The Use of Statins in Primary Prevention of Cardiovascular Disease: Benefits versus Risks

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Authors: Adji Prayitno Setiadi, Sylvi Irawati, Bobby Presley, Eko Setiawan, and Yosi Irawati Wibowo
Page Range: 129-138
Published in: World Heart Journal, 14#2 (2022)
ISSN: 1556-4002

ISBN: N/A Category:

Table of Contents

ABSTRACT

Background: Cardiovascular disease (CVD) remains a major global health issue. The use of statins in people with a history of CVD is generally well established, however, debate remains about their use for primary prevention in people without CVD. This narrative review aims to present studies related to the benefits and risks of taking statins for primary prevention of CVD. An internet search of the Cochrane Library (2006 to 2021) and PubMed (2006 to 2021) used the following keywords: Hydroxymethylglutaryl-CoA Reductase Inhibitors, statin OR statins; cardiovascular disease, heart disease, coronary disease; primary prevention. Systematic review/ meta-analyses-based articles were included in the review. The studies reported positive outcomes of statins, particularly in relation with reduction in all-cause mortality, non-fatal MI, and non-fatal stroke. Some adverse events were also reported, such as muscle problems, diabetes, liver dysfunctions, and renal and eye disorders, However, the risks attributable to statins were considerably lower and thus did not outweigh the benefits in preventing CVD. It should be acknowledged that the decision to initiate statins for primary prevention should not solely depend on the LDL-C value, but also on overall CVD risk factors for a particular individual, as can be seen in three major guidelines from the American College of Cardiology/ American Heart Association (ACC/AHA) – 2019, Canadian Society of Cardiology (CCS) – 2021, and the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) – 2019. The risks attributable to statins were relatively low, and thus did not outweigh the benefits in preventing CVD.

Keywords: statin, primary prevention, cardiovascular risk factor, cardiovascular disease

REFERENCES

[1] Mendis S. Global progress in prevention of cardiovascular disease. Cardiovasc Diagn Ther 2017; 7 (Suppl 1): S32-S38. doi: 10.21037/cdt.22017.21003.21006.
[2] Bloom D, Cafiero E, Jané-Llopis E, Abrahams-Gessel S, Bloom L, Fathima S, Feigl AB, Gaziano T, Mowafi M, Pandya A, Pretner K, Rosenberg L, Seligman B, Stein AZ, Weinstein C. The Global Economic Burden of Noncommunicable Diseases. Geneva: World Economic Forum; 2017. 46 pp.
[3] Arnett D, Blumenthal R, Albert M, Buroker A, Goldberger Z, Hahn EJ, Himmelfarb CD, Khera A, Lloyd-Jones D, McEvoy JW, Michos ED, Miedema MD, Muñoz D, Smith SC Jr, Virani SS, Williams KA Sr, Yeboah J, Ziaeian B. 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: e596-e646.
[4] ESC Scientific Document Group. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J 2021; 42: 3227-3337.
[5] Boekholdt S, Arsenault B, Mora S, Pedersen T, LaRosa J, Nestel P, Simes RJ, Durrington P, Hitman GA, Welch KM, DeMicco DA, Zwinderman AH, Clearfield MB, Downs JR, Tonkin AM, Colhoun HM, Gotto AM Jr, Ridker PM, Kastelein JP. Association of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B levels with risk of cardiovascular events among patients treated with statins: a meta-analysis. JAMA 2012; 307 (12): 1302-1309. doi: 10.1001/jama.2012.366.
[6] Mortensen M, Nordestgaard B. Elevated LDL cholesterol and increased risk of myocardial infarction and atherosclerotic cardiovascular disease in individuals aged 70–100 years: a contemporary primary prevention cohort. Lancet 2020; 396 (10293): 1644-1652. https://doi.org/1610.1016/S0140-6736(1620)32233-32239.
[7] Chou R, Dana T, Daeges M, Jeanne T. Statins for prevention of cardiovascular disease in adults: evidence report and systematic review for the US Preventive Services Task Force. JAMA 2016; 316 (19): 2008-2024. doi: 2010.1001/jama.2015.15629.
[8] Ray K, Seshasai S, Erqou S, Sever P, Jukema W, Ford I, Sattar N. Statins and all-cause mortality in high-risk primary prevention: a meta-analysis of 11 randomized controlled trials involving 65,229 participants. Arch Intern Med 2010; 170 (12): 1024-10231.
[9] Brugts J, Yetgin T, Hoeks S, Gotto A., Sheperd J, Westendorp R., de Craen AJ, Knopp RH, Nakamura H, Ridker P, van Domburg R, Deckers JW. The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials. BMJ 2009; 338: b.2376. doi: 2310.1136/bmj.b2376.
[10] Mills E, Rachlis B, Wu P, Devereaux P, Arora P, Perri D. Primary prevention of cardiovascular mortality and events with statin treatments: a network meta-analysis involving more than 65,000 patients. J Am Coll Cardiol 2008; 52 (22): 1769-1781.
[11] Tonelli M, Lloyd A, Clement F, Conly J, Husereau D, Hemmelgarn B, Klarenbach S, McAlister FA, Wiebe N, Manns B; Alberta Kidney Disease Network. Efficacy of statins for primary prevention in people at low cardiovascular risk: a meta-analysis. Can Med Assoc J 2011; 183 (16): e1189-1197. doi: 10.1503/cmaj.101280.
[12] Taylor F, Huffman M, Macedo A, Moore T, Burke M, Davey Smith G, Ward K, Ebrahim S. Statins for the primary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews 2013; Issue 1: Art. No.: CD004816. doi:10.1002/14651858.CD004816.pub5.8:b2376.
[13] Yebyo H, Aschmann H, Kaufmann M, Puhan M. Comparative effectiveness and safety of statins as a class and of specific statins for primary prevention of cardiovascular disease: A systematic review, meta-analysis, and network meta-analysis of randomized trials with 94,283 participants. Am Heart J 2019; 210: 18-28.
[14] Taylor M, Wells B, Smolak M. Statins and cancer: a meta-analysis of case-control studies. Eur J Cancer Prev 2008; 17: 259-268.
[15] Barbalata C, Tefas L, Achim M, Tomuta I, Porfire A. Statins in risk-reduction and treatment of cancer. World J Clin Oncol 2020; 11 (8): 573-588. doi: 510.5306/wjco.v5311.i5308.5573.
[16] Matsushita Y, Sugihara M, Kaburagi J, Ozawa M, Iwashita M, Yoshida S, Saito H, Hattori Y. Pravastatin use and cancer risk: a meta-analysis of individual patient data from long-term prospective controlled trials in Japan. Pharmacoepidemiol Drug Safety 2010; 19: 196-202.
[17] Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R, Barnes EH, Keech A, Simes J, Collins R. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010; 376, 1670-1681.
[18] Bonovas S, Filioussi K, Tsavaris N, Sitaras N. Statins and cancer risk: a literature-based meta-analysis and meta-regression analysis of 35 randomized controlled trials. J Clin Oncol 2006; 24: 4808-4817.
[19] Browning D, Martin R. Statins and risk of cancer: a systematic review and metaanalysis. Int J Cancer 2007: 120: 833-843.
[20] Cholesterol Treatment Trialists’ (CTT) Collaboration, Emberson JR, Kearney PM, Blackwell L, Newman C, Reith C, Bhala N, Holland L, Peto R, Keech A, Collins R, Simes J, Baigent C. Lack of effect of lowering LDL cholesterol on cancer: meta-analysis of individual data from 175,000 people in 27 randomised trials of statin therapy. PLoS One 2012; 7: e29849.
[21] Alberton M, Wu P, Druyts E, Briel M, Mills EJ. Adverse events associated with individual statin treatments for cardiovascular disease: an indirect comparison meta-analysis. QJM 2012; 105: 145-157.
[22] Rajpathak SN, Kumbhani DJ, Crandall J, Barzilai N, Alderman M, Ridker PM. Statin therapy and risk of developing type 2 diabetes: a meta-analysis. Diab Care 2009; 32: 1924-1929.
[23] Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJ, Seshasai SR, McMurray JJ, Freeman DJ, Jukema JW, Macfarlane PW, Packard CJ, Stott DJ, Westendorp RG, Shepherd J, Davis BR, Pressel SL, Marchioli R, Marfisi RM, Maggioni AP, Tavazzi L, Tognoni G, Kjekshus J, Pedersen TR, Cook TJ, Gotto AM, Clearfield MB, Downs JR, Nakamura H, Ohashi Y, Mizuno K, Ray KK, Ford I. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet 2010; 375: 735-742.
[24] Cooney MT, Dudina AL, Graham IM. Value and limitations of existing scores for the assessment of cardiovascular risk a review for clinicians. J Am Coll Cardiol 2009; 54 (14): 1209-1227.
[25] Cai T, Abel L, Langford O, Monaghan G, Aronson J, Stevens R, Lay-Flurrie S, Koshiaris C, McManus RJ, Richard Hobbs FD, Sheppard J. Associations between statins and adverse events in primary prevention of cardiovascular disease: systematic review with pairwise, network, and dose-response meta-analyses. BMJ 2021; 374: n1537. doi: 1510.1136/bmj.n1537.
[26] Josan K, Majumdar S, Mcalister FA. The efficacy and safety of intensive statin therapy: a meta-analysis of randomized trials. Can Med Assoc J 2008; 178, 576-584.
[27] Singh RB, Fedacko J, Elkilany GN, Palmiero P, Hristova K, Cornelissen G. Statins administration for primary prevention of stroke and coronary artery disease: A scientific statementof the International College of Cardiology. World Heart J 2019; 11(4): 255-260.
[28] Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, Chapman MJ, De Backer GG, Delgado V, Ference BA, Graham IM, Halliday A, Landmesser U, Mihaylova B, Pedersen TR, Riccardi G, Richter DJ, Sabatine MS, Taskinen MR, Tokgozoglu L, Wiklund O; ESC Scientific Document Group. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020; 41: 111-188.
[29] Pearson GJ, Thanassoulis G, Anderson TJ, Barry AR, Couture P, Dayan N, Francis GA, Genest J, Grégoire J, Grover SA, Gupta M, Hegele RA, Lau D, Leiter LA, Leung AA, Lonn E, Mancini GBJ, Manjoo P, McPherson R, Ngui D, Piché ME, Poirier P, Sievenpiper J, Stone J, Ward R, Wray W. 2021 Canadian Cardiovascular Society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in adults. Can J Cardiol 2021; 37: 1129-1150.
[30] Tsao CW, Aday AW, Almarzooq FI, Alonso A, Beaton AZ, Bittencourt MS, Boehme AK, Buxton AE, Carson AP, Commodore-Mensah Y, Elkind MSV, Evenson KR, Eze-Nliam C, Ferguson JF, Generoso G, Ho JE, Kalani R, Khan SS, Kissela BM, Knutson KL, Levine DA, Lewis TT, Liu J, Loop MS, Ma J, Mussolino ME, Navaneethan SD, Perak AM, Poudel R, Rezk-Hanna M, Roth GA, Schroeder EB, Shah SH, Thacker EL, VanWagner LB, Virani SS, Voecks JH, Wang NY, Yaffe K, Martin SS. Heart disease and stroke statistics — 2022 update: A report from the American Heart Association. Circulation 2022; 145 (8): e153-639. https://doi.org/10.1161/CIR.0000000000001052.