Atorvastatin
| Evidence Level: L1 | Predicted Indications: 6 |
Table of Contents
- Atorvastatin
- Atorvastatin: From Lipid Lowering (Original Indication Not Recorded) to Familial Hypercholesterolaemia
Atorvastatin: From Lipid Lowering (Original Indication Not Recorded) to Familial Hypercholesterolaemia
One-Sentence Summary
Atorvastatin is a statin (HMG-CoA reductase inhibitor) used to lower cholesterol, and it is registered in South Africa under 9 SAHPRA registrations. The TxGNN model predicts it may be effective for familial hypercholesterolaemia (FH), with 35 registered clinical trials and 19 publications in this direction. This is most likely confirmation of an existing use rather than a genuinely new one, because the SAHPRA records provided do not state the approved indication.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the SAHPRA records provided (presumed lipid lowering/hypercholesterolaemia, to be verified against the Professional Information) |
| Predicted New Indication | Familial hypercholesterolaemia |
| TxGNN Prediction Score | 99.42% |
| Evidence Level | L1 |
| South Africa Market Status | Marketed |
| Number of SAHPRA Registrations | 9 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Atorvastatin inhibits HMG-CoA reductase, the key enzyme in hepatic cholesterol synthesis. This upregulates hepatic LDL receptors and lowers LDL cholesterol (LDL-C). FH is a genetic condition with markedly raised LDL-C and premature cardiovascular disease, and lowering LDL-C is the main treatment goal. The mechanistic link is therefore direct.
Because the original indication and mechanism fields are missing from the record, we cannot confirm whether FH is a label indication or a true repurposing candidate. It is very likely an existing use, so this prediction confirms known efficacy rather than a novel signal.
Response also differs by FH type. Homozygous FH usually needs add-on therapy, because LDL-receptor function is greatly reduced. Heterozygous FH generally responds better to statin therapy.
The score is not a discriminating signal. All six predictions for this drug score about 0.99, including ones with no supporting evidence.
Clinical Trial Evidence
Most trials tested atorvastatin as the comparator or background therapy, not as the experimental drug. The torcetrapib trials were part of a programme terminated in December 2006 for safety findings, so they support the atorvastatin arm only. The list below shows 10 of the 35 registered trials.
| 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, tracking growth and cholesterol reduction |
| NCT00134485 | Phase 3 | Completed | 400 | Randomised, double-blind trial of torcetrapib/atorvastatin vs maximally tolerated atorvastatin alone in heterozygous FH |
| NCT00136981 | Phase 3 | Completed | 800 | Randomised, double-blind carotid ultrasound study over 24 months, torcetrapib/atorvastatin vs atorvastatin alone in heterozygous FH |
| NCT00134511 | Phase 3 | Completed | 30 | Open-label forced-titration study of torcetrapib/atorvastatin in homozygous FH |
| NCT03884452 | Phase 3 | Completed | 50 | Ezetimibe added to atorvastatin or simvastatin in homozygous FH |
| NCT03885921 | Phase 3 | Completed | 44 | 24-month extension: long-term safety of ezetimibe with atorvastatin or simvastatin in homozygous FH |
| NCT03867318 | Phase 3 | Completed | 621 | Double-blind trial of ezetimibe added to atorvastatin 10 mg in heterozygous FH, coronary heart disease or multiple risk factors |
| NCT03882996 | Phase 3 | Completed | 432 | 12-month open-label safety extension of ezetimibe plus atorvastatin |
| NCT01730040 | Phase 3 | Completed | 355 | Alirocumab added to atorvastatin vs ezetimibe vs atorvastatin dose increase vs switch to rosuvastatin |
| NCT00739999 | Phase 1 | Completed | 39 | 8-week pharmacokinetics and safety of atorvastatin in children and adolescents with heterozygous FH |
Literature Evidence
None of the publications is labelled as an RCT in the data. The list is ordered by study type (meta-analysis and clinical studies, then reviews and guidelines).
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 27417002 | 2016 | Meta-analysis/Cohort | J Am Coll Cardiol | Quantifies statin-related reduction in coronary artery disease events and mortality in heterozygous FH |
| 27678432 | 2016 | Clinical study | J Clin Lipidol | 3-year atorvastatin use in children and adolescents with heterozygous FH, assessing efficacy and safety beyond 1 year |
| 11383320 | 2001 | Comparative study | Nutr Metab Cardiovasc Dis | Atorvastatin vs simvastatin for reaching LDL-C goals in heterozygous FH |
| 22957727 | 2013 | Clinical study | Echocardiography | Atorvastatin improved myocardial and peripheral blood flow in FH patients without coronary atherosclerosis |
| 39751968 | 2025 | Review | Curr Atheroscler Rep | New therapies for homozygous FH, co-authored by South African investigators |
| 28437620 | 2017 | Guideline | Endocr Pract | AACE/ACE guidelines for dyslipidaemia management and cardiovascular prevention |
| 9793596 | 1998 | Review | Ann Pharmacother | Efficacy and safety of atorvastatin in primary hypercholesterolaemia and mixed dyslipidaemia |
| 26988948 | 2016 | Review | J Am Coll Cardiol | Improving monitoring and care of patients with FH |
| 15199433 | 2004 | Review | Semin Vasc Med | Diagnostic, clinical and therapeutic aspects of FH in children |
| 30270066 | 2018 | Retrospective study | Atherosclerosis | Real-world FH treatment in Slovakia, showing many patients miss LDL-C goals despite statins |
South Africa Market Information
Five of the 9 registrations are shown. The indication text is empty in the records provided, and EML status was not included in the data.
| Registration Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| Reg. No. 43/7.5/0169 | Dynator | Tablet | Not stated in the records provided |
| Reg. No. 45/7.5/0447 | Atorvastatin lhc | Tablet | Not stated in the records provided |
| Reg. No. 43/7.5/0480 | Atorvastatin winthrop | Tablet | Not stated in the records provided |
| Reg. No. A39/7.5/0017 | Aspavor | Tablet | Not stated in the records provided |
| Reg. No. A39/7.0/0326 | Caduet 5mg/10mg | Tablet | Not stated in the records provided |
Safety Considerations
Please refer to the SAHPRA-approved Professional Information (PI) for safety information. Report adverse drug reactions to SAHPRA.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Several completed Phase 3 trials, including randomised comparisons, involve atorvastatin in FH, and the mechanism is direct. However, atorvastatin is mostly the comparator or background therapy in these trials, and the finding is probably confirmation of known use rather than new repurposing.
To proceed, the following is needed:
- Confirm the approved indication from the SAHPRA Professional Information and check whether FH is already on the label.
- Obtain warnings, contraindications and interactions from the PI. The interaction query returned no results, which is a data gap and not evidence of no interactions.
- Distinguish heterozygous from homozygous FH in any protocol, since homozygous FH usually needs add-on therapy.
- Follow guideline dosing and monitoring, including paediatric dosing where relevant.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.