EAS Consensus Panel: CV benefits of statin therapy far outweigh any adverse effects
Adverse effects of statin therapy: perception vs. the evidence – focus on glucose homeostasis, cognitive, renal and hepatic function, haemorrhagic stroke and cataract
Literature - Mach F, Ray KK, Wiklund O, et al., European Atherosclerosis Society Consensus Panel - Eur Heart J, Published: 27 April 2018. https://doi.org/10.1093/eurheartj/ehy182Introduction and methods
The efficacy of statin treatment to lower LDL-c and to prevent both first and recurrent CV events is well-established [1-3]. Also, large randomized controlled trials (RCTs) have clearly demonstrated the benefit/risk ratio of this treatment [3,4]. In light of the possible advent of a statin-containing polypill, thus potentially more widespread use, the evidence related to possible unintended effects of long-term statin therapy needs critical appraisal.
This is an objective appraisal of adverse effects attributed to statins, in order to differentiate the perception from the reality of potential risks associated with statin therapy, with a focus on glucose homeostasis, and cognitive, renal and hepatic function, as well as the risk of hemorrhagic stroke and cataract.
Statin-associated muscle symptoms (SAMS) are the most commonly reported adverse effects in clinical practice. It is often debated whether SAMS represents real or nocebo effects, as a consequence of negative expectations. The ASCOT-LLA study published that a nocebo effect may explain the higher incidence of SAMS in observational studies vs RCTs [5]. Others have described a higher rate when treatment was blinded, as compared with when patients knew they were on a statin. From these different observations, it may be concluded that clinicians should be cautious about attributing muscle symptoms to statin therapy, without further investigation of the origin of symptoms.
This article is the report of a literature search covering 2000-2017, and the content resulted from a consensus of considered opinions and insights of the expert members of the panel. The article elaborates on the available evidence. SAMS were discussed before in a previous EAS Consensus Document [6]. Here, we summarize the take home messages per topic.
Main results
- Effects on glucose homeostasis: RCTs and genetic studies indicate that statin treatment is associated with a modest increase in the risk of new-onset diabetes, but the preventive effect on CVD effects is larger. The risk of developing new-onset diabetes is higher in people with features of metabolic syndrome or prediabetes. Patients should be reassured that the benefits of statins in preventing CVD events far outweigh the potential risk from elevation in plasma glucose, especially in those with elevated HbA1c.
- Cognitive function: Statin treatment does not adversely affect cognitive function. At very low LDL-c levels attained with combination therapy, no signal was seen for any adverse effect on cognitive function, which is supported by Mendelian Randomization studies.
- Effects on renal function: No clinically significant deterioration of renal function is associated with statin therapy. In patients on high-intensity statins with severe kidney dysfunction, dose reduction based on eGFR may be prudent.
- Effects on hepatic function: Mild ALT elevation in isolation in asymptomatic statin users is not clinically relevant. Clinically apparent liver injury with statin therapy is very rare. Routine periodic monitoring of liver enzymes is not justified. Liver enzymes should only be measured in rare patients who develop symptoms suggestive of hepatotoxicity.
- Hemorrhagic stroke: Statin treatment lowers the risk of first or recurrent hemorrhagic stroke. No change in statin treatment in patients with a history of CVD is indicated.
- Cataract: Statin treatment is not associated with development of cataract.
Conclusion
Based on the objective appraisal of the literature on potential adverse effects of statins, the Consensus Panel concludes that statin treatment is remarkably safe. Although long-term statin treatment confers a modest risk of new onset DM, per case of DM, five new CVD events are avoided with statin therapy.
The authors conclude by saying that clinicians should be reassured by the long-term safety of statins, and the low risk of clinically relevant adverse effects. The established CV benefits of statin therapy far outweigh the risk of any adverse effect.
References
1. Piepoli MF, Hoes AW, Agewall S, et al., 2016 European Guidelines on cardiovascular disease prevention in clinical practice: the Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J 2016;37:2315–2381.
2. Ference BA, Ginsberg HN, Graham I, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J 2017; 38:2459–2472.
3. Collins R, Reith C, Emberson J, et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet 2016;388:2532–2561.
4. Cholesterol Treatment Trialists’ (CTT) Collaboration et al. Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials. Lancet 2015;385:1397–1405.
5. Gupta A, Thompson D, Whitehouse A et al. Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm (ASCOT-LLA): a randomised doubleblind placebo-controlled trial and its non-randomised non-blind extension phase. Lancet 2017; 389:2473–2481.
6. Stroes ES, Thompson PD, Corsini A, et al; European Atherosclerosis Society Consensus Panel. Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. Eur Heart J 2015;36:1012–1022.
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