EAS Consensus Panel: CV benefits of statin therapy far outweigh any adverse effects

Introduction 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

References

Find this article online at Eur Heart J