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Research · Medication

Statins

Pooled trials of about 170,000 people found each 1 mmol/L drop in LDL cholesterol on a statin cut major vascular events by about a fifth, including in low-risk people. Muscle pain rose slightly, mostly in year one, and most reported pain was not caused by the statin. New diabetes rose 9%. Training study results were mixed.

Add to Bio HackChecked 2026-11-09
Status
Prescription drugs in the US, FDA-approved to lower LDL cholesterol and reduce the risk of cardiovascular events.
Also called
atorvastatin, Lipitor, rosuvastatin, Crestor, simvastatin, Zocor, pravastatin, lovastatin, pitavastatin, HMG-CoA reductase inhibitor
Taken for
cholesterol, LDL, heart attack prevention, stroke prevention, heart health, muscle gain with training

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

What people take it for, and what was found

Shown to help3

Strong

Heart attack, stroke and death

Shown to cut major vascular events about 22% and deaths about 10% for each 1 mmol/L drop in LDL cholesterol, including in lower-risk people.

The numbers and sources
Effect
Per 1.0 mmol/L reduction in LDL cholesterol, major vascular events fell with a rate ratio of 0.78 (95% CI 0.76 to 0.80) and all-cause mortality with 0.90 (95% CI 0.87 to 0.93). More intensive regimens cut major vascular events a further 15% (95% CI 11 to 18) against less intensive ones [1]. In people with a 5-year risk under 10%, each 1 mmol/L reduction cut major vascular events by about 11 per 1,000 over 5 years. In people without vascular disease, all-cause mortality RR was 0.91 (95% CI 0.85 to 0.97) per 1 mmol/L [2].
Population
Individual data from 26 trials with about 170,000 participants, median follow-up about 5 years [1]; 27 trials with 174,149 participants, grouped by baseline risk [2].
Sources
[1], [2]
Caveats
Both analyses come from the same collaboration, and the same 5 intensity trials appear in both. Effects are expressed per unit of LDL lowered, not per drug or dose.
Moderate

LDL cholesterol lowering

Shown to lower LDL cholesterol by about 51 to 56 mg/dL with atorvastatin and rosuvastatin, and triglycerides by about 25 to 32 mg/dL.

The numbers and sources
Effect
Pooled across studies, atorvastatin lowered LDL cholesterol by 51.49 mg/dL (95% CI 42.75 to 60.23) and rosuvastatin by 55.66 mg/dL (95% CI 46.32 to 65.00). Triglycerides fell by 24.76 and 31.98 mg/dL, and HDL rose by 1.85 and 3.87 mg/dL [3].
Population
Studies of atorvastatin and rosuvastatin from 2003 to 2025 [3].
Sources
[3]
Caveats
The abstract does not give study counts, doses or the comparison used. The heart attack and stroke results above are expressed per unit of LDL lowered [1].
Limited

Lean mass gain with resistance training

Limited evidence: one 12-week study linked statin use to greater lean mass gains with resistance training in adults aged 60 to 69, without randomizing statin use.

The numbers and sources
Effect
In a 12-week resistance training study, statin use was associated with greater gains in lean mass [4].
Population
49 community-dwelling adults aged 60 to 69 [4].
Sources
[4]
Caveats
Statin use was not randomized, and the abstract gives no effect size. It reports an association, not a cause.

Doses studied

The muscle symptom meta-analysis defined more intensive regimens as 40 to 80 mg atorvastatin or 20 to 40 mg rosuvastatin once daily [5]. The n-of-1 trials used atorvastatin 20 mg daily [6]. The aerobic training trial used simvastatin 40 mg a day [7]. The trial in adults aged 70 and older used atorvastatin 40 mg once daily [8].

Risks

Reported risks4

StrongVery common

Muscle pain and weakness

Shown to raise muscle pain or weakness slightly in year 1, about 1 in 15 reports, with no excess after. In people with past symptoms, symptoms matched placebo.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Over a median 4.3 years, 27.1% on a statin and 26.6% on placebo reported muscle pain or weakness (RR 1.03, 95% CI 1.01 to 1.06). In year 1 the excess was 7% (RR 1.07), or 11 more reports per 1,000 person-years, meaning about 1 in 15 reports on a statin was caused by it. After year 1 there was no significant excess. More intensive regimens had a higher RR (1.08) than moderate ones (1.03). Creatine kinase rose by about 0.02 times the upper limit of normal [5]. In people who had stopped statins over muscle symptoms, symptom scores did not differ between atorvastatin and placebo periods (MD -0.11, 95% CI -0.36 to 0.14). Withdrawals for intolerable symptoms were 9% during statin periods and 7% during placebo periods [6].
Population
123,940 participants in 19 placebo-controlled trials and 30,724 in 4 intensity trials [5]; 200 people in UK primary care, 151 analyzed, each randomized through six 2-month periods [6].
Sources
[5], [6]
Caveats
The n-of-1 series enrolled only people who had already reported muscle symptoms on statins [6]. The meta-analysis covers large trials of at least 1,000 people lasting at least 2 years [5].
ModerateUncommon

Liver enzyme rises and severe muscle injury

Shown to raise liver enzymes in about 0.2% on high doses. Severe muscle injury rose with dose, and myopathy was more frequent on simvastatin 80 mg.

The numbers and sources
How common
Uncommon: between 1 in 1,000 and 1 in 100 people.
Effect
Across 41 RCTs, transaminase elevation on high-dose statins occurred at a rate of 0.2% (95% CI 0.004 to 0.4%), and creatine kinase rises under three times the upper limit at 0.43% (95% CI 0.11 to 0.75%). Rhabdomyolysis risk rose with dose, and myopathy was more frequent on simvastatin 80 mg than on other statins [9].
Population
64,728 participants in 41 RCTs across several diseases [9].
Sources
[9]
Caveats
Rates varied by disease group, and the abstract does not give the rhabdomyolysis rate [9].
LimitedHow often is not known

Autoimmune hepatitis

Limited evidence: statins appeared in 9% of FDA autoimmune hepatitis reports, strongest for fluvastatin. Spontaneous reports cannot give a rate or prove cause.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
In the FDA adverse event database from 2004 to 2024, 337 of 3,581 autoimmune hepatitis reports (9.41%) involved statins. Fluvastatin had the strongest signal (reporting odds ratio 54.85, 95% CI 32.32 to 93.10), and signals were stronger in people 65 and older and in women. The review also summarized 30 published cases [10].
Population
Spontaneous reports and 30 published cases [10].
Sources
[10]
Caveats
Spontaneous reports cannot give a rate or prove cause.
LimitedHow often is not known

Interaction with some antibiotics

Limited evidence: statins with some antibiotics, mainly macrolides, were linked to about twice the muscle toxicity of a statin alone, in three observational studies.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Taking a statin with an interacting antibiotic, mainly macrolides, was associated with more statin-related muscle toxicity than a statin alone (OR 2.13, 95% CI 1.82 to 2.50) [13].
Population
3 observational studies [13].
Sources
[13]
Caveats
Only three studies, all observational [13].

Mixed results3

LimitedHow often is not known

Tendon problems

Limited evidence: tendon rupture was not more common in statin users. Other observational studies linked statins to trigger finger, Achilles tendinitis and rotator cuff retears.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
In a cohort of over 1 million people, native tendon rupture did not rise among statin users (HR 0.95, 95% CI 0.84 to 1.08). Other studies linked statin use to trigger finger (HR 1.435), radial styloid tenosynovitis (HR 1.365) and Achilles tendinitis (HR 1.516), and one retrospective study found more retears after rotator cuff repair (OR 6.5) [11]. Three cohort studies on shoulder tendinopathy gave conflicting results [12].
Population
12 studies, 8 on native tendons and 4 after tendon repair [11]; 3 cohort studies [12].
Sources
[11], [12]
Caveats
Observational studies with mixed results by tendon, sex and statin type [11].
LimitedHow often is not known

Blunted fitness gains from training

Small trials found mixed results: one found simvastatin blunted fitness gains from aerobic training, and others found similar gains in statin users and non-users.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Results differ by trial. Over 12 weeks of aerobic training, fitness rose 10% with exercise alone and 1.5% with simvastatin, and muscle citrate synthase rose 13% against a 4.5% fall [7]. Over 16 weeks of interval training, VO2 peak rose 12% in statin users and 19% in non-users, while metabolic syndrome scores, fat oxidation and mitochondrial enzymes improved similarly [15]. Over 12 weeks of endurance and resistance training, strength, fatigue resistance and capillarization improved with no differences between statin users and controls; citrate synthase improved less in statin users without symptoms [16].
Population
37 sedentary overweight adults with metabolic syndrome risk factors, randomized [7]; 106 adults with metabolic syndrome, statin users and matched non-users [15]; 32 statin users and 20 controls, mean age 63 to 64 [16].
Sources
[7], [15], [16]
Caveats
Small trials, and only [7] randomized statin use. No meta-analysis was sourced.
ModerateHow often is not known

New type 2 diabetes

Mixed results: one review found 9% higher odds of new type 2 diabetes, one extra case per 255 treated for 4 years, while a 2026 review found no significant rise.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Statin therapy raised the odds of new diabetes by 9% (OR 1.09, 95% CI 1.02 to 1.17), with little heterogeneity. Treating 255 people for 4 years produced one extra case. Risk was highest in trials of older participants [17]. A 2026 network meta-analysis found no significant difference in new diabetes between individual statins or against placebo, with higher point estimates for rosuvastatin 20 mg and atorvastatin 80 mg [18]. Pravastatin did not show a lower risk than atorvastatin (RR 1.01, 95% CI 0.77 to 1.32) or rosuvastatin (RR 1.12, 95% CI 0.85 to 1.47) [19].
Population
91,140 participants in 13 randomized statin trials, mean 4 years [17]; 99,311 patients in 22 RCTs [18]; 10 studies comparing pravastatin with other statins [19].
Sources
[17], [18], [19]
Caveats
Baseline BMI and change in LDL cholesterol did not explain the remaining variation in risk between trials [17]. The two pooled analyses of randomized trials disagree on whether risk rises [17][18]. The pravastatin comparison had very high heterogeneity (I² 96 to 98%) [19].

Possible, not studied in people1

Untested

Male reproductive effects in animals

Not studied in people. In healthy male rodents, statins were linked to lower sperm quality and testosterone, with the opposite in diseased rodents.

No study in people. This rests on animal studies.

The numbers and sources
Effect
In healthy male rodents, statin exposure was linked to lower sperm quality, lower testosterone production and delayed puberty. In diseased rodents, findings went the other way [14].
Population
Male rats and mice (animal), plus in vitro studies [14].
Sources
[14]
Caveats
Animal and in vitro data only. No human reproductive outcomes were measured [14].

Claims tested and not found

  1. That most muscle pain reported on statins is caused by the statin. In blinded trials, over 90% of muscle symptom reports on a statin were not due to the statin [5], and in people who had stopped over symptoms, scores did not differ from placebo [6].
  2. That statins raise cancer risk. Cancer incidence did not differ per 1 mmol/L LDL reduction (RR 1.00, 95% CI 0.96 to 1.04) [1][2].
  3. That statins cause dementia or memory loss. In a meta-analysis of 35 cohort studies, statin use was associated with lower dementia risk (HR 0.79, 95% CI 0.71 to 0.88) and lower Alzheimer risk (HR 0.71, 95% CI 0.60 to 0.85) [20]. A second meta-analysis of 34 observational studies also found lower dementia risk [21]. In 181 people with HIV in a randomized trial, neurocognitive scores did not differ between pitavastatin and placebo over a median 2.3 years [22].
  4. That statins raise the risk of bleeding in the brain. A network meta-analysis of RCTs found no significant rise in intracerebral hemorrhage for any statin against placebo [23].
  5. That statins lengthen disability-free life in people over 70. In 9,971 adults aged 70 and older without cardiovascular disease, diabetes or dementia, atorvastatin cut major cardiovascular events (HR 0.70, 95% CI 0.61 to 0.82) but did not change the composite of death, dementia or persistent disability (HR 0.94, 95% CI 0.84 to 1.05) over a median 5.9 years [8].
  6. That statins reduce muscle size or physical function. In a randomized trial of pitavastatin in people with HIV, chair rise rate, gait speed and grip strength did not differ from placebo over a median 4.7 years [24], and CT muscle area and density did not change over 24 months [25].

Sources

  1. Cholesterol Treatment Trialists' (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials. The Lancet. 2010. https://doi.org/10.1016/S0140-6736(10)61350-5
  2. 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. The Lancet. 2012. https://doi.org/10.1016/S0140-6736(12)60367-5
  3. Sayehmiri K, Shohani M, Qavam S, et al. Comparing the effectiveness of Rosuvastatin and Atorvastatin on changes in LDL, TG and HDL: A systematic review and meta-analysis. Life Sciences. 2025. https://doi.org/10.1016/j.lfs.2025.123576
  4. Riechman SE, Andrews RD, MacLean DA, et al. Statins and Dietary and Serum Cholesterol Are Associated With Increased Lean Mass Following Resistance Training. The Journals of Gerontology Series A. 2007. https://doi.org/10.1093/gerona/62.10.1164
  5. Reith C, Baigent C, Blackwell L, et al. Effect of statin therapy on muscle symptoms: an individual participant data meta-analysis of large-scale, randomised, double-blind trials. The Lancet. 2022. https://doi.org/10.1016/S0140-6736(22)01545-8
  6. Herrett E, Williamson E, Brack K, et al. Statin treatment and muscle symptoms: series of randomised, placebo controlled n-of-1 trials. BMJ. 2021. https://doi.org/10.1136/bmj.n135
  7. Mikus CR, Boyle LJ, Borengasser SJ, et al. Simvastatin Impairs Exercise Training Adaptations. Journal of the American College of Cardiology. 2013. https://doi.org/10.1016/j.jacc.2013.02.074
  8. Zoungas S, Wolfe R, Moran C, et al. Atorvastatin, Cardiovascular Events, and Disability-free Survival in Older Adults. New England Journal of Medicine. 2026. https://doi.org/10.1056/nejmoa2607314
  9. Li W, Wang D, Lin C, et al. A Meta-Analysis of the Incidence of Adverse Reactions of Statins in Various Diseases. Cardiovascular Therapeutics. 2025. https://doi.org/10.1155/cdr/6684099
  10. Pan C, Zhou X, Wang Y, et al. Autoimmune hepatitis associated with statins: a retrospective study of pharmacovigilance databases and review of the literature. Expert Opinion on Drug Safety. 2025. https://doi.org/10.1080/14740338.2025.2449986
  11. Anzillotti G, Vespasiano F, Öttl F, et al. Statins: bitter enemies of tendons or not? A systematic review of clinical evidence. European Review for Medical and Pharmacological Sciences. 2025. https://pubmed.ncbi.nlm.nih.gov/41182304/
  12. Manocchio N, Pirri C, Sorbino A, et al. Shoulder Tendinopathy Induced by Statins: A Case Report and Systematic Review. Journal of Personalized Medicine. 2025. https://doi.org/10.3390/jpm15050198
  13. Tripathi T, Verma N, Gupta K, et al. Drug-drug interactions between statins and antibiotics: A systematic review and meta-analysis of observational studies. Indian Journal of Pharmacology. 2026. https://doi.org/10.4103/ijp.ijp_10_26
  14. Araújo Leite GA, Lazzari VM, Simão VA, et al. Effects of statins on male reproductive health: a systematic review of rodent studies and their potential implications to human male reproduction. Critical Reviews in Toxicology. 2025. https://doi.org/10.1080/10408444.2025.2504395
  15. Morales-Palomo F, Ramirez-Jimenez M, Ortega JF, et al. Exercise Training Adaptations in Metabolic Syndrome Individuals on Chronic Statin Treatment. The Journal of Clinical Endocrinology & Metabolism. 2020. https://doi.org/10.1210/clinem/dgz304
  16. Allard NA, Janssen L, Aussieker T, et al. Moderate Intensity Exercise Training Improves Skeletal Muscle Performance in Symptomatic and Asymptomatic Statin Users. Journal of the American College of Cardiology. 2021. https://doi.org/10.1016/j.jacc.2021.08.075
  17. Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. The Lancet. 2010. https://doi.org/10.1016/S0140-6736(09)61965-6
  18. Xue Q, Wang F, Zhang Y, et al. Risk of hyperglycemia with different statins by type and dose: a network meta-analysis and real-world pharmacovigilance study. Frontiers in Pharmacology. 2026. https://doi.org/10.3389/fphar.2026.1867316
  19. Singh H, Kaur G, Kaushal P. Comparative risk of new-onset diabetes between pravastatin and commonly used statins: A systematic review and meta-analysis. International Journal of Risk & Safety in Medicine. 2026. https://doi.org/10.1177/09246479261476847
  20. Du Y, Yu Z, Li C, et al. The role of statins in dementia or Alzheimer's disease incidence: a systematic review and meta-analysis of cohort studies. Frontiers in Pharmacology. 2025. https://doi.org/10.3389/fphar.2025.1473796
  21. Li X, Liu Y, Song T, et al. Statins and the risk of dementia: a meta-analysis. Acta Neurologica Belgica. 2025. https://doi.org/10.1007/s13760-025-02758-3
  22. Erlandson KM, McKhann A, Kitch DW, et al. No evidence of a detrimental effect of pitavastatin on neurocognitive function among people with HIV. AIDS. 2025. https://doi.org/10.1097/qad.0000000000004267
  23. Li W, Wu C, Li W, et al. LDL-cholesterol lowering agents (statins and PCSK9 inhibitors) and the risk of intracerebral hemorrhage: A network meta-analysis. Journal of Stroke and Cerebrovascular Diseases. 2025. https://doi.org/10.1016/j.jstrokecerebrovasdis.2025.108224
  24. Erlandson KM, Umbleja T, Ribaudo HJ, et al. Pitavastatin Is Well-Tolerated With no Detrimental Effects on Physical Function. Clinical Infectious Diseases. 2025. https://doi.org/10.1093/cid/ciae422
  25. Erlandson KM, Umbleja T, Ribaudo HJ, et al. No evidence of pitavastatin effect on muscle area or density among people with HIV. AIDS. 2025. https://doi.org/10.1097/qad.0000000000004306

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