UNASSIGNED: The prevalence of carotid artery stenosis in the general population is approximately 3%, but approximately 20% among people with acute ischemic stroke. Statins are recommended by multiple international guidelines as the drug of choice for lipid control in people with asymptomatic or symptomatic carotid artery stenosis due to their lipid-lowering and other pleiotropic effects.
UNASSIGNED: This review discusses the guidelines for statin usage as a cornerstone in the prevention and management of atherosclerotic carotid artery disease and the impact of statins on stroke incidence and mortality. Statin side effects, alternative therapy, and genetic polymorphisms are reviewed.
UNASSIGNED: Statin therapy is associated with a decreased incidence of stroke and mortality as well as improved outcomes for patients treated with carotid revascularization. Statins are a safe and effective class of medications, but the initiation of therapy warrants close monitoring to avoid rare and potentially serious side effects. Lack of clinical efficacy or the presence of side effects suggests a need for treatment with an alternative therapy such as PCSK9 inhibitors. Understanding the interplay between the mechanisms of statins and PCSK9 inhibition therapies will allow optimal benefits while minimizing risks. Future research into genetic polymorphisms may improve patient selection for personalized therapy.

The efficacy of statins in the primary and secondary prevention of cardiovascular disease has been proven beyond doubt. The number needed to treat to prevent one cardiovascular event is 1 in 30 over 10 years, and the number needed to treat for secondary prevention is much lower. However, a recent study demonstrated that only 68% of eligible patients are on statin therapy. Moreover, there seems to be a reluctance to escalate statin doses due to the fear of adverse effects. The adverse effects that worries patients and their physicians most frequently are those related to muscular symptoms. N-of-1 trial evidence suggests that muscular symptoms attributed to statins are often caused by the nocebo effect. This article aims to provide a structured, evidence-based approach to suspected statin-related muscle toxicity.

To provide a systematic approach to management of the patient with statin-attributed muscle symptoms.
We examined the prevalence of statin intolerance, the role of the nocebo effect, key findings in the patient\'s history and laboratory studies, the potential value of coronary calcium scoring, and the importance of shared decision-making in considering statin re-initiation. Most patients with statin-attributed muscle symptoms can be successfully treated with statins or a combination of statins and non-statins to achieve successful ASCVD risk reduction.

BACKGROUND: Although low vitamin D levels are associated with statin-associated muscle symptoms (SAMS), it remains unclear if vitamin D supplementation leads to symptom improvement.
OBJECTIVE: We performed a systematic review to evaluate the association of vitamin D supplementation with resolution of SAMS.
METHODS: We searched Medline (PubMed), Embase and Cochrane Library till 12 December 2021. Full length articles that reported on the association between vitamin D supplementation in adult patients with SAMS were included.
RESULTS: We identified 8 interventional studies comprising 669 participants. Majority of the participants were of Caucasian ethnicity and the mean age of participants ranged from 59.5 to 64.8 years old. The studies recruited patients with initial mean pre-treatment vitamin D levels ranging from 17.8 to 22.0ng/mL. Follow up duration ranged from 2 to 24 months and mean post-treatment vitamin D levels ranged from 34.3 to 56.0ng/mL. We found that vitamin D supplementation was associated with improved statin tolerance in 509 out of 606 (83.9%) patients across the 7 studies which reported patient numbers after supplementation (95% CI = 0.81-0.87, I2 = 72% n = 7). None of the studies were randomized controlled trials (RCTs) and hence placebo effect of vitamin D could not be ruled out. Nocebo effect of statin was also not assessed by any of the studies.
CONCLUSIONS: Vitamin D supplementation in patients with mild-moderate vitamin D insufficiency was associated with improvement of SAMS. However, quantitative efficacy analysis was not possible and this observed association is likely confounded by nocebo and placebo effects. RCTs are required to conclusively assess the utility of vitamin D supplementation in improving SAMS.

Addressing the factors which lead to the development of statin-associated muscle symptoms (SAMS) is vital for maintaining patient compliance with these pharmaceuticals, and thus improving patient outcomes. This study aimed to clarify the relationship between statin lipophilicity, or dose, and the frequency of adverse muscle symptoms using a systematic review of randomised controlled trials (RCTs). RCTs, including statin monotherapy and placebo groups, which reported data on muscle adverse events were identified through the PubMed and Scopus databases. Risk ratios (RRs) and 95% confidence intervals (CI) were pooled using a random-effects meta-analysis. A total of 135 RCTs were included in this review. Statin therapy was associated with a significant, but modest, increase in the risk of adverse muscle symptoms compared to placebo (RR=1.050; 95% CI=1.014-1.089; P=0.007; I2=3.291%). This significant association was primarily due to the inclusion of RCTs recruiting participants with a history of statin intolerance. Lipophilic statins had no appreciable impact on the development of SAMS compared to hydrophilic formulations. A univariate meta-regression of dose (standardised to atorvastatin dose equivalents) and the risk of musculoskeletal complaints also showed no significant association. The results obtained from this meta-analysis indicate that there is a slight increase in the risk of SAMS, especially in individuals with a history of statin intolerance. There is limited evidence to suggest that the risk of SAMS would differ between the use of lipophilic and hydrophilic statins, or high- and low-dose therapy.