Meta-analysis · Lancet 2022
CTT 2022 muscle
Effect of statin therapy on muscle symptoms: an individual participant data meta-analysis of large-scale, randomised, double-blind trials.
The bottom line
Statins cause a small, mostly mild excess of muscle pain primarily in the first year of treatment, with over 90% of muscle symptom reports in statin users not actually due to the statin, and this risk is far outweighed by cardiovascular benefits.
Adverse-effect signal (small)US status: Not applicable
At a glance
- Medicine
- Statin therapy (various statins; also more intensive regimens such as 40-80 mg atorvastatin or 20-40 mg rosuvastatin once per day)
- Compared with
- Placebo (19 trials, n=123 940) or less intensive statin regimen (4 trials, n=30 724)
- People
- 154,664
- Who took part
- Participants in large-scale, long-term, randomised, double-blind trials of statin therapy; 19 placebo-controlled trials (mean age 63 years [SD 8], 27.9% women, 48.1% with previous vascular disease, 18.5% with diabetes) and 4 trials of more vs less intensive statin regimens
- Design
- Individual participant data meta-analysis of randomised, double-blind trials
- Follow-up
- Weighted average median follow-up of 4.3 years
- Main question
- Muscle pain or weakness reported by participants
Main result
16 835 (27.1%) allocated statin versus 16 446 (26.6%) allocated placebo reported muscle pain or weakness (rate ratio [RR] 1.03; 95% CI 1.01-1.06); during year 1, RR 1.07 (1.04-1.10); after year 1, RR 0.99 (0.96-1.02)
Effect on LDL cholesterol
''
Other results
For all years combined, more intensive statin regimens yielded a higher RR than less intensive or moderate-intensity regimens (1.08 [1.04-1.13] vs 1.03 [1.00-1.05]) compared with placebo, with a small excess (1.05 [0.99-1.12]) for more intensive regimens after year 1
Safety
Statin therapy yielded a small, clinically insignificant increase in median creatine kinase values of approximately 0.02 times the upper limit of normal; an absolute excess rate of 11 (6-16) events per 1000 person-years in year 1
In the trial's own words
“During year 1, statin therapy produced a 7% relative increase in muscle pain or weakness (1·07; 1·04-1·10), corresponding to an absolute excess rate of 11 (6-16) events per 1000 person-years, which indicates that only one in 15 ([1·07-1·00]/1·07) of these muscle-related reports by participants allocated to statin therapy were actually due to the statin. After year 1, there was no significant excess in first reports of muscle pain or weakness (0·99; 0·96-1·02).”
Quoted from the abstract of Lancet 2022, checked word for word against PubMed. PubMed 36049498 · Full paper (DOI)
Common questions
What did the CTT 2022 muscle trial find?
Statins cause a small, mostly mild excess of muscle pain primarily in the first year of treatment, with over 90% of muscle symptom reports in statin users not actually due to the statin, and this risk is far outweighed by cardiovascular benefits.
Who was in CTT 2022 muscle?
154,664 people. Participants in large-scale, long-term, randomised, double-blind trials of statin therapy; 19 placebo-controlled trials (mean age 63 years [SD 8], 27.9% women, 48.1% with previous vascular disease, 18.5% with diabetes) and 4 trials of more vs less intensive statin regimens.
What was CTT 2022 muscle's main result?
16 835 (27.1%) allocated statin versus 16 446 (26.6%) allocated placebo reported muscle pain or weakness (rate ratio [RR] 1.03; 95% CI 1.01-1.06); during year 1, RR 1.07 (1.04-1.10); after year 1, RR 0.99 (0.96-1.02)
How much did LDL cholesterol change in CTT 2022 muscle?
''
Related trials
- PCSK9/ezetimibe diabetes meta-analysis (2020)Neither PCSK9 inhibitors nor ezetimibe increase the risk of new-onset diabetes when added to guideline-directed medical therapy.
- CTT 2024 diabetes (2024)Statins cause a modest, dose-dependent increase in new-onset diabetes and worsening glycaemia, driven by small upward shifts in glucose/HbA1c, but this risk is already outweighed by the overall cardiovascular benefit of statin therapy.
- CTT 2019 older people (2019)Statins reduce major vascular events across all age groups including older people, though the evidence for benefit beyond age 75 without pre-existing vascular disease is less direct and being addressed by further trials.
- PCSK9 vs statin monotherapy meta-analysis (2026)In patients who cannot tolerate statins, PCSK9 inhibitor monotherapy lowers LDL-C, ApoB, and raises HDL-C more than high-intensity statin monotherapy, though it is less effective at lowering triglycerides.
Get your LDL treated to a goal
Preval Health's protocols follow trials like this one. Licensed clinicians set your goal, prescribe and recheck until you reach it.
Get startedEducation only, not medical advice. Results describe the people in this trial and can differ for you. Talk with your clinician before starting or stopping any medicine. Back to all 106 trials.