Statin Safety and Associated Adverse Events: A Scientific Statement From the American Heart Association

Abstract

One in 4 Americans >40 years of age takes a statin to reduce the risk of myocardial infarction, ischemic stroke, and other complications of atherosclerotic disease. The most effective statins produce a mean reduction in low-density lipoprotein cholesterol of 55% to 60% at the maximum dosage, and 6 of the 7 marketed statins are available in generic form, which makes them affordable for most patients. Primarily using data from randomized controlled trials, supplemented with observational data where necessary, this scientific statement provides a comprehensive review of statin safety and tolerability. The review covers the general patient population, as well as demographic subgroups, including the elderly, children, pregnant women, East Asians, and patients with specific conditions such as chronic disease of the kidney and liver, human immunodeficiency viral infection, and organ transplants. The risk of statin-induced serious muscle injury, including rhabdomyolysis, is <0.1%, and the risk of serious hepatotoxicity is ≈0.001%. The risk of statin-induced newly diagnosed diabetes mellitus is ≈0.2% per year of treatment, depending on the underlying risk of diabetes mellitus in the population studied. In patients with cerebrovascular disease, statins possibly increase the risk of hemorrhagic stroke; however, they clearly produce a greater reduction in the risk of atherothrombotic stroke and thus total stroke, as well as other cardiovascular events. There is no convincing evidence for a causal relationship between statins and cancer, cataracts, cognitive dysfunction, peripheral neuropathy, erectile dysfunction, or tendonitis. In US clinical practices, roughly 10% of patients stop taking a statin because of subjective complaints, most commonly muscle symptoms without raised creatine kinase. In contrast, in randomized clinical trials, the difference in the incidence of muscle symptoms without significantly raised creatine kinase in statin-treated compared with placebo-treated participants is <1%, and it is even smaller (0.1%) for patients who discontinued treatment because of such muscle symptoms. This suggests that muscle symptoms are usually not caused by pharmacological effects of the statin. Restarting statin therapy in these patients can be challenging, but it is important, especially in patients at high risk of cardiovascular events, for whom prevention of these events is a priority. Overall, in patients for whom statin treatment is recommended by current guidelines, the benefits greatly outweigh the risks.

Loss-of-function genomic variants with impact on liver-related blood traits highlight potential therapeutic targets for cardiovascular disease

“…2,3 However, some pharmaceutical mechanisms of reducing CVD may increase risk of fatty liver disease or other metabolic disorders. 4,5,6 To identify potential novel therapeutic targets, which may reduce risk of CVD without increasing risk of metabolic disease, we focused on the simultaneous evaluation of quantitative traits related to liver function and CVD. Using a combination of low-coverage (5x) wholegenome sequencing and targeted genotyping, deep genotype imputation based on the TOPMed reference panel 7 , and genome-wide association study (GWAS) meta-analysis, we analyzed 12 liverrelated blood traits (including liver enzymes, blood lipids, and markers of iron metabolism) in up to 203,476 people from three population-based cohorts of different ancestries.…”

Statins and Neuropathic Pain: A Narrative Review

“…The American Heart Association published a statement in 2019 that there is ''no convincing evidence for a causal relationship'' between statins and peripheral neuropathy [94]. This stands in contrast to an older statement issued 17 years earlier by the Academy of Neurology, which reported that statins may increase the risk of peripheral neuropathy, stating patients on statins were 14 times more likely to develop neuropathy than those not taking statins [95].…”

Sekundäre Neuroprotektion beim Glaukom durch ergänzende medikamentöse Therapiekonzepte

“…Bei den Statinen ist die Diskussion um die Nebenwirkungen noch nicht abgeschlossen [201]. Besonders die Induktion eines Diabetes mellitus steht hier im Vordergrund, die aber nach der American Heart Association nur bei 0,2 % pro Jahr betragen soll [202] und somit das Nutzen-Risiko-Verhältnis zugunsten der Statine liegt. Will man der chronischen Neurodegeneration beim POWG wirkungsvoll entgegenwirken, ist der kombinierte Einsatz der verschiedenen Substanzen zum gegenwärtigen Wissensstand empfehlenswert.…”