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

Abstract

AimsTo 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 resultsA 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.ConclusionLong-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.

Statins for primary prevention of cardiovascular disease and the risk of acute kidney injury

“…20,21 This tubular toxicity has been reported in rare case reports, 22 sometimes associated with tubulointerstitial nephritis. 23 Nevertheless, randomized trials have shown that statins may also have renoprotective effects, 24 especially in diabetic patients, 25 even when prescribed at high doses, or when given for prevention of contrast-induced AKI. 26,27 Of note, a metaanalysis showed similar renoprotective effects in high CVD risk patients treated with atorvastatin and rosuvastatin prescribed at commonly used doses.…”

Dyslipidaemia in adults with type 1 diabetes—when to treat?

“…Side effects were rare in large double-blind placebocontrolled trials. 14 Given the investigation results, we would favour statin use. This is in accordance with most guidelines and should be in the context of shared decision-making with the patient.…”

“…Adequately addressing the benefits and risks of statins may improve adherence. Side effects were rare in large double‐blind placebo‐controlled trials . It may be worthwhile gauging the patient's understanding and perceived risk.…”

Statin Intolerance Clinical Guide 2018

“…These six stains are associated with mildly to moderately elevated transaminase levels, and according to a large-scale study conducted in Europe and the US, in many cases they appear in 0.5% to 2.0% of cases within the first three months of administration. Systematic meta-analyses of 135 RCTs that included a total of 246,000 patients reported that statins have approximately 50% higher risk of elevated transaminase levels than controls and placebos, and that in the cases of Atorvastatin, Rosuvastatin, and Simvastatin, the enzyme elevations are dose-dependent [39][40][41] . However, the overall frequency of 0.5% to 2.0% was nearly the same as that for the placebo.…”