Online first
Review paper
Published online: 2024-05-02
Navigating patient reluctance to statin intolerance
Pubmed: 38712783
Abstract
Statin therapy is a cornerstone in the management of dyslipidemia, both in primary and secondary prevention of cardiovascular events. Despite strong guidelines supporting statin use, concerns regarding side effects, particularly musculoskeletal symptoms, contribute to statin intolerance and patient reluctance. While statin intolerance is reported in 5% to 30% of patients, its true prevalence may be overestimated due to the influence of the nocebo effect. Factors associated with higher incidence of statin intolerance include older age, female gender, comorbidities such as diabetes and chronic kidney disease, and concurrent use of medications such as antiarrhythmic agents or calcium channel blockers. Clinical characterization of statin intolerance requires thorough evaluation and exclusion of alternative causes of musculoskeletal symptoms. Strategies to address statin intolerance include reassessing cardiovascular risk, engaging in shared decision-making, statin rechallenge after appropriate washout periods, dosage titration for tolerability, and consideration of alternative therapies when LDL goals cannot be achieved with statins. This review provides an overview of the spectrum of statin intolerance, its clinical assessment, and a systematic approach to caring for a patient with statin intolerance.
References
- Lloyd-Jones DM, Morris PB, Ballantyne CM, et al. 2022 ACC expert consensus decision pathway on the role of nonstatin therapies for ldl-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2022; 80(14): 1366–1418.
- Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). Eur Heart J. 2020; 41(1): 111–188.
- SCORE2 working group, ESC Cardiovascular risk collaboration. SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe. Eur Heart J. 2021; 42(25): 2439–54.
- Mitkowski P, Witkowski A, Stępińska J, et al. Position of the Polish Cardiac Society on therapeutic targets for LDL cholesterol concentrations in secondary prevention of myocardial infarctions. Kardiol Pol. 2023; 81(7-8): 818–823.
- Rallidis LS, Tsamoulis D, Leventis I, et al. Extremely high-risk patients with acute coronary syndrome: How "extreme" should lipid-lowering therapy be if the LDL-C target <40 mg/dl is considered? Kardiol Pol. 2023; 81(10): 1012–1014.
- Stein LH, Berger J, Tranquilli M, et al. Effect of statin drugs on thoracic aortic aneurysms. Am J Cardiol. 2013; 112(8): 1240–1245.
- Golder Su, Weissenbacher D, O'Connor K, et al. Patient-reported reasons for switching or discontinuing statin therapy: A mixed methods study using social media. Drug Saf. 2022; 45(9): 971–981.
- Bradley CK, Wang TY, Li S, et al. Patient-Reported reasons for declining or discontinuing statin therapy: Insights from the PALM registry. J Am Heart Assoc. 2019; 8(7): e011765.
- Jacobson TA, Cheeley MK, Jones PH, et al. The statin adverse treatment experience survey: Experience of patients reporting side effects of statin therapy. J Clin Lipidol. 2019; 13(3): 415–424.
- Rosenbaum D, Dallongeville J, Sabouret P, et al. Discontinuation of statin therapy due to muscular side effects: a survey in real life. Nutr Metab Cardiovasc Dis. 2013; 23(9): 871–875.
- Cheeley MK, Saseen JJ, Agarwala A, et al. NLA scientific statement on statin intolerance: a new definition and key considerations for ASCVD risk reduction in the statin intolerant patient. J Clin Lipidol. 2022; 16(4): 361–375.
- Fitchett DH, Hegele RA, Verma S. Cardiology patient page. Statin intolerance. Circulation. 2015; 131(13): e389–e391.
- Gaine SP, Kulkarni A, Dixon DL, Patel J. NLA 2022 Definition of Statin Intolerance. 2022.
- Newman CB, Preiss D, Tobert JA, et al. Statin safety and associated adverse events: A scientific statement from the American Heart Association. Arterioscler Thromb Vasc Biol. 2019; 39(2): e38–e81.
- Bytyçi I, Penson PE, Mikhailidis DP, et al. Prevalence of statin intolerance: A meta-analysis. Eur Heart J. 2022; 43(34): 3213–3223.
- Meza-Contreras A, Wenczenovicz C, Ruiz-Arellanos K, et al. Statin intolerance management: A systematic review. Endocrine. 2023; 79(3): 430–436.
- Polaczyk M, Olszanecka A, Wojciechowska W, et al. Multiple drug intolerance in patients with arterial hypertension: prevalence and determining factors. Pol Arch Intern Med. 2023; 133(3).
- Krishnamurthy A, Bradley C, Ascunce R, et al. SAMSON and the nocebo effect: Management of statin intolerance. Curr Cardiol Rep. 2022; 24(9): 1101–1108.
- Moon J, Cohen Sedgh R, Jackevicius CA. Examining the nocebo effect of statins through statin adverse events reported in the Food and Drug Administration adverse event reporting system. Circ Cardiovasc Qual Outcomes. 2021; 14(1): e007480.
- Blasini M, Corsi N, Klinger R, et al. Nocebo and pain: An overview of the psychoneurobiological mechanisms. Pain Rep. 2017; 2(2).
- Wartolowska K. The nocebo effect as a source of bias in the assessment of treatment effects. F1000Res. 2019; 8: 5.
- Penson PE, Banach M. Nocebo/drucebo effect in statin-intolerant patients: an attempt at recommendations. Eur Heart J. 2021; 42(47): 4787–4788.
- Nissen SE. Statin denial: An internet-driven cult with deadly consequences. Ann Intern Med. 2017; 167(4): 281–282.
- Penson PE, Mancini GB, Toth PP, et al. Introducing the 'Drucebo' effect in statin therapy: a systematic review of studies comparing reported rates of statin-associated muscle symptoms, under blinded and open-label conditions. J Cachexia Sarcopenia Muscle. 2018; 9(6): 1023–1033.
- Cardiology ACo. American College of Cardiology Statin Intolerance Tool. https://tools.acc.org/StatinIntolerance/?_ga=2.222956114.890717625.1704825019-1126116753.1704041760#!/ (accessed: March 20, 2024).
- Mayo Clinic. Statin Choice Decision Aid. https://statindecisionaid.mayoclinic.org/ (accessed: March 20, 2024).
- Choudhary A, Rawat U, Kumar P, et al. Pleotropic effects of statins: the dilemma of wider utilization of statin. Egypt Heart J. 2023; 75(1): 1.
- Oesterle A, Laufs U, Liao JK. Pleiotropic effects of statins on the cardiovascular system. Circ Res. 2017; 120(1): 229–243.
- Wasim R, Ansari TM, Ahsan F, et al. Pleiotropic benefits of statins in cardiovascular diseases. Drug Res (Stuttg). 2022; 72(9): 477–486.
- Link E, Parish S, Armitage J, et al. SLCO1B1 variants and statin-induced myopathy — a genomewide study. N Engl J Med. 2008; 359(8): 789–799.
- Stroes ES, Thompson PD, Corsini A, et al. Statin-associated muscle symptoms: impact on statin therapy — European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. Eur Heart J. 2015; 36(17): 1012–1022.
- Vassy JL, Gaziano JM, Green RC, et al. Effect of pharmacogenetic testing for statin myopathy risk vs usual care on blood cholesterol: A randomized clinical trial. JAMA Netw Open. 2020; 3(12): e2027092.
- Orringer CE, Grant JK, Tokgozoglu L. A review of statin intolerance: A focus on statin-attributed muscle symptoms. Curr Atheroscler Rep. 2022; 24(11): 839–847.
- ASCVD Risk Estimator. https://tools.acc.org/ascvd-risk-estimator/default.aspx (accessed: March 20, 2024).
- MESA Risk Score and Coronary Age Calculator. https://internal.mesa-nhlbi.org/about/procedures/tools/mesa-score-risk-calculator (accessed: March 20, 2024).
- Astro-CHARM. https://astrocharm.org/calculator-working/ (accessed: March 20, 2024).
- EPIC. https://www.epic.com/ (accessed: March 20, 2024).
- Gepner AD, Piper ME, Johnson HM, et al. Effects of smoking and smoking cessation on lipids and lipoproteins: outcomes from a randomized clinical trial. Am Heart J. 2011; 161(1): 145–151.
- Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019; 140(11): e596–e646.
- Liu Z, Tian Z, Zhao D, et al. Effects of coenzyme Q10 supplementation on lipid profiles in adults: A meta-analysis of randomized controlled trials. J Clin Endocrinol Metab. 2022; 108(1): 232–249.
- Ghodeshwar GK, Dube A, Khobragade D. Impact of lifestyle modifications on cardiovascular health: A narrative review. Cureus. 2023; 15(7): e42616.
- Ma ZY, Yang SP, Li Y, et al. Associations between the use of red yeast rice preparations and adverse health outcomes: An umbrella review of meta-analyses of randomized controlled trials. J Integr Med. 2024; 22(2): 126–136.
- Laffin LJ, Bruemmer D, Garcia M, et al. Comparative effects of low-dose rosuvastatin, placebo, and dietary supplements on lipids and inflammatory biomarkers. J Am Coll Cardiol. 2023; 81(1): 1–12.
- Reiner Z. Resistance and intolerance to statins. Nutr Metab Cardiovasc Dis. 2014; 24(10): 1057–1066.
- Banach M, Rizzo M, Toth PP, et al. Statin intolerance — an attempt at a unified definition. Position paper from an International Lipid Expert Panel. Arch Med Sci. 2015; 11(1): 1–23.
- Nicholls SJ. PCSK9 inhibitors and reduction in cardiovascular events: Current evidence and future perspectives. Kardiol Pol. 2023; 81(2): 115–122.
- Nissen SE, Menon V, Nicholls SJ, et al. Bempedoic acid and cardiovascular outcomes in statin-intolerant patients. N Engl J Med. 2023; 388(15): 1353–1364.
- Raschi E, Casula M, Cicero AFG, et al. Beyond statins: New pharmacological targets to decrease LDL-cholesterol and cardiovascular events. Pharmacol Ther. 2023; 250: 108507.
- Singh A, Cho LS. Nonstatin therapy to reduce low-density lipoprotein cholesterol and improve cardiovascular outcomes. Cleve Clin J Med. 2024; 91(1): 53–63.
- Anagnostis P, Antza C, Florentin M, et al. Familial hypercholesterolemia and its manifestations: Practical considerations for general practitioners. Kardiol Pol. 2023; 81(11): 1081–1088.
- Morrone D, Weintraub WS, Toth PP, et al. Lipid-altering efficacy of ezetimibe plus statin and statin monotherapy and identification of factors associated with treatment response: a pooled analysis of over 21,000 subjects from 27 clinical trials. Atherosclerosis. 2012; 223(2): 251–261.
