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Review
. 2018 Jul 14;39(27):2526-2539.
doi: 10.1093/eurheartj/ehy182.

Adverse effects of statin therapy: perception vs. the evidence - focus on glucose homeostasis, cognitive, renal and hepatic function, haemorrhagic stroke and cataract

François Mach  1 , Kausik K Ray  2 , Olov Wiklund  3   4 , Alberto Corsini  5 , Alberico L Catapano  5 , Eric Bruckert  6 , Guy De Backer  7 , Robert A Hegele  8 , G Kees Hovingh  9 , Terry A Jacobson  10 , Ronald M Krauss  11 , Ulrich Laufs  12 , Lawrence A Leiter  13 , Winfried März  14   15 , Børge G Nordestgaard  16   17   18 , Frederick J Raal  19 , Michael Roden  20   21 , Raul D Santos  22   23 , Evan A Stein  24 , Erik S Stroes  9 , Paul D Thompson  25 , Lale Tokgözoglu  26 , Georgirene D Vladutiu  27 , Baris Gencer  1 , Jane K Stock  28 , Henry N Ginsberg  29 , M John Chapman  30 ; European Atherosclerosis Society Consensus Panel
Affiliations
Review

Adverse effects of statin therapy: perception vs. the evidence - focus on glucose homeostasis, cognitive, renal and hepatic function, haemorrhagic stroke and cataract

François Mach et al. Eur Heart J. .

Abstract

Aims: To objectively appraise evidence for possible adverse effects of long-term statin therapy on glucose homeostasis, cognitive, renal and hepatic function, and risk for haemorrhagic stroke or cataract.

Methods and results: A literature search covering 2000-2017 was performed. The Panel critically appraised the data and agreed by consensus on the categorization of reported adverse effects. Randomized controlled trials (RCTs) and genetic studies show that statin therapy is associated with a modest increase in the risk of new-onset diabetes mellitus (about one per thousand patient-years), generally defined by laboratory findings (glycated haemoglobin ≥6.5); this risk is significantly higher in the metabolic syndrome or prediabetes. Statin treatment does not adversely affect cognitive function, even at very low levels of low-density lipoprotein cholesterol and is not associated with clinically significant deterioration of renal function, or development of cataract. Transient increases in liver enzymes occur in 0.5-2% of patients taking statins but are not clinically relevant; idiosyncratic liver injury due to statins is very rare and causality difficult to prove. The evidence base does not support an increased risk of haemorrhagic stroke in individuals without cerebrovascular disease; a small increase in risk was suggested by the Stroke Prevention by Aggressive Reduction of Cholesterol Levels study in subjects with prior stroke but has not been confirmed in the substantive evidence base of RCTs, cohort studies and case-control studies.

Conclusion: Long-term statin treatment is remarkably safe with a low risk of clinically relevant adverse effects as defined above; statin-associated muscle symptoms were discussed in a previous Consensus Statement. Importantly, the established cardiovascular benefits of statin therapy far outweigh the risk of adverse effects.

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Figures

Figure 1
Figure 1
Overview of the relative prevalence of the main types of adverse effects reported with statin therapy. RCT, randomized controlled trial; SPARCL, Stroke Prevention by Aggressive Reduction in Cholesterol Levels.
Figure 2
Figure 2
Factors favouring diabetogenic effects of statins and candidate mechanisms in extrahepatic tissues and pancreatic beta-cells. AKT, alpha serine-threonine-protein kinase; ATP, adenosine triphosphate; CoQ10, Coenzyme Q10, also known as ubiquinone; FBG, fasting blood glucose; GLUT, glucose transporter; HbA1c, glycated haemoglobin; HMG CoA reductase, 3-hydroxy-3-methylglutaryl coenzyme A reductase; LDLR, low-density lipoprotein receptor; NLRP3, NOD-like receptor family, pyrin domain containing 3.
Figure 3
Figure 3
Factors that may affect susceptibility to drug induced liver injury, either by influencing drug metabolism or transport mechanisms.
Take home figure
Take home figure
The cardiovascular benefit of long-term statin therapy far outweighs potential risks. ASCVD, atherosclerotic cardiovascular disease; LDL-C, low-density lipoprotein cholesterol; RCT, randomized controlled trial; SPARCL, Stroke Prevention by Aggressive Reduction in Cholesterol Levels.
None
See this image and copyright information in PMC

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