Statin-Induced Myopathy: The Two Faces of Janus

Abstract

Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have been shown to be effective at lowering low-density lipoprotein cholesterol and decreasing the risk of coronary heart disease. Although safe and well tolerated by most patients, statins have also been associated with muscle-related adverse events. This article reviews statin-associated myotoxicity to clarify the definitions of muscle-related adverse events and discusses their incidences in major statin trials, case reports, and review articles through January 2006. Milder complaints (ie, myalgia) are reported by approximately 5% to 7% of patients who take statins. More severe myotoxicity, namely rhabdomyolysis, is extremely rare for all statins save cerivastatin, and most recent estimates of its incidence are between 0.44 and 0.54 cases per 10 000 person-years. The mechanism of statin-associated myotoxicity has not been satisfactorily defined and is likely due to multiple factors, including membrane instability, mitochondrial dysfunction, and defects in myocyte duplication.

Inhibition of Rab1 GTPase and Endoplasmic Reticulum-to-Golgi Trafficking Underlies Statin's Toxicity in Rat Skeletal Myofibers

“…However, statins have adverse effects on skeletal muscles, ranging from slight myalgia to severe rhabdomyolysis (Arora et al, 2006). Among skeletal muscles, statins selectively injure fast-twitch glycolytic type II skeletal muscles (Waclawik et al, 1993;Westwood et al, 2005).…”

Myopathy as a Side Effect of Statin Therapy: Mechanisms of Development and Prospects for Treatment

“…Существуют исследования, в которых описаны несколько пациен-тов с рабдомиолизом, индуцированным статинами, изначально имеющих метаболические дефекты мио-цитов, что указывает на клиническое проявление асимптоматических метаболических миопатий на фоне приёма статинов [7,17].…”

“…Предполагается, что статины вызывают митохондриальную дисфункцию, нестабильность мембран, нарушают экспрессию генов, отвечающих за апоптоз (происходит индукция апоптоза миоцитов) и деградацию белка [7,8,10,12,13].…”

“…Согласно данным ран-домизированных контролируемых исследований жа-лобы на миалгию предъявляют приблизительно 5-7% пациентов, принимающих статины. Рабдомиолиз, к счастью, развивается чрезвычайно редко -частота его возникновения колеблется от 0,44 до 0,54 случаев на 10000 человек в год [7].…”

Drug-induced disorders of the nervous system

“…The incidence of statin-induced neuropathy is approximately 0.3 per 10,000 patient-years. 8 It can present up to two years after starting treatment. Clinical features include distal lower limb dysaesthesia and anaesthesia, proximal and distal weakness, and fasciculations.…”