Statins: mechanism, pharmacokinetics and muscle toxicity
How HMG-CoA reductase inhibition upregulates LDL receptors, the CTT rule of 22% fewer events per 1 mmol/L with a worked NNT, how lipophilicity and CYP3A4, OATP1B1 and SLCO1B1 shape interactions and myopathy, anti-HMGCR necrotising myopathy, and the nocebo trials.
Tier 2Medical sciences concept
Written with AI assistance and fact-checked against the sources below. For exam study, not clinical decisions. How notes are made
At a glance
- Statins competitively inhibit HMG-CoA reductase, the rate-limiting step of cholesterol synthesis. The fall in hepatocyte cholesterol upregulates LDL receptors, and that is how LDL falls.
- High-intensity statins (atorvastatin 40 to 80 mg, rosuvastatin 20 to 40 mg) lower LDL by about 50%.
- Each 1 mmol/L LDL reduction cuts major vascular events by about 22% (CTT).
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Sources
- Therapeutic Guidelines: CardiovascularAU/NZTherapeutic Guidelines Ltd, current eTG edition (version not verified)
- Australian guideline for assessing and managing cardiovascular disease riskAU/NZCommonwealth of Australia (Department of Health and Aged Care), 2023
- Cholesterol Treatment Trialists' Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010;376:1670-81Lancet, 2010
- Mach F, Koskinas KC, Roeters van Lennep JE et al. 2025 Focused Update of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J 2025;46(42):4359-4378European Society of Cardiology, 2025
- SEARCH Collaborative Group. SLCO1B1 variants and statin-induced myopathy: a genomewide study. N Engl J Med 2008;359:789-99N Engl J Med, 2008
- Wood FA, Howard JP, Finegold JA et al. N-of-1 trial of a statin, placebo, or no treatment to assess side effects (SAMSON). N Engl J Med 2020;383:2182-4N Engl J Med, 2020
- Cooper-DeHoff RM, Niemi M, Ramsey LB et al. The Clinical Pharmacogenetics Implementation Consortium guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and statin-associated musculoskeletal symptoms. Clin Pharmacol Ther 2022;111:1007-21Clin Pharmacol Ther, 2022
- Last updated
- 14 November 2026
What changed
- 14 November 2026 Personal emails, About story and Australian-style copy