Atorvastatin
| Evidence Level: L1 | Predicted Indications: 10 |
Table of Contents
- Atorvastatin
- Atorvastatin: From Hyperlipidaemia and Atherosclerotic Disease to Familial Hypercholesterolemia
Atorvastatin: From Hyperlipidaemia and Atherosclerotic Disease to Familial Hypercholesterolemia
One-Sentence Summary
Atorvastatin is a statin originally used to lower blood lipids and to prevent stroke and atherosclerotic disease. The TxGNN model predicts it may be effective for familial hypercholesterolemia, a prediction that is largely on-label or label-adjacent rather than true repurposing, with 13 clinical trials and 18 publications compiled for this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Hypertriglyceridemia, stroke and cerebrovascular disorders, atherosclerosis, familial combined hyperlipidemia, hyperlipoproteinemia, homozygous familial hypercholesterolemia (derived from the knowledge graph; the Singapore licences carry no indication text) |
| Predicted New Indication | Familial hypercholesterolemia |
| TxGNN Prediction Score | 99.42% |
| Evidence Level | L1 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 20 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on established pharmacology, atorvastatin inhibits HMG-CoA reductase, the key enzyme of cholesterol synthesis. This increases hepatic LDL receptor expression and speeds LDL cholesterol clearance.
Familial hypercholesterolemia is a genetic condition of impaired LDL clearance, and atorvastatin's known indications already include homozygous familial hypercholesterolemia. Its use in heterozygous disease is therefore a close extension of existing use, not a new therapeutic concept. Because the mechanism acts on the same LDL-clearance pathway, the prediction is biologically plausible.
Other predictions in this analysis are far weaker. Autosomal dominant hypercholesterolemia (rank 8) is essentially the same condition and is also supported. HIV infection (rank 2) has small, mixed studies and is better framed as HIV-associated dyslipidaemia or cardiovascular risk. The remaining predictions (brain stem infarction, CETP deficiency, CYP7A1 deficiency, hypoalphalipoproteinemia, veterinary and neurodevelopmental entries) rest on indirect or no evidence and should be held.
Clinical Trial Evidence
Many trials list atorvastatin as background or comparator therapy. Only some test atorvastatin itself.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00827606 | Phase 3 | Completed | 272 | 3-year open-label study of atorvastatin in children and adolescents with heterozygous FH: growth, development, and cholesterol reduction |
| NCT00134485 | Phase 3 | Completed | 400 | Torcetrapib/atorvastatin vs maximally tolerated atorvastatin alone in heterozygous FH (torcetrapib programme later terminated for safety) |
| NCT00136981 | Phase 3 | Completed | 800 | 24-month carotid ultrasound study of torcetrapib/atorvastatin vs atorvastatin alone in heterozygous FH |
| NCT00134511 | Phase 3 | Completed | 30 | Open-label forced-titration torcetrapib/atorvastatin in homozygous FH (small study; torcetrapib programme terminated for safety) |
| NCT03884452 | Phase 3 | Completed | 50 | Ezetimibe added to atorvastatin or simvastatin in homozygous FH |
| NCT03885921 | Phase 3 | Completed | 44 | Long-term safety of ezetimibe plus atorvastatin or simvastatin in homozygous FH |
| NCT01709500 | Phase 3 | Completed | 249 | Alirocumab vs placebo in heterozygous FH on background lipid-modifying therapy (indirect for atorvastatin) |
| NCT03510884 | Phase 3 | Completed | 153 | Alirocumab vs placebo in children and adolescents with heterozygous FH on statin background |
| NCT00739999 | Phase 1 | Completed | 39 | Pharmacokinetics, pharmacodynamics, and safety of atorvastatin in children and adolescents with heterozygous FH |
| NCT01279590 | Phase 2 | Completed | 282 | PPD10558 vs atorvastatin on statin-associated myalgia in statin-intolerant patients |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 25760954 | 2015 | Review (Cochrane) | Cochrane Database Syst Rev | Dose-related magnitude of atorvastatin's lipid-lowering effect |
| 27678432 | 2016 | Cohort | J Clin Lipidol | 3-year efficacy and safety of atorvastatin in children and adolescents with heterozygous FH |
| 9793596 | 1998 | Review | Ann Pharmacother | Efficacy and safety of atorvastatin in primary hypercholesterolemia and mixed dyslipidaemias |
| 28437620 | 2017 | Guideline | Endocr Pract | AACE/ACE guidelines for dyslipidaemia management and cardiovascular prevention |
| 15199433 | 2004 | Review | Semin Vasc Med | Diagnosis and treatment of FH in children |
| 11383320 | 2001 | Comparative study | Nutr Metab Cardiovasc Dis | Atorvastatin vs simvastatin for LDL-C goal attainment in heterozygous FH |
| 9301631 | 1997 | Open-label study | Arterioscler Thromb Vasc Biol | Atorvastatin 80 mg effective and well tolerated in FH (22 subjects) |
| 12883464 | 2003 | Clinical study | Med Sci Monit | Atorvastatin reduced microalbuminuria in FH patients |
| 27417002 | 2016 | Cohort | J Am Coll Cardiol | Statins and coronary artery disease and all-cause mortality in heterozygous FH |
| 17727860 | 2008 | Comparative study | Atherosclerosis | Rosuvastatin vs atorvastatin 80 mg in homozygous FH |
Singapore Market Information
All 20 licences are valid single-ingredient oral film-coated tablets, and none carries approved indication text in the compiled data. Five main authorisations:
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN09552P | LIPITOR Tablet 10 mg | Film-coated tablet | Not available |
| SIN09550P | LIPITOR Tablet 20 mg | Film-coated tablet | Not available |
| SIN09551P | LIPITOR Tablet 40 mg | Film-coated tablet | Not available |
| SIN15795P | ATOCOR 10 Film Coated Tablet 10 mg | Film-coated tablet | Not available |
| SIN14217P | ATORIS Film-coated Tablet 20 mg | Film-coated tablet | Not available |
Safety Considerations
- Contraindications (knowledge-graph derived, not label text): liver failure and liver disease, kidney disease, gallbladder disease, hypothyroidism (including myxedema and congenital hypothyroidism), myopathy and other muscle diseases, rhabdomyolysis, familial periodic paralysis, hypotensive disorder, and substance abuse/dependence.
- Drug Interactions: 100 interactions were found. Notable examples:
- Major: clarithromycin.
- Moderate: aprepitant, cimetidine, clotrimazole, dexamethasone, eliglustat, eluxadoline, metronidazole, miconazole, naltrexone, pectin, rosuvastatin, simvastatin, and the proton pump inhibitors (omeprazole, esomeprazole, lansoprazole, pantoprazole).
- Minor: aluminium hydroxide, magnesium hydroxide, liraglutide.
- For HIV-related use, CYP3A4 interactions with protease inhibitors and boosters require dose guardrails.
Package insert warnings and contraindications were not available. Please refer to the package insert for the full safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Familial hypercholesterolemia is supported by multiple completed Phase 3 trials, including a 3-year paediatric study of atorvastatin itself and randomised comparisons against atorvastatin alone, and by guideline and review literature. The use is on-label or label-adjacent, so this is better regarded as confirming existing use than as a true repurposing finding. The other nine predictions are not supported: HIV infection is a research question only (L2, small mixed studies), and the rest should be held.
To proceed, the following is needed:
- Singapore package insert content (indications, warnings, contraindications), which was not available for this report.
- Detailed mechanism of action data from DrugBank.
- Confirmation that the Singapore-approved indications cover familial hypercholesterolemia (heterozygous and homozygous).
- Dosing and monitoring guardrails for paediatric use, hepatic and renal impairment, and muscle toxicity risk.
- A CYP3A4 interaction management plan (e.g. clarithromycin, protease inhibitors).
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.