Treatment strategies in patients with statin intolerance: the Cleveland Clinic experience
Open accessAbstract
Background Statin therapy is a proven effective treatment of hyperlipidemia. However, a significant number of patients cannot tolerate statins. This study was conducted to review treatment strategies for patients intolerant to statin therapy with a focus on intermittent statin dosing.Methods and results We performed a retrospective analysis of medical records of 1,605 patients referred to the Cleveland Clinic Preventive Cardiology Section for statin intolerance between January 1995 and March 2010 with at least a 6-month follow-up. The changes in lipid profile, achievement of low-density lipoprotein cholesterol (LDL-C) goals, and statin tolerance rate were analyzed. Most (72.5%) of patients with prior statin intolerance were able to tolerate a statin for the median follow-up time of 31 months. Patients on intermittent statin dosing (n = 149) had significantly lower LDL-C reduction compared with daily dosing group (n = 1,014; 21.3% ± 4.0% vs 27.7% ± 1.4%, P < .04). However, compared with the statin discontinued group (n = 442), they had a significantly higher LDL-C reduction (21.3% ± 4.0% vs 8.3 ± 2.2%, P < .001), and a significantly higher portion achieved their Adult Treatment Panel III goal of LDL-C (61% vs 44%, P < .05). There was a trend toward a decrease in all-cause mortality at 8 years for patients on daily and intermittent statin dosing compared with those who discontinued statin (P = .08).Conclusions Most patients with previous statin intolerance can tolerate subsequent trial of statin. A strategy of intermittent statin dosing can be an effective therapeutic option in some patients and may result in reduction in LDL-C and achievement of LDL-C goals.
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Three studies reported the incidence of muscle symptoms, five studies provided data on treatment discontinuation due to muscle symptoms, and eight studies reported on effectiveness.
“Three studies reported the incidence of muscle symptoms [36–38], five studies provided data on treatment discontinuation due to muscle symptoms [36,37,39,42,45], and eight studies reported on effectiveness [35–37,39,41,44,45,50].”
From Safety outcomes of statin vs non-statin lipid-lowering interventions in patients with prior statin-associated muscle symptoms: A systematic review and meta-analysis (2025) · cites this paper as [44]
The Results report myalgia as the most common intolerance complaint, statin discontinuation in 27.5% of patients, and LDL-C reductions and goal attainment, so this paper provides data relevant to muscle symptoms and effectiveness. It does not establish how many studies the citing review included, or specify that the reported discontinuations were due to muscle symptoms. (LLM, conf=0.84)
Experimental — accuracy not yet measuredAll 8 identified retrospective studies were of low quality, mainly due to concerns regarding residual confounding because of lack of adjustment.
“Notably all 8 identified retrospective studies were of low quality, mainly due to concerns regarding residual confounding because of lack of adjustment (S2 File) [35,36,38,41,42,44,45,50].”
The reduction in LDL-C levels was also around 20% with intermittent dosing of statin-therapy in a different study.
“In comparison, the reduction in LDL-C levels was also around 20% with intermittent dosing of statin-therapy in a different study [44].”
We included eight retrospective cohort studies and two prospective cohort studies.
“We included eight retrospective cohort studies [35,38,39,41,42,44,45,50] and two cohort prospective studies [36,37] (S4 File, Table 2).”
Similar results to Zhang et al. were reported by Mampuya et al.
“Similar results were reported by Mampuya et al.25”
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“Notably all 8 identified retrospective studies were of low quality, mainly due to concerns regarding residual confounding because of lack of adjustment (S2 File) [35,36,38,41,42,44,45,50].”
- Authors
- Mampuya, W. M., Frid, D., Rocco, M., Huang, J., Brennan, D. M., Hazen, S. L., & Cho, L.
- Affiliations
- Centre Hospitalier Universitaire de Sherbrooke (CA)
- Cleveland Clinic (US)
- Corresponding author
- Cho, Leslie
- Venue
- American Heart Journal
- Publisher
- Elsevier BV
- Published
- 2013-09
- Volume
- 166
- Issue
- 3
- Pages
- 597-603
- ISSN
- 0002-8703 (ISSN-L)
- PMC
- PMC4038261
- OpenAlex
- W1975636428
- Cited by
- 173
- References
- 35
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 3 · 2022: 11 · 2021: 15 · 2020: 12 · 2019: 15 · 2018: 17 · 2017: 16 · 2016: 33 · 2015: 22 · 2014: 14 · 2013: 4
- FWCI
- 23.97
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Heart Journal (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (P01HL076491, P01HL098055)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- statin intolerance, hyperlipidemia, LDL cholesterol lowering, LDL cholesterol targets, statin rechallenge, all-cause mortality, lipid-lowering therapy, preventive cardiology
- MeSH terms
- Adult, Aged, Female, Follow-Up Studies, Humans, Hyperlipidemias, Cholesterol, LDL, Male, Middle Aged, Patient Compliance, Retrospective Studies, Survival Analysis, Treatment Outcome, Hydroxymethylglutaryl-CoA Reductase Inhibitors
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