Cardiovasc Prev Pharmacother.  2022 Jan;4(1):1-6. 10.36011/cpp.2022.4.e4.

Adverse effects of statin therapy and their treatment

• Cheon DY
• Jo SH

• KMID: 2536926
• DOI: http://doi.org/10.36011/cpp.2022.4.e4

Abstract

Statins are one of the most widely used drugs worldwide as first-line drugs for the treatment of hyperlipidemia and the prevention and treatment of cardiovascular diseases. Most of the side effects of statins are known to be mild, and mainly hepatotoxicity and various muscle symptoms are known. Recently, there have been studies on concerns about an increase in the incidence of diabetes after using statins, but it was found that the benefits sufficiently outweigh the risk of side effects. Therefore, the use of statins in the appropriate group should be actively performed, and it seems that the side effects can be prevented through close physical observation and appropriate examination.

Keyword

Statin; Adverse effect

Reference

1. Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005; 366:1267–78.

2. Brugts JJ, Yetgin T, Hoeks SE, Gotto AM, Shepherd J, Westendorp RG, et al. The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials. BMJ. 2009; 338:b2376.

3. Thavendiranathan P, Bagai A, Brookhart MA, Choudhry NK. Primary prevention of cardiovascular diseases with statin therapy: a meta-analysis of randomized controlled trials. Arch Intern Med. 2006; 166:2307–13.

4. Alsheikh-Ali AA, Maddukuri PV, Han H, Karas RH. Effect of the magnitude of lipid lowering on risk of elevated liver enzymes, rhabdomyolysis, and cancer: insights from large randomized statin trials. J Am Coll Cardiol. 2007; 50:409–18.

5. Hippisley-Cox J, Coupland C. Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ. 2010; 340:c2197.

6. Kashani A, Phillips CO, Foody JM, Wang Y, Mangalmurti S, Ko DT, et al. Risks associated with statin therapy: a systematic overview of randomized clinical trials. Circulation. 2006; 114:2788–97.

7. Kostis JB, Dobrzynski JM. Statin use and cataract. JAMA Ophthalmol. 2014; 132:363–4.

8. Mach F, Ray KK, Wiklund O, Corsini A, Catapano AL, Bruckert E, et al. Adverse effects of statin therapy: perception vs. the evidence: focus on glucose homeostasis, cognitive, renal and hepatic function, haemorrhagic stroke and cataract. Eur Heart J. 2018; 39:2526–39.

9. Mills EJ, Wu P, Chong G, Ghement I, Singh S, Akl EA, et al. Efficacy and safety of statin treatment for cardiovascular disease: a network meta-analysis of 170,255 patients from 76 randomized trials. QJM. 2011; 104:109–24.

10. Ruscica M, Macchi C, Morlotti B, Sirtori CR, Magni P. Statin therapy and related risk of new-onset type 2 diabetes mellitus. Eur J Intern Med. 2014; 25:401–6.

11. Shalev V, Chodick G, Silber H, Kokia E, Jan J, Heymann AD. Continuation of statin treatment and all-cause mortality: a population-based cohort study. Arch Intern Med. 2009; 169:260–8.

12. Rhee EJ, Kim HC, Kim JH, Lee EY, Kim BJ, Kim EM, et al. 2018 Guidelines for the management of dyslipidemia in Korea. J Lipid Atheroscler. 2019; 8:78–131.

13. Committee of Clinical Practice Guideline of the Korean Society of Lipid and Atherosclerosis (KSoLA). Korean guidelines for the management of dyslipidemia. 4th ed. Seoul: KSoLA;2018.

14. Korean Medical Guideline Information Center. Evidence-based guideline for dyslipidemia in primary care [Internet]. Seoul: Korean Academy of Medical Sciences;2020. [cited 2022 Jan 24]. Available from: https://www.guideline.or.kr/chronic/view.php?number=90.

15. Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020; 41:111–88.

16. Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019; 139:e1082–143.

17. Newman CB, Preiss D, Tobert JA, Jacobson TA, Page RL 2nd, Goldstein LB, et al. Statin safety and associated adverse events: a scientific statement from the American Heart Association. Arterioscler Thromb Vasc Biol. 2019; 39:e38–81.

18. Kajinami K, Tsukamoto K, Koba S, Inoue I, Yamakawa M, Suzuki S, et al. Statin intolerance clinical guide 2018. J Atheroscler Thromb. 2020; 27:375–96.

19. Kinoshita M, Yokote K, Arai H, Iida M, Ishigaki Y, Ishibashi S, et al. Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017. J Atheroscler Thromb. 2018; 25:846–984.

20. Calderon RM, Cubeddu LX, Goldberg RB, Schiff ER. Statins in the treatment of dyslipidemia in the presence of elevated liver aminotransferase levels: a therapeutic dilemma. Mayo Clin Proc. 2010; 85:349–56.

21. Hu M, Cheung BM, Tomlinson B. Safety of statins: an update. Ther Adv Drug Saf. 2012; 3:133–44.

22. Roth AD, Lee MY. Idiosyncratic Drug-induced liver injury (IDILI): potential mechanisms and predictive assays. Biomed Res Int. 2017; 2017:9176937.

23. Bjornsson E, Jacobsen EI, Kalaitzakis E. Hepatotoxicity associated with statins: reports of idiosyncratic liver injury post-marketing. J Hepatol. 2012; 56:374–80.

24. Stroes ES, Thompson PD, Corsini A, Vladutiu GD, Raal FJ, Ray KK, 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; 36:1012–22.

25. Selva-O’Callaghan A, Alvarado-Cardenas M, Pinal-Fernandez I, Trallero-Araguas E, Milisenda JC, Martinez MA, et al. Statin-induced myalgia and myositis: an update on pathogenesis and clinical recommendations. Expert Rev Clin Immunol. 2018; 14:215–24.

26. Thompson PD, Panza G, Zaleski A, Taylor B. Statin-associated side effects. J Am Coll Cardiol. 2016; 67:2395–410.

27. Neuvonen PJ, Niemi M, Backman JT. Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther. 2006; 80:565–81.

28. Bitzur R, Cohen H, Kamari Y, Harats D. Intolerance to statins: mechanisms and management. Diabetes Care. 2013; 36(Suppl 2):S325–30.

29. Luvai A, Mbagaya W, Hall AS, Barth JH. Rosuvastatin: a review of the pharmacology and clinical effectiveness in cardiovascular disease. Clin Med Insights Cardiol. 2012; 6:17–33.

30. Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJ, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010; 375:735–42.

31. Preiss D, Seshasai SR, Welsh P, Murphy SA, Ho JE, Waters DD, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA. 2011; 305:2556–64.

32. Rajpathak SN, Kumbhani DJ, Crandall J, Barzilai N, Alderman M, Ridker PM. Statin therapy and risk of developing type 2 diabetes: a meta-analysis. Diabetes Care. 2009; 32:1924–9.

33. Coleman CI, Reinhart K, Kluger J, White CM. The effect of statins on the development of new-onset type 2 diabetes: a meta-analysis of randomized controlled trials. Curr Med Res Opin. 2008; 24:1359–62.

34. Cho Y, Choe E, Lee YH, Seo JW, Choi Y, Yun Y, et al. Risk of diabetes in patients treated with HMG-CoA reductase inhibitors. Metabolism. 2015; 64:482–8.

35. Carter AA, Gomes T, Camacho X, Juurlink DN, Shah BR, Mamdani MM. Risk of incident diabetes among patients treated with statins: population based study. BMJ. 2013; 346:f2610.

36. Kim SH. Statin and the risk of new-onset diabetes mellitus. J Korean Med Assoc. 2017; 60:901–11.