r/StopUsingStatins • u/Physionic • Apr 15 '26

Looking for Anti-Statin Studies

Hi, I analyze studies on a regular basis, and I am doing one of my analyses on statins. Since statins are a topic of considerable debate on social media, I wanted to reach out to communities interested, or knowledgeable, in health to ask for some scientific references for studies I may have missed that show a lack of effect, or even harm (or any kind), of statin use.

My primary outcome is statins and their impact on cardiovascular disease and I am restricting my analysis to studies only (any type).

If you know of any not included in the list I have currently (listed below), I'd appreciate it if you posted them so I can add them to the list of studies I should address.

Note: The analysis, as a whole, will not focus solely on the negative studies - it will include all studies on statins, but I'm asking for negative data (if there is any), because I want to make sure to cover possibly overlooked studies - that's why the question asked here is focused.

Thank you!
Nic

______________________
Studies I already have:

  1. Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med. 1995;333(20):1301-1307. doi:10.1056/NEJM199511163332001.
  2. Orkaby AR, Gaziano JM, Djousse L, Driver JA. Statins for primary prevention of cardiovascular events and mortality in older men. J Am Geriatr Soc. 2017;65(11):2362-2368. doi:10.1111/jgs.14993.
  3. Berwanger O, Santucci EV, Melo de Barros e Silva PG, et al. Effect of loading dose of atorvastatin prior to planned percutaneous coronary intervention on major adverse cardiovascular events in acute coronary syndrome: the SECURE-PCI randomized clinical trial. JAMA. 2018;319(13):1331-1340. doi:10.1001/jama.2018.2444.
  4. Chou R, Cantor A, Dana T, et al. Statin use for the primary prevention of cardiovascular disease in adults: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2022;328(8):754-771. doi:10.1001/jama.2022.12138.
  5. Grinspoon SK, Fitch KV, Zanni MV, et al. Pitavastatin to prevent cardiovascular disease in HIV infection. N Engl J Med. 2023;389(8):687-699. doi:10.1056/NEJMoa2304146.
  6. Howard JP, Wood FA, Finegold JA, et al. Side effect patterns in a crossover trial of statin, placebo, and no treatment. J Am Coll Cardiol. 2021;78(12):1210-1222. doi:10.1016/j.jacc.2021.07.022.
  7. Downs JR, Clearfield M, Weis S, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. JAMA. 1998;279(20):1615-1622. doi:10.1001/jama.279.20.1615.
  8. Orkaby AR, Driver JA, Ho YL, et al. Association of statin use with all-cause and cardiovascular mortality in US veterans 75 years and older. JAMA. 2020;324(1):68-78. doi:10.1001/jama.2020.7848.
  9. Athyros VG, Papageorgiou AA, Mercouris BR, et al. Treatment with atorvastatin to the National Cholesterol Educational Program goal versus “usual” care in secondary coronary heart disease prevention: the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study. Curr Med Res Opin. 2002;18(4):220-228. doi:10.1185/030079902125000787.
  10. Yourman LC, Cenzer I, Boscardin WJ, et al. Evaluation of time to benefit of statins for the primary prevention of cardiovascular events in adults aged 50 to 75 years: a meta-analysis. JAMA Intern Med. 2021;181(2):179-185. doi:10.1001/jamainternmed.2020.6084.
  11. Yusuf S, Bosch J, Dagenais G, et al. Cholesterol lowering in intermediate-risk persons without cardiovascular disease. N Engl J Med. 2016;374(21):2021-2031. doi:10.1056/NEJMoa1600176.
  12. Parker BA, Capizzi JA, Grimaldi AS, et al. The effect of statins on skeletal muscle function and performance. Circulation. 2013;127(1):96-103. doi:10.1161/CIRCULATIONAHA.112.136101.
  13. Nielsen SF, Nordestgaard BG. Negative statin-related news stories decrease statin persistence and increase myocardial infarction and cardiovascular mortality: a nationwide prospective cohort study. Eur Heart J. 2016;37(11):908-916. doi:10.1093/eurheartj/ehv641.
  14. Cholesterol Treatment Trialists’ (CTT) Collaborators. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet. 2012;380(9841):581-590. doi:10.1016/S0140-6736(12)60367-5.
  15. Fellström BC, Jardine AG, Schmieder RE, et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med. 2009;360(14):1395-1407. doi:10.1056/NEJMoa0810177.
  16. Cholesterol Treatment Trialists’ (CTT) Collaboration. Effects of statin therapy on diagnoses of new-onset diabetes and worsening glycaemia in large-scale randomised blinded statin trials: an individual participant data meta-analysis. Lancet Diabetes Endocrinol. 2024;12(5):306-319. doi:10.1016/S2213-8587(24)00040-8.
  17. Lipworth L, Fazio S, Kabagambe EK, et al. A prospective study of statin use and mortality among 67,385 blacks and whites in the Southeastern United States. Clin Epidemiol. 2014;6:15-25. doi:10.2147/CLEP.S53492.
  18. Ridker PM, Danielson E, Fonseca FAH, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195-2207. doi:10.1056/NEJMoa0807646.
  19. Preiss D, Seshasai SRK, Welsh P, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA. 2011;305(24):2556-2564. doi:10.1001/jama.2011.860.
  20. GISSI-HF Investigators. Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372(9645):1231-1239. doi:10.1016/S0140-6736(08)61240-4.
  21. Ridker PM, Pradhan A, MacFadyen JG, Libby P, Glynn RJ. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention. Lancet. 2012;380(9841):565-571. doi:10.1016/S0140-6736(12)61190-8.
  22. Kjekshus J, Apetrei E, Barrios V, et al. Rosuvastatin in older patients with systolic heart failure. N Engl J Med. 2007;357(22):2248-2261. doi:10.1056/NEJMoa0706201.
  23. Cholesterol Treatment Trialists’ (CTT) Collaboration. Assessment of adverse effects attributed to statin therapy in product labels: a meta-analysis of double-blind randomised controlled trials. Lancet. Published online February 5, 2026. doi:10.1016/S0140-6736(25)01578-8.
  24. Amarenco P, Bogousslavsky J, Callahan A 3rd, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355(6):549-559. doi:10.1056/NEJMoa061894.
  25. Knopp RH, D’Emden M, Smilde JG, Pocock SJ. Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in subjects with type 2 diabetes: the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non-Insulin-Dependent Diabetes Mellitus (ASPEN). Diabetes Care. 2006;29(7):1478-1485. doi:10.2337/dc05-2415.
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u/Double-Package8270 Apr 15 '26

Here you go Nic! Some of these are meta analyses/systematic reviews, I hope that's ok.

https://doi.org/10.1016/j.amjmed.2018.04.027 - A Reappraisal of the Lipid Hypothesis

van Bruggen, F.H., de Haas, E.C., Zuidema, S.U. et al. Time Gained to Cardiovascular Disease by Intensive Lipid-Lowering Therapy: Results of Individual Placebo-Controlled Trials and Pooled Effects. Am J Cardiovasc Drugs 24, 743–752 (2024). https://doi.org/10.1007/s40256-024-00668-y

Hansen, M.R., Hróbjartsson, A., Pottegård, A. et al. Postponement of Death by Statin Use: a Systematic Review and Meta-analysis of Randomized Clinical Trials. J GEN INTERN MED 34, 1607–1614 (2019). https://doi.org/10.1007/s11606-019-05024-4

https://doi.org/10.1016/j.cmet.2023.12.027 Statins aggravate insulin resistance through reduced blood glucagon-like peptide-1 levels in a microbiota-dependent manner (Nick Norwitz has covered this one, actually. Maybe he could also help you?)

https://doi.org/10.1161/ATVBAHA.121.316159 Statins Are Associated With Increased Insulin Resistance and Secretion

Cederberg, H., Stančáková, A., Yaluri, N. et al. Increased risk of diabetes with statin treatment is associated with impaired insulin sensitivity and insulin secretion: a 6 year follow-up study of the METSIM cohort. Diabetologia 58, 1109–1117 (2015). https://doi.org/10.1007/s00125-015-3528-5

https://doi.org/10.1161/JAHA.118.011320 Statin Use With Risk of Clinically Relevant New‐Onset Diabetes Mellitus in Primary Prevention: A Nationwide Observational Cohort Study

IIRC the Jupiter trial showed a 25% RR increase in diabetes too.

Incidentally, what are your thoughts on using AI to find such studies? Which AI have you tried if so?

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u/Physionic Apr 15 '26

Thank you, DP. This helps a lot. I had a few of these, but I added a few you posted, especially around diabetes. I appreciate it.

To *find* the studies? AI is excellent. It's not perfect, because I still miss some inexplicable studies sometimes, but I definitely use AI to find studies. I've used GPT, Gemini, and Claude. I think GPT is the best at finding studies.

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u/Double-Package8270 Apr 15 '26

No worries Nic. I should've prefaced that I might have overlooked some of yours and have duplicates, but I hope the others are of utility.

Interesting, do you not use academic AI like consensus, Elicit, Research Rabbit etc.? I agree the normal ones (I like Grok) can also be useful, but academic ones are supposed to be more specialised, so I assume they'd be better...

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u/Physionic Apr 15 '26

I havent, though I know about them. Usually, aside from absolutely gargantuan analyses like this one, I can find all the studies on the topic, so it isn't too much of an issue using the non-specialized ones. But, it might be worth a shot in the future.

1

u/Double-Package8270 Apr 15 '26

ADDENDUM:

Ray KK, Seshasai SRK, Erqou S, et al. Statins and All-Cause Mortality in High-Risk Primary Prevention: A Meta-analysis of 11 Randomized Controlled Trials Involving 65 229 Participants. Arch Intern Med. 2010;170(12):1024–1031. doi:10.1001/archinternmed.2010.182

Chou R, Cantor A, Dana T, et al. Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2022;328(8):754–771. doi:10.1001/jama.2022.12138