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

• Authors: François Mach, Geneva University; Kausik K Ray, Imperial College London; Olov Wiklund, University of Gothenburg; Alberto Corsini, University of Milan; Alberico L Catapano, University of Milan; Eric Bruckert, National Institute for Health and Medical Research; Guy De Backer, University Hospital Ghent; Robert A Hegele, University of Western Ontario; G Kees Hovingh, Academic Medical Center; Terry A Jacobson, Emory University; Ronald M Krauss, Children's Hospital Oakland Research Institute; Ulrich Laufs, University of Leipzig; Lawrence A Leiter, University of Toronto; Winfried März, University of Heidelberg; Børge G Nordestgaard, Copenhagen University; Frederick J Raal, University of Witwatersrand; Michael Roden, Heinrich Heine University; Raul D Santos, University of São Paulo; Evan A Stein, Metabolic and Atherosclerosis Research Center; Erik S Stroes, Academic Medical Center; Paul D Thompson, Hartford Hospital; Lale Tokgozoglu, Hacettepe University; Georgirene D Vladutiu, The State University of New York; Baris Gencer, Geneva University; Jane K Stock, European Atherosclerosis Society; Henry N Ginsberg, Columbia University; M John Chapman, National Institute for Health and Medical Research
• Journal Title: EHJ Cardiovascular Imaging / European Heart Journal - Cardiovascular Imaging
• Volume: Volume 39, Number 27
• Publisher: Oxford University Press (OUP): Policy B - Oxford Open Option B | 2018-07-14, Pages 2526-2539
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1093/eurheartj/ehy182
• Subjects: Health Sciences, Medicine and Surgery; Health Sciences, General
• Keywords: Science & Technology; Life Sciences & Biomedicine; Cardiac & Cardiovascular Systems; Cardiovascular System & Cardiology; Statin; Adverse effects; Glucose homeostasis; Metabolic syndrome; Cognitive function; Renal function; Liver function; Haemorrhagic stroke; Cataract; CHRONIC KIDNEY-DISEASE; INDUCED LIVER-INJURY; PLACEBO-CONTROLLED TRIAL; DENSITY-LIPOPROTEIN CHOLESTEROL; RANDOMIZED CONTROLLED-TRIALS; RECEPTOR-MEDIATED ENDOCYTOSIS; PCSK9 INHIBITOR EVOLOCUMAB; MRC/BHF HEART PROTECTION; TYPE-2 DIABETES-MELLITUS; ALL-CAUSE MORTALITY

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.