Diagnosis and Management of Statin Intolerance

Alonso, Rodrigo; Cuevas, Ada; Cafferata, Alberto

doi:10.5551/jat.rv17030

Cited by 74 publications

(63 citation statements)

References 62 publications

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“…We have also encountered patients whose statinassociated muscle symptoms appeared to respond to supplements of coenzyme Q10, some of which were self-initiated. We agree with Alonso et al 1) that the current evidence from a meta-analysis of randomized controlled trials does not support the use of coenzyme Q10 for statin-related symptoms, and anecdotal case reports do not provide high-quality supportive evidence. Nevertheless, we would suggest that it is worth conducting a trial of coenzyme Q10 in some patients with apparent statin intolerance as it is essential for patients to continue statin therapy when it is truly indicated.…”

Section: To the Editorsupporting

confidence: 74%

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Statin Intolerance—An Asian Perspective

Tomlinson

Chan

Liu

2020

JAT

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Section: To the Editorsupporting

confidence: 74%

“…The recent article in this journal by Alonso and colleagues provides a helpful review of the diagnosis and management of statin intolerance 1) . The authors listed the major risk factors for statin-associated muscle symptoms; however, they did not include Asian ethnicity in the list.…”

Section: To the Editormentioning

confidence: 99%

Statin Intolerance—An Asian Perspective

Tomlinson

Chan

Liu

2020

JAT

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“…The benefits and risks of continuing, temporarily suspending, and discontinuing statin treatment need to be weighed up. Additional patient counselling involves discussion about the nocebo effect and complimentary therapeutic lifestyle changes (e.g., smoking cessation, blood pressure control, adopting the Mediterranean diet) [67,266]. There is no gold-standard diagnostic method nor a validated questionnaire for SRM, although a myalgia clinical index score has been proposed by the NLA [267].…”

Section: Management Of Srmmentioning

confidence: 99%

Statin-Related Myotoxicity: A Comprehensive Review of Pharmacokinetic, Pharmacogenomic and Muscle Components

Turner

Pirmohamed

2019

JCM

141

126

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Statins are a cornerstone in the pharmacological prevention of cardiovascular disease. Although generally well tolerated, a small subset of patients experience statin-related myotoxicity (SRM). SRM is heterogeneous in presentation; phenotypes include the relatively more common myalgias, infrequent myopathies, and rare rhabdomyolysis. Very rarely, statins induce an anti-HMGCR positive immune-mediated necrotizing myopathy. Diagnosing SRM in clinical practice can be challenging, particularly for mild SRM that is frequently due to alternative aetiologies and the nocebo effect. Nevertheless, SRM can directly harm patients and lead to statin discontinuation/non-adherence, which increases the risk of cardiovascular events. Several factors increase systemic statin exposure and predispose to SRM, including advanced age, concomitant medications, and the nonsynonymous variant, rs4149056, in SLCO1B1, which encodes the hepatic sinusoidal transporter, OATP1B1. Increased exposure of skeletal muscle to statins increases the risk of mitochondrial dysfunction, calcium signalling disruption, reduced prenylation, atrogin-1 mediated atrophy and pro-apoptotic signalling. Rare variants in several metabolic myopathy genes including CACNA1S, CPT2, LPIN1, PYGM and RYR1 increase myopathy/rhabdomyolysis risk following statin exposure. The immune system is implicated in both conventional statin intolerance/myotoxicity via LILRB5 rs12975366, and a strong association exists between HLA-DRB1*11:01 and anti-HMGCR positive myopathy. Epigenetic factors (miR-499-5p, miR-145) have also been implicated in statin myotoxicity. SRM remains a challenge to the safe and effective use of statins, although consensus strategies to manage SRM have been proposed. Further research is required, including stringent phenotyping of mild SRM through N-of-1 trials coupled to systems pharmacology omics- approaches to identify novel risk factors and provide mechanistic insight.

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“…3 Similarly, observational studies have shown that a substantial proportion of patients cannot or do not take statins as prescribed due to intolerance, non-adherence, or barriers to accessing medication, with adherence rates ranging from 25% to 60% in different clinical settings. 4 Although many definitions of statin intolerance have been proposed, 5,6 a pragmatic operational definition may be the inability to tolerate statin treatment, usually due to the occurrence of symptoms and/ or laboratory abnormalities.…”

Section: Introductionmentioning

confidence: 99%

Intensity of statin treatment after acute coronary syndrome, residual risk, and its modification by alirocumab: insights from the ODYSSEY OUTCOMES trial

Dı́az

Bhatt

et al. 2020

European Journal of Preventive Cardiology

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Aims Statins are pivotal to the secondary prevention of major adverse cardiovascular events, but some patients are statin-intolerant. We examined the effects of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab on the risk of major adverse cardiovascular events according to the intensity of background statin treatment. Methods and results The ODYSSEY OUTCOMES trial compared alirocumab with placebo in 18,924 patients with acute coronary syndrome and dyslipidaemia despite intensive or maximum-tolerated statin treatment (including no statin if intolerance was documented). The primary outcome (major adverse cardiovascular events) comprised coronary heart disease death, non-fatal myocardial infarction, ischaemic stroke, or unstable angina. Median follow-up was 2.8 years. Baseline statin treatment was high-intensity (88.8%), low/moderate-intensity (8.7%) or none (2.4%). Median baseline low-density lipoprotein cholesterol was 86, 89 and 139 mg/dL ( P < 0.001) in these statin treatment categories, respectively. Alirocumab produced similar relative reductions in low-density lipoprotein cholesterol from baseline across statin treatment subgroups, but the mean absolute reductions differed (52.9, 56.7 and 86.1 mg/dL, respectively; P < 0.001). With placebo, the incidence of major adverse cardiovascular events was highest in the no statin subgroup (10.8%, 10.7% and 26.0% respectively). Alirocumab reduced major adverse cardiovascular events in each statin subgroup (hazard ratio 0.88, 95% confidence interval (CI) 0.80–0.96; 0.68, 0.49–0.94; and 0.65, 0.44–0.97, respectively; Pinteraction = 0.14) with a gradient of absolute risk reduction: 1.25%, 95% CI 0.34–2.16; 3.16%, 0.38–5.94; 7.97%, 0.42–15.51; Pinteraction = 0.106). Conclusions PCSK9 inhibition with alirocumab reduces the relative risk of major adverse cardiovascular events after acute coronary syndrome irrespective of background statin treatment. However, patients on no statin are at high absolute risk for recurrent major adverse cardiovascular events; alirocumab substantially reduces that risk. PCSK9 inhibition may be an important therapeutic strategy for statin-intolerant patients with acute coronary syndrome.

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Diagnosis and Management of Statin Intolerance

Cited by 74 publications

References 62 publications

Statin Intolerance—An Asian Perspective

Statin Intolerance—An Asian Perspective

Statin-Related Myotoxicity: A Comprehensive Review of Pharmacokinetic, Pharmacogenomic and Muscle Components

Intensity of statin treatment after acute coronary syndrome, residual risk, and its modification by alirocumab: insights from the ODYSSEY OUTCOMES trial

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