Discussion around statin discontinuation in older adults and patients with wasting diseases
Open accessAbstract
Statins are usually selected as the first-line therapy to lower plasma levels of low-density lipoprotein cholesterol (LDL-C) and cardiovascular disease (CVD) morbidity and mortality.1 They reduce the risk of myocardial infarction, stroke and CVD mortality by about 25–30%.2 That is one of the reasons why all current clinical guidelines 'virtually mandate' lifetime use of statins once they are started, thus becoming a challenge for the patients due to their possible side effects.3 Furthermore, there has been recently a tendency towards maximizing the strength of statin treatment, sometimes with greater doses or potent forms.3, 4 The IMProved Reduction of Outcomes: Vytorin Efficacy International Trial showed that the combination with ezetimibe/simvastatin 10 mg/40 mg let to an absolute 2.0% reduction (relative risk reduction: 6.4%) of the risk of CV events in contrast to simvastatin 40 mg alone.4, 5 The trial also demonstrated that the patients with obtained very low LDL-C levels <30 mg/dL experienced no discrepancies in adverse effects than those with higher LDL-C levels.5 ODYSSEY LONG-TERM and the Open-Label Study of Long-term Evaluation against LDL-C trials with proprotein convertase subtilisin/kexin type 9 inhibitors also supported the hypothesis 'the lower the better' for LDL-C levels, generating more arguments for lower LDL-C targets <50 mg/dL (1.3 mmol/L), in contrast with the current targets <70 mg/dL (1.8 mmol/L) for patients at the highest risk.6 These results are in line with the 2013 American College of Cardiology/American Heart Association guidelines, which advise the use of high-intensity statin therapy and extend its use to more categories susceptible to CVD.7 Taking into account still poor to moderate statin therapy control in the high-risk and highest-risk patients (even 50% of patients are non-adherent to therapy after 2 years), as well as the aforementioned data, more intense targets seem to be very important; however, on the other hand, high-intensity statin therapy might also increase the risk of statin-related side effects and statin discontinuation rate due to this fact.6 Statin discontinuation may concern the patients with complete statin intolerance,8 as well as patients with cancer, palliative care patients, patients with cachexia,9 but also elderly patients, and primary CV prevention individuals, in which the risk of statin-related side effects (mainly associated with new-onset diabetes) might exceed the benefits (especially with subjects with risk factors of diabetes well adhered to non-pharmacological therapy).10 Statin discontinuation (as well as essential dose reduction) has been associated with higher risk for CVD events and death in patients with coronary artery disease (CAD), and especially in patients after acute coronary syndrome, in which the instability of atheroma plaque might appear.3, 11 However, research on the causes of discontinuation of statins in routine practice is still very limited.3, 8 In the retrospective cohort study, the authors investigated the reasons for statin discontinuation and the role of statin-related side effects in 134 263 statin users from the Brigham and Women's Hospital and Massachusetts General Hospital.12 Of these, 53.1% patients reported statin discontinuation at least once, and 17.4% reported statin-related events. More than half of the patients who stopped taking a statin because of a statin-related event were successfully restarted with a statin.12 Another survey, conducted in the group of 1074 French subjects treated with low doses of rosuvastatin, atorvastatin or simvastatin, reported statin discontinuation in 30% of the symptomatic patients due to muscular symptoms.13 Approximately 38% of them reported that their symptoms prevented even moderate exertion during everyday activities, while 42% of patients suffered major disruption to their everyday life.13 In the Understanding Statin Use in America and Gaps in Education survey carried out on 10 138 US adults, the causes of discontinuation were muscle side effects (60%), cost (16%) and perceived lack of efficacy (13%).14 However, in randomized placebo-controlled trials (RCTs), it has been shown that statins do not increase minor or serious symptomatic adverse events.15 A meta-analysis involving more than 80 000 patients from 29 RCTs found that only a small minority of side effects was attributable to statins.16 On the other hand, the misinterpretation of trial facts about statin side effects might cause harm to patients,17 and it needs to be emphasized that most patients with any side effects to statin therapy as well as statin therapy non-adherence were excluded from RCTs at baseline.6 Data so far also support the possibility of unnecessary statin discontinuation in patients who like to report side effects (so-called nocebo effect), thereby placing them at increased risk of CVD.18 Statins have an acceptable margin of safety, when used in properly selected individuals who are appropriatel
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Statin intolerance limits effective treatment of patients at risk of atherosclerotic cardiovascular disease and is the main cause of statin nonadherence and discontinuation.
“In clinical practice, statin intolerance limits the effective treatment of patients at risk of atherosclerotic cardiovascular disease (CVD), and represents the main cause of statin nonadherence and discontinuation (11,12).”
From The Role of Nutraceuticals in Statin Intolerant Patients (2018) · cites this paper as [12]
For most patients with statin-associated muscle symptoms, even up to 95%, statins can still be used with a step-by-step approach, because complete statin intolerance affects only 3% to 5% of patients.
“Moreover, for most (even 95%) of the patients with SAMS, it is still possible to use statins using a step-bystep approach, as complete statin intolerance affects only 3% to 5% patients (10)(11)(12).”
From The Role of Nutraceuticals in Statin Intolerant Patients (2018) · cites this paper as [12]
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“6 Data so far also support the possibility of unnecessary statin discontinuation in patients who like to report side effects (so-called nocebo effect ), thereby placing them at increased risk of CVD. 18 Statins have an acceptable margin of safety, when used in properly selected individuals who are appropriately monito…”
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“Another group of patients who might benefit from such nutraceuticals consists of very old patients (especially those aged over 75) or patients with sarcopenia [40].”
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An analysis of the types of recently published research in the field of cachexia
Shewan, L. G. (2017) · European Journal of Preventive Cardiology · doi:10.1177/2047487317730943 · Cited by 5 · see citing works
Hale, M. D., Zaman, H., Mehdizadeh, D., Todd, O. M., Callaghan, H., Gale, C. P., & Clegg, A. P. (2020) · Drugs & Aging · doi:10.1007/s40266-020-00798-3 · Cited by 5 · see citing works
Association Between Reduced Handgrip Strength and Commonly Prescribed MedicationsPreprint
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Time to jump on the bandwagon: the Journal of Cachexia, Sarcopenia and Muscle in 2018
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Cao, W., Li, L., Mathur, P., Thompson, J., & Milks, M. W. (2023) · BMC Medical Informatics and Decision Making · doi:10.1186/s12911-023-02221-4 · Cited by 3 · see citing works
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Management of Statin Intolerance
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Does coenzyme Q10 play a role in the risk of new-onset diabetes due to statins?
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“And the anxiety of new-onset diabetes can cause poor adherence to statin therapy, which can also weaken the benefit of statin therapy [7,8].”
BackgroundStatins in real clinical practice: current guidelines, possibilities of new schemes for their use
Sargsyan, V. D., Kamyshova, T. V., Safaryan, A. S., Ахмеджанов, Н. М., Небиеридзе, Д. В., & Александровна, П. Е. (2019) · Russian Journal of Preventive Medicine · doi:10.17116/profmed20192203186 · Cited by 1 · see citing works
Manejo de la intolerancia a estatinas: un desafío cotidiano en la práctica clínica
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“A pesar de la sólida evidencia científica sobre los beneficios de las estatinas, la tasa de discontinuación continúa siendo elevada, próxima a 50% luego de un año del evento, aun en pacientes con enfermedad cardiovascular (ECV) ateromatosa establecida(5).”
BackgroundVanajakshamma, V., Kasala, L., & Chanda, N. (2019) · Indian Journal of Cardiovascular Disease in Women · doi:10.1055/s-0039-1697076
Mechanisms of statin effects on muscle and neuronal proteostasis
Yu, D. (2020) · OpenCommons - UConn (University of Connecticut)
Bempedoic Acid: A First-in-Class Agent for Lowering Cholesterol Levels
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“6 Despite the availability of newer therapies and the higher risk of statin intolerance in the older adults, 33,34 non-statin therapies were used by only 2.1% of patients.”
BackgroundInfluentialDislipidemia en personas de edad muy avanzada
Friocourt, P. (2024) · EMC - Tratado de Medicina · doi:10.1016/s1636-5410(24)49306-9
Dislipidemie del grande anziano
Friocourt, P. (2024) · EMC - AKOS - Trattato di Medicina · doi:10.1016/s1634-7358(24)49439-4
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Awad, K., Mohammed, M., Zaki, M. M., Abushouk, A. I., Lip, G. Y. H., Blaha, M. J., Lavie, C. J., Toth, P. P., Jukema, J. W., Sattar, N. A., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14821102
Awad, K., Mohammed, M., Zaki, M. M., Abushouk, A. I., Lip, G. Y. H., Blaha, M. J., Lavie, C. J., Toth, P. P., Jukema, J. W., Sattar, N. A., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14821093
Awad, K., Mohammed, M., Zaki, M. M., Abushouk, A. I., Lip, G. Y. H., Blaha, M. J., Lavie, C. J., Toth, P. P., Jukema, J. W., Sattar, N. A., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14821099
Awad, K., Mohammed, M., Zaki, M. M., Abushouk, A. I., Lip, G. Y. H., Blaha, M. J., Lavie, C. J., Toth, P. P., Jukema, J. W., Sattar, N. A., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14821105
Awad, K., Mohammed, M., Zaki, M. M., Abushouk, A. I., Lip, G. Y. H., Blaha, M. J., Lavie, C. J., Toth, P. P., Jukema, J. W., Sattar, N. A., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14821084
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Awad, K., Mohammed, M., Zaki, M. M., Abushouk, A. I., Lip, G. Y. H., Blaha, M. J., Lavie, C. J., Toth, P. P., Jukema, J. W., Sattar, N. A., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14821081
Dyslipidémies de la personne très âgée
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- Authors
- Banach, M., & Serban, M.
- Affiliations
- Medical University of Lodz (PL)
- Department of Epidemiology University of Alabama at Birmingham Birmingham AL USA
- Corresponding author
- Banach, Maciej
- ORCID
- Banach, Maciej
- Venue
- Journal of Cachexia Sarcopenia and Muscle
- Publisher
- Wiley
- Published
- 2016-02-29
- Volume
- 7
- Issue
- 4
- Pages
- 396-399
- ISSN
- 2190-5991 (ISSN-L)
- 2190-6009
- PMC
- PMC4782254
- OpenAlex
- W2334642185
- Cited by
- 56
- References
- 33
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 13 · 2020: 4 · 2019: 7 · 2018: 8 · 2017: 10 · 2016: 4 · 2013: 1
- FWCI
- 10.70
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Cachexia Sarcopenia and Muscle (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
- Keywords
- statin intolerance, older adults, wasting disease, cachexia, cancer, palliative care, high-intensity statin therapy, statin adverse effects, cardiovascular disease prevention, lipid-lowering therapy, ezetimibe/simvastatin, PCSK9 inhibitors, medication adherence, primary prevention of cardiovascular disease, secondary prevention
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