Management of patients with statin intolerance

Fischer, Sabine; Julius, Ulrich

doi:10.1016/j.atherosclerosissup.2017.05.013

Cited by 11 publications

(3 citation statements)

References 21 publications

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“…In a recent review, it was suggested that in patients with statin intolerance, presenting muscle pain, treatment with another statin should be recommended (37). The most effective and tolerable statins that patients can be treated with are atorvastatin and rosuvastatin.…”

Section: Discussionmentioning

confidence: 99%

PCSK9 Antibody-based Treatment Strategies for Patients With Statin Intolerance

Voutyritsa

Damaskos

Farmaki

et al. 2021

In Vivo

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Section: Discussionmentioning

confidence: 99%

PCSK9 Antibody-based Treatment Strategies for Patients With Statin Intolerance

Voutyritsa

Damaskos

Farmaki

et al. 2021

In Vivo

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“…A recent study associated high doses of statins with an increased risk for osteoporosis [ 12 ]. The only available alternatives to statin monotherapy is combination therapy with either ezetimibe or inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) [ 13 , 14 ]. For example, combination therapy with ezetimibe and simvastatin was reported to reduce LDL cholesterol levels, to decrease adverse effects such as nonfatal myocardial infarction and stroke, and to lower the rates of cardiovascular death [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Lipid-Lowering Therapy during Cardiac Rehabilitation in Patients with Diabetes Mellitus and Coronary Heart Disease

Wittlinger

Schwaab

Völler

et al. 2021

JCDD

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Background: Cardiac rehabilitation (CR) in patients with coronary heart disease (CHD) increases adherence to a healthy lifestyle and to secondary preventive medication. A notable example of such medication is lipid-lowering therapy (LLT). LLT during CR improves quality of life and prognosis, and thus is particularly relevant for patients with diabetes mellitus, which is a major risk factor for CHD. Design: A prospective, multicenter registry study with patients from six rehabilitation centers in Germany. Methods: During CR, 1100 patients with a minimum age of 18 years and CHD documented by coronary angiography were included in a LLT registry. Results: In 369 patients (33.9%), diabetes mellitus was diagnosed. Diabetic patients were older (65.5 ± 9.0 vs. 62.2 ± 10.9 years, p < 0.001) than nondiabetic patients and were more likely to be obese (BMI: 30.2 ± 5.2 kg/m2 vs. 27.8 ± 4.2 kg/m2, p < 0.001). Analysis indicated that diabetic patients were more likely to show LDL cholesterol levels below 55 mg/dL than patients without diabetes at the start of CR (Odds Ratio (OR) 1.9; 95% CI 1.3 to 2.9) until 3 months of follow-up (OR 1.9; 95% CI 1.2 to 2.9). During 12 months of follow-up, overall and LDL cholesterol levels decreased within the first 3 months and remained at the lower level thereafter (p < 0.001), irrespective of prevalent diabetes. At the end of the follow-up period, LDL cholesterol did not differ significantly between patients with or without diabetes mellitus (p = 0.413). Conclusion: Within 3 months after CR, total and LDL cholesterol were significantly reduced, irrespective of prevalent diabetes mellitus. In addition, CHD patients with diabetes responded faster to LTT than nondiabetic patients, suggesting that diabetic patients benefit more from LLT treatment during CR.

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“…The circulating concentration of low-density lipoprotein (LDL) cholesterol is a well-established risk factor for cardiovascular disease [1, 2]. Although statins are currently the main treatment for hypercholesterolemia, many patients are statin intolerant [3–5] and inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) has recently emerged as an alternative or parallel approach to reduce cholesterol levels [6–9]. PCSK9 plays a key role in cholesterol homeostasis by directing membrane-bound LDL receptors to lysosomal degradation [10, 11].…”

Section: Introductionmentioning

confidence: 99%

In vivo genome and base editing of a human PCSK9 knock-in hypercholesterolemic mouse model

Carreras

Pane²,

Nitsch

et al. 2019

BMC Biol

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BackgroundPlasma concentration of low-density lipoprotein (LDL) cholesterol is a well-established risk factor for cardiovascular disease. Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9), which regulates cholesterol homeostasis, has recently emerged as an approach to reduce cholesterol levels. The development of humanized animal models is an important step to validate and study human drug targets, and use of genome and base editing has been proposed as a mean to target disease alleles.ResultsTo address the lack of validated models to test the safety and efficacy of techniques to target human PCSK9, we generated a liver-specific human PCSK9 knock-in mouse model (hPCSK9-KI). We showed that plasma concentrations of total cholesterol were higher in hPCSK9-KI than in wildtype mice and increased with age. Treatment with evolocumab, a monoclonal antibody that targets human PCSK9, reduced cholesterol levels in hPCSK9-KI but not in wildtype mice, showing that the hypercholesterolemic phenotype was driven by overexpression of human PCSK9. CRISPR-Cas9-mediated genome editing of human PCSK9 reduced plasma levels of human and not mouse PCSK9, and in parallel reduced plasma concentrations of total cholesterol; genome editing of mouse Pcsk9 did not reduce cholesterol levels. Base editing using a guide RNA that targeted human and mouse PCSK9 reduced plasma levels of human and mouse PCSK9 and total cholesterol. In our mouse model, base editing was more precise than genome editing, and no off-target editing nor chromosomal translocations were identified.ConclusionsHere, we describe a humanized mouse model with liver-specific expression of human PCSK9 and a human-like hypercholesterolemia phenotype, and demonstrate that this mouse can be used to evaluate antibody and gene editing-based (genome and base editing) therapies to modulate the expression of human PCSK9 and reduce cholesterol levels. We predict that this mouse model will be used in the future to understand the efficacy and safety of novel therapeutic approaches for hypercholesterolemia.Electronic supplementary materialThe online version of this article (10.1186/s12915-018-0624-2) contains supplementary material, which is available to authorized users.

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Management of patients with statin intolerance

Cited by 11 publications

References 21 publications

PCSK9 Antibody-based Treatment Strategies for Patients With Statin Intolerance

PCSK9 Antibody-based Treatment Strategies for Patients With Statin Intolerance

Efficacy of Lipid-Lowering Therapy during Cardiac Rehabilitation in Patients with Diabetes Mellitus and Coronary Heart Disease

In vivo genome and base editing of a human PCSK9 knock-in hypercholesterolemic mouse model

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