced," "memory disorders/chemically induced," "hydroxymethylglutaryl-CoA reductase inhibitors/adverse effects," and "hydroxymethylglutaryl-CoA reductase inhibitors." A bibliographic search on included references was also conducted.
Study Selection and Data Extraction: Studies were included for analysis if they were conducted in humans and examined the impact of statin use on cognition as either a primary or secondary endpoint; case reports and case series were also included for analysis.
Data Synthesis: Reports of statin-associated cognitive impairment were found primarily in observational studies (eg, case reports/series). One randomized controlled trial demonstrated that simvastatin impaired some measures of cognition compared to placebo. Conversely, in the majority of randomized controlled trials and observational studies, statins were found to have either a neutral or beneficial effect on cognition. Preliminary data suggest that statins that are less lipophilic (ie, pravastatin and rosuvastatin) may be less likely to contribute to cognitive impairment due to limited penetration across the blood-brain barrier. These drugs would be a logical alternative in cases where cognitive impairment secondary to another statin is suspected.
Conclusions: Despite several reports of statin-associated cognitive impairment, this adverse effect remains a rare occurrence among the totality of the literature. If statin-associated cognitive impairment is suspected, a trial discontinuation can reveal a temporal relationship. Switching from lipophilic to hydrophilic statins may resolve cognitive impairment. The vascular benefits and putative cognitive benefits outweigh the risk of cognitive impairment associated with statin use; therefore, the current evidence does not support changing practice with respect to statin use, given this adverse effect.
Introduction
Since their introduction in 1987, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have become the most commonly prescribed agents for the treatment of dyslipidemia. Statins are the most effective and widely used medicines to reduce low-density lipoprotein cholesterol and reduce cardiovascular events. Statins are well tolerated and have minimal adverse effects, most commonly myopathies, effects on liver enzymes, diarrhea, and rarely rhabdomyolysis. As with all drugs, some adverse effects do not manifest in clinical trials but become evident after use in larger samples and broader patient populations. For example, several case reports and case series have suggested a potential association between statins and cognitive impairment. This possible adverse effect warrants further investigation, as it is contradictory to several studies that demonstrate a potential benefit on cognition with the use of statins. Cognitive impairment can also be considered a severe adverse effect with the potential to cause other adverse outcomes such as functional impairment.
Furthermore, the incidence of statinassociated cognitive impairment has not been clearly defined, and considering the number of patients receiving statins, even uncommon adverse effects have the potential to impact a large number of people. For example, in 2002, an estimated 7.8% of the Canadian population was taking statins, which accounts for 2,447,062 Canadians. If the incidence of statin-associated cognitive impairment were only 0.1%, it would affect nearly 2500 people in Canada. Since cognitive impairment is a potentially debilitating adverse effect, it is important to better understand this risk to adequately assess the appropriateness of statins for individual patients. Additionally, although recent reports have highlighted the risk of cognitive impairment with the use of statins, few have provided a balanced discussion of this risk with the beneficial effects of these agents on both cardiovascular outcomes and possibly cognition. It is important to present the benefits and risks of these medications so that clinicians and their patients can make informed decisions.
This article explores the potential adverse effect of statins on cognition, and considers the established vascular and putative cognitive benefits of these drugs as a balance to the risk of adverse effects.
for rest of article go to http://www.medscape.com/viewarticle/762126_8
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