Side Effect Patterns in a Crossover Trial of Statin, Placebo, and No Treatment
Open accessAbstract
BACKGROUND: Most people who begin statins abandon them, most commonly because of side effects. OBJECTIVES: The purpose of this study was to assess daily symptom scores on statin, placebo, and no treatment in participants who had abandoned statins. METHODS: Participants received 12 1-month medication bottles, 4 containing atorvastatin 20 mg, 4 placebo, and 4 empty. We measured daily symptom intensity for each using an app (scale 1-100). We also measured the "nocebo" ratio: the ratio of symptoms induced by taking statin that was also induced by taking placebo. RESULTS: A total of 60 participants were randomized and 49 completed the 12-month protocol. Mean symptom score was 8.0 (95% CI: 4.7-11.3) in no-tablet months. It was higher in statin months (16.3; 95% CI: 13.0-19.6; P < 0.001), but also in placebo months (15.4; 95% CI: 12.1-18.7; P < 0.001), with no difference between the 2 (P = 0.388). The corresponding nocebo ratio was 0.90. In the individual-patient daily data, neither symptom intensity on starting (OR: 1.02; 95% CI: 0.98-1.06; P = 0.28) nor extent of symptom relief on stopping (OR: 1.01; 95% CI: 0.98-1.05; P = 0.48) distinguished between statin and placebo. Stopping was no more frequent for statin than placebo (P = 0.173), and subsequent symptom relief was similar between statin and placebo. At 6 months after the trial, 30 of 60 (50%) participants were back taking statins. CONCLUSIONS: The majority of symptoms caused by statin tablets were nocebo. Clinicians should not interpret symptom intensity or timing of symptom onset or offset (on starting or stopping statin tablets) as indicating pharmacological causation, because the pattern is identical for placebo. (Self-Assessment Method for Statin Side-effects Or Nocebo [SAMSON]; NCT02668016).
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In a randomized controlled trial, 90% of symptoms while on a statin also occurred while on placebo.
“A randomized controlled trial found 90% of symptoms while on a statin also occurred while on placebo [5].”
From Intolerance upon statin rechallenge: A systematic review and meta-analysis of randomized controlled trials (2023) · cites this paper as [5]
The Results (Symptom scores for statin, placebo, and no treatment; page not available) report a nocebo ratio of 0.90 and similar mean symptom scores during statin and placebo months. But the 90% is a ratio of symptom increases relative to no-tablet months, not a finding that 90% of all symptoms experienced while taking a statin also occurred while taking placebo. (LLM, conf=0.88)
Experimental — accuracy not yet measuredTen trials provided data on incidence of muscle symptoms.
“Ten trials [20,21,25,26,40,43,46–49] provided data on incidence of muscle symptoms”
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 [26]
The Methods (Participants) identify this as a statin crossover trial, and the Results (Participants) report that 36 of 60 participants had previously abandoned statins because of muscle ache. That is a pre-enrollment symptom history, not incidence of muscle symptoms during the trial; the reported trial outcomes concern symptom intensity of any type. This source also cannot establish the citing sentence’s total of ten trials. (LLM, conf=0.82)
Experimental — accuracy not yet measuredMost trials used statins with low to moderate intensity.
“Most trials used statins with low to moderate intensity [20,21,24–26,40,43,46,48,49]”
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 [26]
The Methods (Procedures and medications; page unavailable) state that this trial used atorvastatin 20 mg, and Study limitations say it tested one statin at one dose. The paper does not classify that dose by intensity or establish what most trials used; it supports the claim only as an example of a trial using that dose. (LLM, conf=0.83)
Experimental — accuracy not yet measuredNine trials provided data for treatment discontinuation due to muscle symptoms.
“Nine trials [22,25,26,40,43,46–48] provided data for treatment discontinuation due to muscle symptoms”
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 [26]
The Results section ('Early stopping of tablet months caused by intolerable symptoms'; page unavailable) reports early tablet stopping for statin and placebo, so this trial provided discontinuation data. But stopping was recorded for intolerable symptoms generally, not specifically for muscle symptoms. This paper also cannot establish the citing sentence’s aggregate count of nine trials. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe trials comparing statin-based therapy to placebo showed similar between-group incidence of muscle symptoms and statin-discontinuation rate.
“The trials comparing statin-based therapy to placebo showed similar between-group incidence of muscle symptoms and statin-discontinuation rate. [20,21,25,26,43,47]”
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 [26]
The Abstract Results report similar overall symptom scores during statin and placebo months and no significant difference in stopping frequency. The Discussion gives early tablet-cessation rates of 21.6% and 17.2%, respectively. The paper does not report a separate between-treatment incidence of muscle symptoms; it compares overall symptom scores, so that specific part of the claim is not established. (LLM, conf=0.86)
Experimental — accuracy not yet measured
The SAMSON trial showed that most statin-associated myalgias are due to the nocebo effect.
“In the context of statin-associated myalgias, it is important to consider the findings of the SAMSON trial, which elegantly showed that most statin-associated myalgias are due to the nocebo effect [18].”
From The Clinical Efficacy and Safety of Bempedoic Acid in Patients at Elevated Risk of Cardiovascular Disease: A Meta-Analysis of Randomized Clinical Trials (2024) · cites this paper as [18]
The Abstract Conclusions and Discussion say that most symptoms attributed to statin tablets in SAMSON were nocebo, with similar symptom scores on statin and placebo. The Results (Participants) say muscle ache was the most common reason for prior statin abandonment, but the reported nocebo finding concerns symptoms overall, not myalgias specifically; the trial also enrolled people who had abandoned statins because of symptoms. (LLM, conf=0.83)
Experimental — accuracy not yet measuredA large proportion of symptoms experienced while taking statins is attributable to the expectation of symptoms (the nocebo effect) rather than true pharmacological effects.
“Current evidence suggests that a large proportion of symptoms when on statins is secondary to the expectation of symptoms rather than true symptoms.”
From Intolerance upon statin rechallenge: A systematic review and meta-analysis of randomized controlled trials (2023) · cites this paper as [5]
23 studies were included for data extraction, with 9 RCTs analyzed quantitatively.
“23 studies were included for data extraction [20–26,35–50], with 9 RCTs analyzed quantitatively.”
New evidence on the management of SAMS has become available from randomized controlled trials and observational data.
“New evidence on the management of SAMS have since become available both from randomized control trials (RCTs) and from observational data [20–26].”
8 out of 13 RCTs were judged at low risk of bias.
“We judged 8 [20,22,23,25,26,40,48,49] out of 13 RCTs at low risk of bias (S2 File).”
13 RCTs conducted between 2006-2023 were included, of which five were parallel, five crossover, and three n-of-1.
“We included 13 RCTs conducted between 2006–2023, of which five were parallel RCTs [40,46–49], five were crossover RCTs [20,21,23,26,43] and three were n-of-1 RCTs [22,24,25] (S4 File, Table 1).”
Nine trials assessed statin against placebo.
“nine trials assessed statin against placebo [20–26,43]”
Two trials used symptom intensity expressed as a nocebo ratio.
“two trials [24,26] used symptom intensity expressed as a nocebo ratio”
With suggestion of a nocebo effect, trials started reporting the nocebo ratio.
“With suggestion of a nocebo effect, trials started reporting the nocebo ratio, e.g., the symptom intensity in placebo periods in relation to the symptom intensity when taking a statin [24,26].”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
<b>mice</b>: Multivariate Imputation by Chained Equations in<i>R</i>
Buuren, S. V., & Groothuis-Oudshoorn, K. (2011) · Journal of Statistical Software · doi:10.18637/jss.v045.i03 · Cited by 13,870 · see citing works
Mach, F., Baigent, C., Catapano, A. L., Koskinas, K. C., Casula, M., Badimon, L., Chapman, M. J., De Backer, G. G., Delgado, V., Ference, B. A., et al. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz455 · Cited by 8,961 · see citing works
Mach, F., Baigent, C., Catapano, A. L., Koskinas, K. C., Casula, M., Badimon, L., Chapman, M. J., De Backer, G. G., Delgado, V., Ference, B. A., et al. (2019) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2019.08.014 · Cited by 4,854 · see citing works
Sufficient Sample Sizes for Multilevel Modeling
Maas, C. J. M., & Hox, J. J. (2005) · Methodology · doi:10.1027/1614-2241.1.3.86 · Cited by 3,582 · see citing works
Collaborators, C. T. T. (. (2012) · The Lancet · doi:10.1016/s0140-6736(12)60367-5 · Cited by 2,833 · see citing works
Stroes, E. S., Thompson, P. D., Corsini, A., Vladutiu, G. D., Raal, F. J., Ray, K. K., Roden, M., Stein, E., Tokgözoğlu, L., Nordestgaard, B. G., et al. (2015) · European Heart Journal · doi:10.1093/eurheartj/ehv043 · Cited by 1,443 · see citing works
When words are painful: unraveling the mechanisms of the nocebo effect
Benedetti, F., Lanotte, M., Lopiano, L., & Colloca, L. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.02.020 · Cited by 636 · see citing works
Vickers, A. J. (2001) · BMC Medical Research Methodology · doi:10.1186/1471-2288-1-6 · Cited by 564 · see citing works
Nissen, S. E., Stroes, E., Dent-Acosta, R. E., Rosenson, R. S., Lehman, S. J., Sattar, N., Preiss, D., Bruckert, E., Ceška, R., Lepor, N., et al. (2016) · JAMA · doi:10.1001/jama.2016.3608 · Cited by 522 · see citing works
Effect of statins on skeletal muscle function
Parker, B. A., Capizzi, J. A., Grimaldi, A. S., Clarkson, P. M., Cole, S. M., Keadle, J., Chipkin, S., Pescatello, L. S., Simpson, K., White, C. M., et al. (2013) · Circulation · doi:10.1161/circulationaha.112.136101 · Cited by 500 · see citing works
The Nocebo Effect and Its Relevance for Clinical Practice
Colloca, L., & Miller, F. G. (2011) · Psychosomatic Medicine · doi:10.1097/psy.0b013e3182294a50 · Cited by 431 · see citing works
Gupta, A., Thompson, D., Whitehouse, A., Collier, T., Dahlof, B., Poulter, N., Collins, R., & Sever, P. (2017) · The Lancet · doi:10.1016/s0140-6736(17)31075-9 · Cited by 343 · see citing works
Self-citationN-of-1 Trial of a Statin, Placebo, or No Treatment to Assess Side Effects
Wood, F. A., Howard, J. P., Finegold, J. A., Nowbar, A. N., Thompson, D. M., Arnold, A. D., Rajkumar, C. A., Connolly, S., Cegla, J., Stride, C., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmc2031173 · Cited by 274 · see citing works
Self-citationFinegold, J. A., Manisty, C. H., Goldacre, B., Barron, A. J., & Francis, D. P. (2014) · European Journal of Preventive Cardiology · doi:10.1177/2047487314525531 · Cited by 214 · see citing works
Self-citationStatin treatment and muscle symptoms: series of randomised, placebo controlled n-of-1 trials
Herrett, E., Williamson, E., Brack, K., Beaumont, D., Perkins, A., Thayne, A., Shakur-Still, H., Roberts, I., Prowse, D., Goldacre, B., et al. (2021) · BMJ · doi:10.1136/bmj.n135 · Cited by 191 · see citing works
Barron, A., Zaman, N., Cole, G. D., Wensel, R., Okonko, D. O., & Francis, D. P. (2013) · International Journal of Cardiology · doi:10.1016/j.ijcard.2013.05.068 · Cited by 116 · see citing works
Self-citationToth, P. P., Granowitz, C. B., HULL, M. L., Anderson, A. J., & Philip, S. (2019) · Lipids in Health and Disease · doi:10.1186/s12944-019-1099-z · Cited by 89 · see citing works
Statins: Is It Really Time to Reassess Benefits and Risks?
Goldfine, A. B. (2012) · New England Journal of Medicine · doi:10.1056/nejmp1203020 · Cited by 82 · see citing works
Long term persistence with statin treatment in daily medical practice: Table 1
Mantel-Teeuwisse, A. K., Goettsch, W., Klungel, O. H., de Boer, A., & Herings, R. M. C. (2004) · Heart · doi:10.1136/hrt.2003.026187 · Cited by 74 · see citing works
Using evidence from different sources: an example using paracetamol 1000 mg plus codeine 60 mg
Smith, L. A., Moore, R. A., McQuay, H. J., & Gavaghan, D. (2001) · BMC Medical Research Methodology · doi:10.1186/1471-2288-1-1 · Cited by 60 · see citing works
Statin Intolerance: the Clinician’s Perspective
Štulc, T., Češka, R., & Gotto, A. M. (2015) · Current Atherosclerosis Reports · doi:10.1007/s11883-015-0552-3 · Cited by 59 · see citing works
Statin Denial: An Internet-Driven Cult With Deadly Consequences
Nissen, S. E. (2017) · Annals of Internal Medicine · doi:10.7326/m17-1566 · Cited by 50 · see citing works
Statin Denial: An Internet-Driven Cult With Deadly Consequences
Nissen, S. E. (2018) · Annals of Internal Medicine · doi:10.7326/l17-0626 · Cited by 27 · see citing works
Statin intolerance: the clinician’s perspective
Štulc, T., Češka, R., & Gotto, A. M. (2016) · Ukrainian Journal of Cardiology · Cited by 12 · see citing works
Toth, P. P., Granowitz, C. B., HULL, M. L., & Philip, S. (2019) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(19)32350-2 · Cited by 2 · see citing works
Flagged first, then by citations
1 of the 26 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Virani, S. S., Newby, L. K., Arnold, S. V., Bittner, V., Brewer, L. C., Demeter, S. H., Dixon, D. L., Fearon, W. F., Hess, B., Johnson, H. M., et al. (2023) · Circulation · doi:10.1161/cir.0000000000001168 · Cited by 1,598 · see citing works
Virani, S. S., Newby, L. K., Arnold, S. V., Bittner, V., Brewer, L. C., Demeter, S. H., Dixon, D. L., Fearon, W. F., Hess, B., Johnson, H. M., et al. (2023) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2023.04.003 · Cited by 596 · see citing works
Duan, Y., Gong, K., Xu, S., Zhang, F., Meng, X., & Han, J. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01125-5 · Cited by 538 · see citing works
The Lancet Commission on rethinking coronary artery disease: moving from ischaemia to atheroma
Zaman, S. J., Wasfy, J. H., Kapil, V., Ziaeian, B., Parsonage, W. A., Sriswasdi, S., Chico, T., Capodanno, D., Colleran, R., Sutton, N. R., et al. (2025) · The Lancet · doi:10.1016/s0140-6736(25)00055-8 · Cited by 228 · see citing works
Ruscica, M., Ferri, N., Banach, M., Sirtori, C. R., & Corsini, A. (2022) · Cardiovascular Research · doi:10.1093/cvr/cvac020 · Cited by 208 · see citing works
Cheeley, M. K., Saseen, J. J., Agarwala, A., Ravilla, S., Ciffone, N., Jacobson, T. A., Dixon, D. L., & Maki, K. C. (2022) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2022.05.068 · Cited by 197 · see citing works
Understanding the molecular mechanisms of statin pleiotropic effects
German, C. A., & Liao, J. K. (2023) · Archives of Toxicology · doi:10.1007/s00204-023-03492-6 · Cited by 154 · see citing works
Ten things to know about ten cardiovascular disease risk factors – 2022
Bays, H. E., Agarwala, A., German, C. A., Satish, P., Iluyomade, A., Dudum, R., Thakkar, A., Rifai, M. A., Mehta, A., Thobani, A., et al. (2022) · American Journal of Preventive Cardiology · doi:10.1016/j.ajpc.2022.100342 · Cited by 136 · see citing works
Warden, B. A., Guyton, J. R., Kovacs, A. C., Durham, J. A., Jones, L. K., Dixon, D. L., Jacobson, T. A., & Duell, P. B. (2023) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2022.09.001 · Cited by 111 · see citing works
Novel and future lipid-modulating therapies for the prevention of cardiovascular disease
Brandts, J., & Ray, K. K. (2023) · Nature Reviews Cardiology · doi:10.1038/s41569-023-00860-8 · Cited by 107 · see citing works
Goldstein, L. B., Toth, P. P., Dearborn, J. L., Giugliano, R. P., Hirsh, B. J., Peña, J. M., Selim, M. H., & Woo, D. (2023) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atv.0000000000000164 · Cited by 95 · see citing works
Joseph, J., Pajewski, N. M., Dolor, R. J., Sellers, M. A., Perdue, L., Peeples, S. R., Henrie, A. M., Woolard, N., Jones, W. S., Benziger, C. P., et al. (2023) · Journal of the American Geriatrics Society · doi:10.1111/jgs.18312 · Cited by 90 · see citing works
Hao, Q., Aertgeerts, B., Guyatt, G. H., Bekkering, G. E., Vandvik, P. O., Khan, S. U., Rodondi, N., Jackson, R., Reny, J., Al‐Ansary, L. A., et al. (2022) · BMJ · doi:10.1136/bmj-2021-069066 · Cited by 76 · see citing works
Lee, Y., Cho, J. Y., You, S. C., Lee, Y., Yun, K. H., Cho, Y., Shin, W., Im, S. W., Kang, W. C., Park, Y., et al. (2022) · European Heart Journal · doi:10.1093/eurheartj/ehac709 · Cited by 59 · see citing works
Contemporary Management of Dyslipidemia
Ferraro, R., Leucker, T. M., Martin, S. S., Banach, M., Jones, S. R., & Toth, P. P. (2022) · Drugs · doi:10.1007/s40265-022-01691-6 · Cited by 56 · see citing works
Functional Foods in Clinical Trials and Future Research Directions
Hajzer, Z. E., Alibrahem, W., Helu, N. K., Oláh, C., & Prokisch, J. (2025) · Foods · doi:10.3390/foods14152675 · Cited by 51 · see citing works
Gunta, S. P., O’Keefe, J. H., O’Keefe, E. L., & Lavie, C. J. (2023) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2023.02.007 · Cited by 42 · see citing works
Chin, Y. H., Ng, C. H., Chew, N., Kong, G., Lim, W. H., Tan, D. J. H., Chan, K. E., Tang, A. S. P., Huang, D. Q., Chan, M. Y., et al. (2022) · EClinicalMedicine · doi:10.1016/j.eclinm.2022.101685 · Cited by 41 · see citing works
Chin, Y. H., Lim, O. Z.-H., Lin, C., Chan, Y. Y., Kong, G., Ng, C. H., Chong, B., Syn, N. L. X., Chan, K. E., Muthiah, M. D., et al. (2022) · European Heart Journal - Quality of Care and Clinical Outcomes · doi:10.1093/ehjqcco/qcac060 · Cited by 40 · see citing works
Sex differences in LDL-C control in a primary care population: The PORTRAIT-DYS study
Gavina, C., Araujo, F. P., Teixeira, C. A. C., Ruivo, J., Corte-Real, A. L., Duarte, L. L., Canelas‐Pais, M., & Taveira‐Gomes, T. (2023) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2023.05.017 · Cited by 36 · see citing works
Ballard‐Hernandez, J., & Sall, J. (2023) · Nursing Clinics of North America · doi:10.1016/j.cnur.2023.05.002 · Cited by 36 · see citing works
Ng, C. H., Tang, A. S. P., Xiao, J., Wong, Z. Y., Yong, J. N., Fu, C. E., Zeng, R. W., Tan, C., Wong, G. H. Z., Teng, M. L. P., et al. (2023) · Hepatology Communications · doi:10.1097/hc9.0000000000000005 · Cited by 35 · see citing works
Placebo: a brief updated review
Pardo-Cabello, A. J., Manzano‐Gamero, V., & Puche-Cañas, E. (2022) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-022-02280-w · Cited by 32 · see citing works
D’Amario, D., Laborante, R., Bianchini, E., Galli, M., Ciliberti, G., Mennuni, M. G., & Patti, G. (2023) · International Journal of Cardiology · doi:10.1016/j.ijcard.2023.131219 · Cited by 29 · see citing works
Mansfield, B. S., Mohamed, F., Larouche, M., & Raal, F. J. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13144160 · Cited by 28 · see citing works
Landscape of Statin as a Cornerstone in Atherosclerotic Cardiovascular Disease
Yang, C., Wu, Y., Qian, J., & Li, J. (2023) · Reviews in Cardiovascular Medicine · doi:10.31083/j.rcm2412373 · Cited by 27 · see citing works
New insights into the role of bempedoic acid and ezetimibe in the treatment of hypercholesterolemia
Pirillo, A., & Catapano, A. L. (2022) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000706 · Cited by 25 · see citing works
SAMSON and the Nocebo Effect: Management of Statin Intolerance
Krishnamurthy, A., Bradley, C., Ascunce, R. R., & Kim, S. M. (2022) · Current Cardiology Reports · doi:10.1007/s11886-022-01729-x · Cited by 24 · see citing works
Statin associated muscle symptoms (SAMS): strategies for prevention, assessment and management
Iatan, I., Mancini, G. B. J., Yeoh, E., & Hegele, R. A. (2023) · Expert Review of Cardiovascular Therapy · doi:10.1080/14779072.2023.2215982 · Cited by 24 · see citing works
Shah, M., Shrestha, K., Tseng, C., Goyal, A., Liewluck, T., & Gupta, L. (2024) · International Journal of Rheumatic Diseases · doi:10.1111/1756-185x.15337 · Cited by 23 · see citing works
Statin-related Muscle Toxicity: An Evidence-based Review
Jeeyavudeen, M. S., Pappachan, J. M., & Arunagirinathan, G. (2022) · touchREVIEWS in Endocrinology · doi:10.17925/ee.2022.18.2.89 · Cited by 21 · see citing works
Statins and non-alcoholic fatty liver disease: A concise review
Pereira, E. N. G. D. S., Franco, R. L. C., dos Santos, R. D. C., & Daliry, A. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117805 · Cited by 21 · see citing works
Targeting PCSK9 With Antibodies and Gene Silencing to Reduce LDL Cholesterol
Newman, C. B., & Tobert, J. A. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgac708 · Cited by 20 · see citing works
Bittner, V., Linnebur, S. A., Dixon, D. L., Forman, D. E., Green, A. R., Jacobson, T. A., Orkaby, A. R., Saseen, J. J., & Virani, S. S. (2025) · Journal of clinical lipidology · doi:10.1016/j.jacl.2024.09.005 · Cited by 20 · see citing works
Sayed, A., Shazly, O., Slipczuk, L., Krittanawong, C., Baloch, F., & Virani, S. S. (2024) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-023-07474-9 · Cited by 19 · see citing works
“In the context of statin-associated myalgias, it is important to consider the findings of the SAMSON trial, which elegantly showed that most statin-associated myalgias are due to the nocebo effect [ 18].”
Zimerman, A., Kunzler, A. L. F., Weber, B., Ran, X., Murphy, S. A., Wang, H., Honarpour, N., KEECH, A. C., Sever, P. S., Sabatine, M. S., et al. (2025) · Circulation · doi:10.1161/circulationaha.124.072756 · Cited by 19 · see citing works
Self-citationN-of-1 trials: The epitome of personalized medicine?
Samuel, J. P., Wootton, S. H., & Tyson, J. E. (2023) · Journal of Clinical and Translational Science · doi:10.1017/cts.2023.583 · Cited by 19 · see citing works
Quality of life in patients with statin intolerance: a multicentre prospective registry study
Stürzebecher, P. E., Gouni‐Berthold, I., Mateev, C., Frenzel, O., Erbe, S., Boeckel, J., Scholz, M. R., Schatz, U., Weingärtner, O., Kassner, U., et al. (2024) · The Lancet Regional Health - Europe · doi:10.1016/j.lanepe.2024.100981 · Cited by 19 · see citing works
Lipid Lowering Therapy Utilization and Lipid Goal Attainment in Women
van Oortmerssen, J. A. E., Mulder, J. W. C. M., van der Bijl, M. F., Mijnster, R. J. M., Kavousi, M., & van Lennep, J. E. R. (2025) · Current Atherosclerosis Reports · doi:10.1007/s11883-025-01275-1 · Cited by 18 · see citing works
Statin‐associated muscle symptoms—A review: Individualizing the approach to optimize care
Wiggins, B. S., Backes, J. M., & Hilleman, D. (2022) · Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/phar.2681 · Cited by 17 · see citing works
Mutschlechner, D., Tscharre, M., Huber, K., & Gremmel, T. (2023) · European Heart Journal - Cardiovascular Pharmacotherapy · doi:10.1093/ehjcvp/pvad052 · Cited by 17 · see citing works
Bempedoic Acid: Lipid Lowering for Cardiovascular Disease Prevention
Albosta, M. S., Grant, J. K., & Michos, E. D. (2023) · Heart International · doi:10.17925/hi.2023.17.2.1 · Cited by 16 · see citing works
Bittner, V., Linnebur, S. A., Dixon, D. L., Forman, D. E., Green, A. R., Jacobson, T. A., Orkaby, A. R., Saseen, J. J., & Virani, S. S. (2025) · Journal of the American Geriatrics Society · doi:10.1111/jgs.19398 · Cited by 15 · see citing works
Awad, I. A., Alcazar‐Félix, R. J., Stadnik, A., Kinkade, S., Jhaveri, A., Lee, J. C., Hage, S. F., Iqbal, J., Polster, S. P., Shenkar, R., et al. (2025) · The Lancet Neurology · doi:10.1016/s1474-4422(25)00036-5 · Cited by 14 · see citing works
Red yeast rice: a functional food used to reduce hyperlipidemia
Fan, X., Han, J., Zhang, F., & Chen, W. (2022) · Food Reviews International · doi:10.1080/87559129.2022.2043894 · Cited by 14 · see citing works
Mitkowski, P. P., Witkowski, A., Stępińska, J., Banach, M., Jankowski, P., Gąsior, M., Wita, K., Bartuś, S., Burchardt, P., Farkowski, M. M., et al. (2023) · Kardiologia Polska · doi:10.33963/kp.a2023.0162 · Cited by 14 · see citing works
Comprehensive review of statin-intolerance and the practical application of Bempedoic Acid
Yarrarapu, S. N. S., Goyal, A., Venkata, V. S., Panchal, V. S., Sivasubramanian, B. P., Du, D. T., Jakulla, R. S., Pamulapati, H., Afaq, M. A., Owens, S., et al. (2024) · Journal of Cardiology · doi:10.1016/j.jjcc.2024.03.006 · Cited by 14 · see citing works
Sheth, S., Banach, M., & Toth, P. P. (2024) · Expert Review of Cardiovascular Therapy · doi:10.1080/14779072.2024.2398444 · Cited by 14 · see citing works
Khouri, C., Larabi, A., Verger, P., Gauna, F., Cracowski, J., & Ward, J. K. (2022) · Drug Safety · doi:10.1007/s40264-022-01220-0 · Cited by 14 · see citing works
Bempedoic acid: new evidence and recommendations on use
Paponja, K., Pećin, I., Reiner, Ž., & Banach, M. (2023) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000911 · Cited by 13 · see citing works
Effects of a stepwise, structured LDL-C lowering strategy in patients post-acute coronary syndrome
Khader, A. O., Trier, T. J. V., van der Brug, S., Liem, A. H., Groenemeijer, B. E., Schut, A., Jorstad, H. T., Martens, F. M. A. C., & Alings, M. (2024) · Netherlands Heart Journal · doi:10.1007/s12471-023-01851-7 · Cited by 13 · see citing works
Chinese Expert Consensus on the Clinical Diagnosis and Management of Statin Intolerance
Li, J., Dou, K., Zhou, Z., Zhao, D. H., Ye, P., Chen, H., Chen, Z., Peng, D., Guo, Y., Wu, N., et al. (2024) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.3213 · Cited by 13 · see citing works
Cholesterol Lowering in Older Adults: Should We Wait for Further Evidence?
Jamil, Y., Cohen, R., Alameddine, D., Deo, S. V., Kumar, M., & Orkaby, A. R. (2024) · Current Atherosclerosis Reports · doi:10.1007/s11883-024-01224-4 · Cited by 13 · see citing works
Recent progress in gene therapy for familial hypercholesterolemia treatment
Luo, Y., Hou, Y., Zhao, W., & Yang, B. (2024) · iScience · doi:10.1016/j.isci.2024.110641 · Cited by 13 · see citing works
Benefits and limitations of statin use in primary cardiovascular prevention: recent advances
Strandberg, T. E. (2022) · Polskie Archiwum Medycyny Wewnętrznej · doi:10.20452/pamw.16258 · Cited by 13 · see citing works
Pharmacotherapy in familial hypercholesterolemia - Current state and emerging paradigms
Kallapur, A. S., & Sallam, T. (2021) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2021.12.011 · Cited by 13 · see citing works
Cha, J., Hong, S. J., Kim, J. H., Lim, S., Joo, H. J., Park, J. H., Yu, C. W., Lee, P. H., Lee, S., Lee, C. W., et al. (2023) · American Heart Journal · doi:10.1016/j.ahj.2023.03.002 · Cited by 12 · see citing works
Tay, P. W. L., Ng, C. H., Lin, S. Y., Chin, Y. H., Xiao, J., Lim, W. H., Lim, S. Y., Fu, C. E., Chan, K. E., Quek, J., et al. (2022) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000002042 · Cited by 12 · see citing works
Benefits of Bempedoic Acid — Clearer Now
Alexander, J. H. (2023) · New England Journal of Medicine · doi:10.1056/nejme2301490 · Cited by 12 · see citing works
Statin-Associated Muscle Symptoms: Identification and Recommendations for Management
Maki, K. C., Kirkpatrick, C. F., Cheeley, M. K., & Jacobson, T. A. (2024) · Current Atherosclerosis Reports · doi:10.1007/s11883-024-01246-y · Cited by 11 · see citing works
Cha, J., Kim, J. H., Hong, S. J., Lim, S., Joo, H. J., Park, J. H., Yu, C. W., Lee, P. H., Lee, S., Lee, C. W., et al. (2024) · Journal of Internal Medicine · doi:10.1111/joim.20029 · Cited by 10 · see citing works
Laufs, U., Lincoff, A. M., Nicholls, S. J., Li, N., Bloedon, L. T., Sasiela, W. J., Powell, H. A., Herout, P. M., Thompson, P. D., & Nissen, S. E. (2024) · Journal of clinical lipidology · doi:10.1016/j.jacl.2024.12.014 · Cited by 10 · see citing works
Kytö, V., Saraste, A., & Tornio, A. (2022) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2022.06.1019 · Cited by 10 · see citing works
The Relevance Of Real-World Data For The Evaluation Of Neuropathic Pain Treatments
Baron, R., Mick, G., & Serpell, M. G. (2022) · Pain Management · doi:10.2217/pmt-2022-0057 · Cited by 10 · see citing works
Sabouret, P. F., Puymirat, É., Kownator, S., ABDENNBI, K., LEBEAU, F., MELTZ, M., Angoulvant, D., & Schiele, F. (2022) · Panminerva Medica · doi:10.23736/s0031-0808.22.04777-2 · Cited by 10 · see citing works
That Myalgia of Yours Is Not From Statin Intolerance
Toth, P. P. (2021) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2021.07.025 · Cited by 10 · see citing works
A closed-loop cholesterol shunt controlling experimental dyslipidemia
Unal, G., Xie, Y., & Fussenegger, M. (2025) · Cell Metabolism · doi:10.1016/j.cmet.2025.08.011 · Cited by 9 · see citing works
Parhofer, K. G., Anastassopoulou, A., Calver, H., Becker, C., Rathore, A., Dave, R., & Zamfir, C. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12020705 · Cited by 9 · see citing works
Orhon, P., Robert, M., Bernardeau, C., Hlavaty, A., Fusaroli, M., Roustit, M., Cracowski, J., & Khouri, C. (2023) · BioDrugs · doi:10.1007/s40259-023-00603-8 · Cited by 9 · see citing works
Karalis, D. G. (2023) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000896 · Cited by 9 · see citing works
Apple, S. J., Clark, R. E., Daich, J., González, M. L., Ostfeld, R. J., Toth, P. P., Bittner, V., Martin, S. S., Rana, J. S., Nasir, K., et al. (2023) · Reviews in Cardiovascular Medicine · doi:10.31083/j.rcm2412350 · Cited by 9 · see citing works
Derobertmasure, A., Toh, L. S., Wotring, V. E., Williams, P. M., Morbidelli, L., Stingl, J., Vinken, M., Ramadan, R., Chhun, S., & Boutouyrie, P. (2025) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2025.107063 · Cited by 8 · see citing works
Adverse Effects and Treatment Discontinuation of Blood Pressure–Lowering Drugs and Combinations
Wang, N., van der Hoorn, S., Pant, R., Kumar, A., Dhurjatic, R., Haghdoost, F., Abhayaratna, C., Egan, B. M., Schutte, A. E., Berwanger, O., et al. (2026) · JAMA · doi:10.1001/jama.2026.6214 · Cited by 8 · see citing works
Guthrie, B., Rogers, G., Livingstone, S. J., Morales, D. R., Donnan, P. T., Davis, S., Youn, J.-H., Hainsworth, R., Thompson, A., & Payne, K. (2024) · Health and Social Care Delivery Research · doi:10.3310/kltr7714 · Cited by 8 · see citing works
Walker, A. J., Zhu, J., Thoma, F. W., Marroquin, O. C., Makani, A., Gulati, M., Gianos, E., Virani, S. S., Rodríguez, F., Reís, S. E., et al. (2024) · American Journal of Preventive Cardiology · doi:10.1016/j.ajpc.2024.100664 · Cited by 8 · see citing works
Wettermark, B., Kalantaripour, C., Forslund, T., & Hjemdahl, P. (2024) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-024-03724-3 · Cited by 8 · see citing works
Søgaard, M., Skjøth, F., Behrendt, C., Nicolajsen, C. W., Højen, A. A., Dahl, M., Petersen, C. N., & Ørskov, M. (2025) · European Journal of Vascular and Endovascular Surgery · doi:10.1016/j.ejvs.2025.09.015 · Cited by 8 · see citing works
Kravvariti, E., Kasdagli, M., Diomatari, K. M., Mouratidou, P., Daskalakis, K., Mitsikostas, D. D., Sfikakis, P. P., & Yavropoulou, M. P. (2023) · Osteoporosis International · doi:10.1007/s00198-022-06658-7 · Cited by 8 · see citing works
Identifying and Managing Those at Risk for Vaccine-Related Allergy and Anaphylaxis
Stone, C. A., Garvey, L. H., Nasser, S. M., Lever, C., Triggiani, M., Parente, R., & Phillips, E. J. (2023) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2023.05.004 · Cited by 8 · see citing works
Impact of statin withdrawal on perceived and objective muscle function
Peyrel, P., Mauriège, P., Frenette, J., Laflamme, N., Greffard, K., Dufresne, S. S., Huth, C., Bergeron, J., & Joanisse, D. R. (2023) · PLoS ONE · doi:10.1371/journal.pone.0281178 · Cited by 8 · see citing works
The role of atherogenic lipoproteins in diabetes: Molecular aspects and clinical significance
Banerjee, Y., Patti, A. M., Giglio, R. V., Ciaccio, M., Vichithran, S., Faisal, S., Stoian, A. P., Rizvi, A. A., & Rizzo, M. (2023) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2023.108517 · Cited by 8 · see citing works
Kraut, R., Wierenga, F., Molstad, E., Korownyk, C., Perry, D., Dennett, L., & Garrison, S. (2023) · PLOS ONE · doi:10.1371/journal.pone.0295857 · Cited by 7 · see citing works
Zhang, X., Wang, C., Min, R., Zhou, Q., Qi, Y., & Fan, J. (2024) · Nutrition Research · doi:10.1016/j.nutres.2024.03.002 · Cited by 7 · see citing works
Højen, A. A., Jacobsen, S., Nicolajsen, C. W., Eldrup, N., Petersen, C. N., Behrendt, C., Dahl, M., & Søgaard, M. (2025) · VASA · doi:10.1024/0301-1526/a001223 · Cited by 7 · see citing works
Mehta, A., Dixon, D. L., Saeed, A., Kelly, M. S., Gulati, M., Shapiro, M. D., Sperling, L. S., & Virani, S. S. (2023) · Current Cardiology Reports · doi:10.1007/s11886-023-01861-2 · Cited by 7 · see citing works
Sun, Y., Zhang, H., Liu, R., Xing, S., Huang, R., Di, D., Zhang, X., Zhu, B., & Wu, H. (2024) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2024.117715 · Cited by 7 · see citing works
Marquis‐Gravel, G., Bhatia, S., Brown, V., & Goodman, S. G. (2024) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2024.05.010 · Cited by 7 · see citing works
Defining, measuring, and addressing medication non-adherence in cardiovascular disease
Livori, A., Dalli, L. L., Nicholls, S. J., & Nelson, A. J. (2024) · Future Cardiology · doi:10.1080/14796678.2024.2433888 · Cited by 7 · see citing works
Cardiovascular disease — risk assessment and reduction: NICE 2023 update for GPs
Williams, E., Round, T., & Jones, N. R. (2024) · British Journal of General Practice · doi:10.3399/bjgp24x739905 · Cited by 6 · see citing works
Rheumatoid arthritis and cardiovascular risk: keep it simple and compassionate
Ausserwinkler, M., Neumann, H. J., & Wernly, B. (2023) · Rheumatology International · doi:10.1007/s00296-023-05333-2 · Cited by 6 · see citing works
Cultural influences on placebo and nocebo effects
Cundiff-O’Sullivan, R. L., Oula, D., Shafir, R., & Colloca, L. (2023) · Oxford University Press eBooks · doi:10.1093/med/9780197645444.003.0004 · Cited by 6 · see citing works
Patti, G., Cavallari, I., Cesaro, A., Gragnano, F., Riva, L., Fimiani, F., Cuccia, C., Fresco, C., Calabrò, P., Leonardi, S., et al. (2022) · Vascular Pharmacology · doi:10.1016/j.vph.2022.107137 · Cited by 6 · see citing works
Are statins making older persons weaker? A discontinuation study of muscular side effects
Korsholm, M. B., Pødenphanth, T. W., Strømgaard, S. K., Petersen, L. W., Alexandersen, C., Hoffmann, S. S., Rasmusen, H. K., Suetta, C., Pedersen, K. D., Pressel, E., et al. (2023) · GeroScience · doi:10.1007/s11357-023-00817-2 · Cited by 6 · see citing works
Treating Hypercholesterolemia in Older Adults for Primary Prevention of Cardiovascular Events
Al-Ani, A., Jamil, Y., & Orkaby, A. R. (2024) · Drugs & Aging · doi:10.1007/s40266-024-01139-4 · Cited by 6 · see citing works
Teo, C. B., Tan, P. Y., Tay, R. Y. K., Khoo, J. J. C., Watts, G. F., & Loh, W. J. (2022) · High Blood Pressure & Cardiovascular Prevention · doi:10.1007/s40292-022-00526-5 · Cited by 6 · see citing works
Pallarés‐Carratalá, V., Barrios, V., Fierro-González, D., García, J. P., & Cinza‐Sanjurjo, S. (2023) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph20032388 · Cited by 6 · see citing works
Solitano, V., Hogan, M., Singh, S. S., Danese, S., Peyrin‐Biroulet, L., Vuyyuru, S. K., MacDonald, J. K., Zou, G., Yuan, Y., Sands, B. E., et al. (2025) · Journal of Crohn s and Colitis · doi:10.1093/ecco-jcc/jjaf191 · Cited by 5 · see citing works
Mangone, L. A., Kwon, O. S., Johnson, B. T., Wu, Y., & Pescatello, L. S. (2024) · Mayo Clinic Proceedings Innovations Quality & Outcomes · doi:10.1016/j.mayocpiqo.2024.01.003 · Cited by 5 · see citing works
Pharmacological Profile and Mechanisms of Cardiovascular Protective Effects of Statins: An Update
Elhwuegi, A. S., & Elfakhri, M. (2025) · Libyan International Medical University Journal · doi:10.1055/s-0045-1809043 · Cited by 5 · see citing works
Statinintoleranz und statinassoziierte Muskelschmerzen
Stürzebecher, P. E., Schumann, F., Kassner, U., & Laufs, U. (2022) · Herz · doi:10.1007/s00059-022-05114-w · Cited by 5 · see citing works
- Authors
- Howard, J. P., Wood, F. A., Finegold, J. A., Nowbar, A. N., Thompson, D. M., Arnold, A. D., Rajkumar, C. A., Connolly, S., Cegla, J., Stride, C., Sever, P., Norton, C., Thom, S. A. M., Shun-Shin, M. J., & Francis, D. P.
- Affiliations
- Imperial College London (GB)
- Imperial College Healthcare NHS Trust (GB)
- University of Sheffield (GB)
- King's College London (GB)
- ORCID
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2021-09
- Volume
- 78
- Issue
- 12
- Pages
- 1210-1222
- ISSN
- 0735-1097 (ISSN-L)
- PMC
- PMC8453640
- OpenAlex
- W3200521827
- Cited by
- 198
- References
- 26
- Citations by year
- 2026: 35 · 2025: 34 · 2024: 38 · 2023: 51 · 2022: 38 · 2021: 2
- FWCI
- 30.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Spiral (Imperial College London) (submittedVersion, other-oa)
- Funders
- Wellcome Trust (212183/Z/18/Z)
- National Institute for Health and Care Research (CL-2020-21-004, NIHR300166, CL-2018-21-001)
- British Heart Foundation (PG/15/7/31235, FS/14/25/30676, FS/14/27/30752)
- Medical Research Council (MR/S021108/1)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Keywords
- statins, atorvastatin, statin adverse effects, nocebo effect, placebo effect, symptom intensity, crossover trial, daily symptom monitoring, mobile health apps, hypercholesterolemia
- MeSH terms
- Atorvastatin, Aged, Double-Blind Method, Female, Humans, Male, Middle Aged, Cross-Over Studies, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Nocebo Effect
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
