The Significance of Statin-Associated Muscle Symptoms and Its Impact on Patient Adherence and Outcomes

Abstract

S tatin-associated muscle symptoms (SAMS) are defined as a wide spectrum of muscle symptoms, including muscle aches, weakness, soreness, stiffness, cramping, tenderness, or general fatigue, associated with statin initiation. SAMS adverse events reports vary from blinded randomized control trials (1%-5%) to observational studies (7%-29%). 1,2 A recent metanalysis reported that during the first year, statin therapy produced a 7% relative increase in SAMS, also highlighting that only 1 of 15 SAMS adverse event patient reports were actually the result of the statin 3 . These may be also be due to the so-called nocebo effect. In fact, Gupta et l, 1 in a randomized, double-blind, placebo-controlled trial and its nonrandomized nonblind extension phase, described an increased rate of adverse events reports only when both patients and their doctors were aware of statin therapy use and not when they were blinded. Therefore, it is possible that there is adverse event overreporting. Because statins play a major role in cardiovascular disease prevention, it is crucial for physician to partner with the patient to gain a thorough symptom history and determine if he or she is truly statin intolerant. [2][3][4][5] SAMS usually involve both sides of large muscle groups (eg, buttocks, calves, shoulder girdle, thighs) and mostly develop between 4 and 6 weeks from statin initiation or increase. 6 Several risk factors have also emerged from several studies that may help to stratify patients at an increased risk of SAMS development, including medicine or food interactions (eg, CYP3A4A inhibitors), high-dose statin therapy, history of myopathy with other lipid-modifying medicines, regular vigorous physical activity, impaired hepatic or renal function, substance abuse (eg, alcohol, opioids, cocaine), female gender, and low body mass index. 6 However, further studies are needed to better clarify the association between risk factors and SAMS. In fact, Al-Makhamreh et al, 7 in their observational retrospective cohort study, did not confirm gender, and both kidney and hepatic impairment association with an increased risk of SAMS onset, giving more prominence instead to the presence of autoimmune diseases. Moreover, a recent metanalysis pointed out that statin therapy causes approximately 11 additional reports of any muscle pain or weakness per 1000 patients during the first year, with only a little increase thereafter, with some evidence of persistent risk for more intensive regimens. 3 A better detection and definition of SAMS has been addressed in the past as a crucial point to improve patient treatment adherence. 6 Moreover, in a systematic review, it was reported that 5%-15% of the patients ceased the medication due to adverse events onset. Of these, some patients complained that they were not properly informed about side effects before starting statin treatment. 8 Al-Makhamreh et al, 7 in their recent article, have reported a non-statistically significant difference between patients experiencing SAMS and the control group. This finding ...