{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T15:45:28Z","timestamp":1786808728609,"version":"build-2736575974"},"reference-count":23,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide, and lowering low-density lipoprotein cholesterol (LDL-C) remains a cornerstone of cardiovascular prevention. Statins are among the most extensively studied and widely prescribed medications and have demonstrated substantial benefits in reducing major adverse cardiovascular events in both primary and secondary prevention settings. Nevertheless, the effectiveness of statin therapy in routine clinical practice is frequently compromised by poor adherence, treatment discontinuation, concerns regarding adverse effects, and persistent residual cardiovascular risk. This narrative review synthesises contemporary evidence relating to the mechanisms of action of statins, their role in primary and secondary prevention, determinants of medication adherence, statin-associated muscle symptoms (SAMSs), and emerging developments in precision cardiovascular medicine. Current evidence indicates that although statins remain highly effective in reducing cardiovascular risk, long-term treatment success is strongly influenced by behavioural, psychological, social, and healthcare system factors. Increasing attention has also been directed towards the multifactorial nature of SAMSs and the contribution of nocebo effects to perceived statin intolerance. Emerging approaches involving pharmacogenomics, artificial intelligence, digital health technologies, and multidimensional risk assessment offer opportunities for more individualised prevention strategies, although important limitations relating to cost, accessibility, and external validity remain. Overall, contemporary cardiovascular prevention requires a patient-centred approach that integrates biological, behavioural, and social determinants of health to optimise treatment adherence and improve long-term cardiovascular outcomes.<\/jats:p>","DOI":"10.3390\/ijerph23070921","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T12:00:17Z","timestamp":1784548817000},"page":"921","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Statin Therapy and Cardiovascular Prevention: Contemporary Evidence, Challenges, and Future Directions\u2014A Narrative Review"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1993-9793","authenticated-orcid":false,"given":"Don","family":"Zachariah","sequence":"first","affiliation":[{"name":"Faculty of Health Sciences, North West University, Potchefstroom 2520, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic","family":"Kakooza","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, North West University, Potchefstroom 2520, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharifa","family":"Pothas","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, North West University, Potchefstroom 2520, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjana","family":"Thomas","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, North West University, Potchefstroom 2520, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8636-7174","authenticated-orcid":false,"given":"Lanthe","family":"Kruger","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, North West University, Potchefstroom 2520, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1093\/eurheartj\/ehz455","article-title":"2019 ESC\/EAS Guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk","volume":"41","author":"Mach","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e254","DOI":"10.1161\/CIR.0000000000000950","article-title":"Heart disease and stroke statistics\u20142021 update: A report from the American Heart Association","volume":"143","author":"Virani","year":"2021","journal-title":"Circulation"},{"key":"ref_3","unstructured":"Cholesterol Treatment Trialists\u2019 Collaboration (2019). Cholesterol Treatment Trialists\u2019 (CTT) Collaboration. Efficacy and safety of statin therapy in older people: A meta-analysis of individual participant data from 28 randomised controlled trials. Lancet, 393, 407\u2013415."},{"key":"ref_4","first-page":"e1082","article-title":"2018 AHA\/ACC\/AACVPR\/AAPA\/ABC\/ACPM\/ADA\/AGS\/APhA\/ASPC\/NLA\/PCNA guideline on the management of blood cholesterol","volume":"139","author":"Grundy","year":"2019","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Costa, D., Ielapi, N., Bevacqua, E., Ciranni, S., Cristodoro, L., Torcia, G., and Serra, R. (2023). Social determinants of health and vascular diseases: A systematic review and call for action. Soc. Sci., 12.","DOI":"10.3390\/socsci12040214"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.1093\/eurheartj\/ehx144","article-title":"Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies","volume":"38","author":"Ference","year":"2017","journal-title":"Eur. Heart J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/s41586-021-03392-8","article-title":"The changing landscape of atherosclerosis","volume":"592","author":"Libby","year":"2021","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3227","DOI":"10.1093\/eurheartj\/ehab484","article-title":"2021 ESC Guidelines on cardiovascular disease prevention in clinical practice","volume":"42","author":"Visseren","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1056\/NEJMoa1615664","article-title":"Evolocumab and clinical outcomes in patients with cardiovascular disease","volume":"376","author":"Sabatine","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2940","DOI":"10.1093\/eurheartj\/eht295","article-title":"Adherence to cardiovascular therapy: A meta-analysis of prevalence and clinical consequences","volume":"34","author":"Chowdhury","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Horne, R., Chapman, S.C.E., Parham, R., Freemantle, N., Forbes, A., and Cooper, V. (2013). Understanding patients\u2019 adherence-related beliefs about medicines prescribed for long-term conditions: A meta-analytic review of the Necessity-Concerns Framework. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0080633"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2182","DOI":"10.1056\/NEJMc2031173","article-title":"N-of-1 trial of a statin, placebo, or no treatment to assess side effects","volume":"383","author":"Wood","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1136\/bmj.n135","article-title":"Statin treatment and muscle symptoms: Series of randomised, placebo controlled n-of-1 trials","volume":"372","author":"Herrett","year":"2021","journal-title":"BMJ"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.jacl.2022.05.068","article-title":"National Lipid Association scientific statement on statin intolerance: A new definition and key considerations for ASCVD risk reduction in the statin intolerant patient","volume":"16","author":"Cheeley","year":"2022","journal-title":"J. Clin. Lipidol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1093\/eurheartj\/ehr224","article-title":"Opposite effects of statins on mitochondria of cardiac and skeletal muscles: A \u201cmitohormesis\u201d mechanism involving reactive oxygen species and PGC-1","volume":"33","author":"Bouitbir","year":"2012","journal-title":"Eur. Heart J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1016\/j.jacc.2021.07.022","article-title":"Side effect patterns in a crossover trial of statin, placebo, and no treatment","volume":"78","author":"Howard","year":"2021","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2387","DOI":"10.1056\/NEJMoa1410489","article-title":"Ezetimibe added to statin therapy after acute coronary syndromes","volume":"372","author":"Cannon","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1056\/NEJMoa1801174","article-title":"Alirocumab and cardiovascular outcomes after acute coronary syndrome","volume":"379","author":"Schwartz","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1056\/NEJMoa2215024","article-title":"Bempedoic acid and cardiovascular outcomes in statin-intolerant patients","volume":"388","author":"Nissen","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.2147\/CIA.S194543","article-title":"Grip strength: An indispensable biomarker for older adults","volume":"14","author":"Bohannon","year":"2019","journal-title":"Clin. Interv. Aging"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1038\/s41430-022-01131-4","article-title":"Phase angle of bioimpedance at 50 kHz is associated with cardiovascular diseases: Systematic review and meta-analysis","volume":"76","author":"Ceolin","year":"2022","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e615","DOI":"10.1016\/S2589-7500(22)00111-X","article-title":"Effectiveness of wearable activity trackers to increase physical activity and improve health: A systematic review of systematic reviews and meta-analyses","volume":"4","author":"Ferguson","year":"2022","journal-title":"Lancet Digit. Health"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e18694","DOI":"10.2196\/18694","article-title":"Reliability and validity of commercially available wearable devices for measuring steps, energy expenditure, and heart rate: Systematic review","volume":"8","author":"Fuller","year":"2020","journal-title":"JMIR mHealth uHealth"}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/23\/7\/921\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T04:38:31Z","timestamp":1784608711000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/23\/7\/921"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,17]]},"references-count":23,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijerph23070921"],"URL":"https:\/\/doi.org\/10.3390\/ijerph23070921","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,17]]}}}