Statin intolerance management: a systematic review

Meza-Contreras, Alejandra I; Wenczenovicz, Camila; Ruiz-Arellanos, Kim; Vesely, Elissa A Kinzelman; Mogollon, Renzo; Montori, Víctor M.

doi:10.1007/s12020-022-03263-w

Cited by 9 publications

(8 citation statements)

References 45 publications

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“…Preventative measures and early interventions focus on reducing systemic cholesterol-laden low-density lipoprotein (LDL) through lifestyle changes or medications 1, 2 . While cholesterol-lowering statins are one of the most prescribed drugs, many patients still require surgical intervention at later stages of disease 3, 4 , and cardiovascular diseases remain the leading cause of death in the world 5, 6 .…”

Section: Introductionmentioning

confidence: 99%

LDL-Binding IL-10 Reduces Vascular Inflammation in Atherosclerotic Mice

Volpatti,

de Matos,

Borjas

et al. 2024

Preprint

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Atherosclerosis is a chronic inflammatory disease associated with the accumulation of low-density lipoprotein (LDL) in arterial walls. Higher levels of the anti-inflammatory cytokine IL-10 in serum are correlated with reduced plaque burden. However, cytokine therapies have not translated well to the clinic, partially due to their rapid clearance and pleiotropic nature. Here, we engineered IL-10 to overcome these challenges by hitchhiking on LDL to atherosclerotic plaques. Specifically, we constructed fusion proteins in which one domain is IL-10 and the other is an antibody fragment (Fab) that binds to protein epitopes of LDL. In murine models of atherosclerosis, we show that systemically administered Fab-IL-10 constructs bind circulating LDL and traffic to atherosclerotic plaques. One such construct, 2D03-IL-10, significantly reduces aortic immune cell infiltration to levels comparable to healthy mice, whereas non-targeted IL-10 has no therapeutic effect. Mechanistically, we demonstrate that 2D03-IL-10 preferentially associates with foamy macrophages and reduces pro-inflammatory activation markers. This platform technology can be applied to a variety of therapeutics and shows promise as a potential targeted anti-inflammatory therapy in atherosclerosis.

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Section: Introductionmentioning

confidence: 99%

LDL-Binding IL-10 Reduces Vascular Inflammation in Atherosclerotic Mice

Volpatti,

de Matos,

Borjas

et al. 2024

Preprint

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“…Other factors like comorbidities (e.g. hypothyroidism, rheumatic polymyalgia, vitamin D deficiency), recent intense physical activity or trauma, viral infection, and polypharmacy have been shown to induce muscle pain and should be distinguished from the pain caused by statin use 12 , 15 , 17 – 19 . This distinction is especially important, because nonadherence to statin therapy puts a high burden on cardiovascular morbidity and mortality 11 .…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial complex III activity: from invasive muscle biopsies to patient-friendly buccal swab analysis

Somers

Allard²,

Siddiqi

et al. 2023

Sci Rep

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Drug-induced mitochondrial dysfunction is a common adverse effect, particularly in case of statins—the most prescribed drugs worldwide. These drugs have been shown to inhibit complex III (CIII) of the mitochondrial oxidative phosphorylation process, which is related to muscle pain. As muscle pain is the most common complaint of statin users, it is crucial to distinguish it from other causes of myalgia to prevent unnecessary cessation of drug therapy. However, diagnosing CIII inhibition currently requires muscle biopsies, which are invasive and not practical for routine testing. Less invasive alternatives for measurement of mitochondrial complex activities are only available yet for complex I and IV. Here, we describe a non-invasive spectrophotometric method to determine CIII catalytic activities using buccal swabs, which we validated in a cohort of statin and non-statin users. Our data indicate that CIII can be reliably measured in buccal swabs, as evidenced by reproducible results above the detection limit. Further validation on a large-scale clinical setting is recommended.

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“…These include older age, female sex, Asian or Black ethnicity, alcohol use, obesity, diabetes mellitus, hypothyroidism, chronic liver disease, kidney disease, and use of certain medications (e.g., antiarrhythmic agents or calcium channel blockers) [15]. Since the presentation of statin intolerance can mimic symptom presentation in other conditions such as vitamin D deficiency, polymyalgia rheumatica, poly myositis, hypothyroidism, and medication interactions, it is important to exclude these conditions before establishing the presence of statin intolerance [16]. Statin intolerance has also been reported as part of the spectrum in patients with multiple drug intolerances [17].…”

mentioning

confidence: 99%

“…Several strategies have been recommended to address statin intolerance and patient concerns related to intolerance. A systematic review by Meza-Contreras et al [16] identified 26 articles that described clinical strategies to address statin intolerance. Most of the studies recommended early exclusion of other causes of musculoskeletal symptoms such as vitamin D deficiency, polymyositis, hypothyroidism, or drug-drug interactions.…”

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confidence: 99%

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Overcoming patient reluctance to statin intolerance

Katamesh,

Mickow,

Huang

et al. 2024

Pol Heart J

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Statin therapy is a cornerstone in the management of dyslipidemia, both in primary and secondary prevention of cardiovascular events. Despite strong guidelines supporting statin use, concerns regarding side effects, particularly musculoskeletal symptoms, contribute to statin intolerance and patient reluctance. While statin intolerance is reported in 5% to 30% of patients, its true prevalence may be overestimated due to the influence of the nocebo effect. Factors associated with higher incidence of statin intolerance include older age, female sex, comorbidities such as diabetes and chronic kidney disease, and concurrent use of medications such as antiarrhythmic agents or calcium channel blockers. Clinical characterization of statin intolerance requires thorough evaluation and exclusion of alternative causes of musculoskeletal symptoms. Strategies to address statin intolerance include reassessing cardiovascular risk, engaging in shared decision-making, statin rechallenge after appropriate washout periods, dosage titration for tolerability, and consideration of alternative therapies when low-density lipoprotein goals cannot be achieved with statins. This review provides an overview of the spectrum of statin intolerance, its clinical assessment, and a systematic approach to caring for a patient with statin intolerance.

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Statin intolerance management: a systematic review

Cited by 9 publications

References 45 publications

LDL-Binding IL-10 Reduces Vascular Inflammation in Atherosclerotic Mice

LDL-Binding IL-10 Reduces Vascular Inflammation in Atherosclerotic Mice

Mitochondrial complex III activity: from invasive muscle biopsies to patient-friendly buccal swab analysis

Overcoming patient reluctance to statin intolerance

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