<p>Lovastatin, also known as the brand name product Mevacor, is a lipid-lowering drug and fungal metabolite derived synthetically from a fermentation product of <em>Aspergillus terreus</em>.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Boruta T, Bizukojc M: Production of lovastatin and itaconic acid by Aspergillus terreus: a comparative perspective. World J Microbiol Biotechnol. 2017 Feb;33(2):34. doi: 10.1007/s11274-017-2206-9. Epub 2017 Jan 19. (PubMed ID 28102516)" href="#reference-A174550">1</a></sup> Originally named Mevinolin, lovastatin belongs to the statin class of medications, which are used to lower the risk of cardiovascular disease and manage abnormal lipid levels by inhibiting the endogenous production of cholesterol in the liver.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Alberts AW, Chen J, Kuron G, Hunt V, Huff J, Hoffman C, Rothrock J, Lopez M, Joshua H, Harris E, Patchett A, Monaghan R, Currie S, Stapley E, Albers-Schonberg G, Hensens O, Hirshfield J, Hoogsteen K, Liesch J, Springer J: Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent. Proc Natl Acad Sci U S A. 1980 Jul;77(7):3957-61. (PubMed ID 6933445)" href="#reference-A174553">2</a></sup> More specifically, statin medications competitively inhibit the enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) Reductase,<sup class="text-reference-group"><a class="reference-popover-link" data-content="Moghadasian MH: Clinical pharmacology of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Life Sci. 1999;65(13):1329-37. doi: 10.1016/s0024-3205(99)00199-x. (PubMed ID 10503952)" href="#reference-A181421">12</a></sup> which catalyzes the conversion of HMG-CoA to mevalonic acid and is the third step in a sequence of metabolic reactions involved in the production of several compounds involved in lipid metabolism and transport including cholesterol, low-density lipoprotein (LDL) (sometimes referred to as "bad cholesterol"), and very low-density lipoprotein (VLDL). Prescribing of statin medications is considered standard practice following any cardiovascular events and for people with a moderate to high risk of development of CVD, such as those with Type 2 Diabetes. The clear evidence of the benefit of statin use coupled with very minimal side effects or long term effects has resulted in this class becoming one of the most widely prescribed medications in North America.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Anderson TJ, Gregoire J, Pearson GJ, Barry AR, Couture P, Dawes M, Francis GA, Genest J Jr, Grover S, Gupta M, Hegele RA, Lau DC, Leiter LA, Lonn E, Mancini GB, McPherson R, Ngui D, Poirier P, Sievenpiper JL, Stone JA, Thanassoulis G, Ward R: 2016 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult. Can J Cardiol. 2016 Nov;32(11):1263-1282. doi: 10.1016/j.cjca.2016.07.510. Epub 2016 Jul 25. (PubMed ID 27712954)" href="#reference-A181087">13</a>,<a class="reference-popover-link" data-content="Grundy SM, Stone NJ: 2018 American Heart Association/American College of Cardiology Multisociety Guideline on the Management of Blood Cholesterol: Primary Prevention. JAMA Cardiol. 2019 Apr 10. pii: 2730287. doi: 10.1001/jamacardio.2019.0777. (PubMed ID 30969322)" href="#reference-A181406">14</a></sup></p><p>Lovastatin and other drugs from the statin class of medications including <a href="https://go.drugbank.com/drugs/DB01076">atorvastatin</a>, <a href="https://go.drugbank.com/drugs/DB00175">pravastatin</a>, <a href="https://go.drugbank.com/drugs/DB01098">rosuvastatin</a>, <a href="https://go.drugbank.com/drugs/DB01095">fluvastatin</a>, and <a href="https://go.drugbank.com/drugs/DB00641">simvastatin</a> are considered first-line options for the treatment of dyslipidemia.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Anderson TJ, Gregoire J, Pearson GJ, Barry AR, Couture P, Dawes M, Francis GA, Genest J Jr, Grover S, Gupta M, Hegele RA, Lau DC, Leiter LA, Lonn E, Mancini GB, McPherson R, Ngui D, Poirier P, Sievenpiper JL, Stone JA, Thanassoulis G, Ward R: 2016 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult. Can J Cardiol. 2016 Nov;32(11):1263-1282. doi: 10.1016/j.cjca.2016.07.510. Epub 2016 Jul 25. (PubMed ID 27712954)" href="#reference-A181087">13</a>,<a class="reference-popover-link" data-content="Grundy SM, Stone NJ: 2018 American Heart Association/American College of Cardiology Multisociety Guideline on the Management of Blood Cholesterol: Primary Prevention. JAMA Cardiol. 2019 Apr 10. pii: 2730287. doi: 10.1001/jamacardio.2019.0777. (PubMed ID 30969322)" href="#reference-A181406">14</a></sup> Increasing use of the statin class of drugs is largely due to the fact that cardiovascular disease (CVD), which includes heart attack, atherosclerosis, angina, peripheral artery disease, and stroke, has become a leading cause of death in high-income countries and a major cause of morbidity around the world.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Kreatsoulas C, Anand SS: The impact of social determinants on cardiovascular disease. Can J Cardiol. 2010 Aug-Sep;26 Suppl C:8C-13C. doi: 10.1016/s0828-282x(10)71075-8. (PubMed ID 20847985)" href="#reference-A181084">15</a></sup> Elevated cholesterol levels, and in particular, elevated low-density lipoprotein (LDL) levels, are an important risk factor for the development of CVD.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Anderson TJ, Gregoire J, Pearson GJ, Barry AR, Couture P, Dawes M, Francis GA, Genest J Jr, Grover S, Gupta M, Hegele RA, Lau DC, Leiter LA, Lonn E, Mancini GB, McPherson R, Ngui D, Poirier P, Sievenpiper JL, Stone JA, Thanassoulis G, Ward R: 2016 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult. Can J Cardiol. 2016 Nov;32(11):1263-1282. doi: 10.1016/j.cjca.2016.07.510. Epub 2016 Jul 25. (PubMed ID 27712954)" href="#reference-A181087">13</a>,<a class="reference-popover-link" data-content="Kannel WB, Castelli WP, Gordon T, McNamara PM: Serum cholesterol, lipoproteins, and the risk of coronary heart disease. The Framingham study. Ann Intern Med. 1971 Jan;74(1):1-12. doi: 10.7326/0003-4819-74-1-1. (PubMed ID 5539274)" href="#reference-A181553">16</a></sup> Use of statins to target and reduce LDL levels has been shown in a number of landmark studies to significantly reduce the risk of development of CVD and all-cause mortality.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Authors unspecified: Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998 Nov 5;339(19):1349-57. doi: 10.1056/NEJM199811053391902. (PubMed ID 9841303)" href="#reference-A181090">17</a>,<a class="reference-popover-link" data-content="Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, Joyal SV, Hill KA, Pfeffer MA, Skene AM: Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004 Apr 8;350(15):1495-504. doi: 10.1056/NEJMoa040583. Epub 2004 Mar 8. (PubMed ID 15007110)" href="#reference-A181093">18</a>,<a class="reference-popover-link" data-content="Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ: Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008 Nov 20;359(21):2195-207. doi: 10.1056/NEJMoa0807646. Epub 2008 Nov 9. (PubMed ID 18997196)" href="#reference-A181096">19</a>,<a class="reference-popover-link" data-content="Nicholls SJ, Ballantyne CM, Barter PJ, Chapman MJ, Erbel RM, Libby P, Raichlen JS, Uno K, Borgman M, Wolski K, Nissen SE: Effect of two intensive statin regimens on progression of coronary disease. N Engl J Med. 2011 Dec 1;365(22):2078-87. doi: 10.1056/NEJMoa1110874. Epub 2011 Nov 15. (PubMed ID 22085316)" href="#reference-A181427">20</a>,<a class="reference-popover-link" data-content="Authors unspecified: MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002 Jul 6;360(9326):7-22. doi: 10.1016/S0140-6736(02)09327-3. (PubMed ID 12114036)" href="#reference-A181475">21</a>,<a class="reference-popover-link" data-content="Authors unspecified: Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S) Lancet. 1994 Nov 19;344(8934):1383-9. (PubMed ID 7968073)" href="#reference-A181538">22</a></sup> Statins are considered a cost-effective treatment option for CVD due to their evidence of reducing all-cause mortality including fatal and non-fatal CVD as well as the need for surgical revascularization or angioplasty following a heart attack.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Anderson TJ, Gregoire J, Pearson GJ, Barry AR, Couture P, Dawes M, Francis GA, Genest J Jr, Grover S, Gupta M, Hegele RA, Lau DC, Leiter LA, Lonn E, Mancini GB, McPherson R, Ngui D, Poirier P, Sievenpiper JL, Stone JA, Thanassoulis G, Ward R: 2016 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult. Can J Cardiol. 2016 Nov;32(11):1263-1282. doi: 10.1016/j.cjca.2016.07.510. Epub 2016 Jul 25. (PubMed ID 27712954)" href="#reference-A181087">13</a>,<a class="reference-popover-link" data-content="Grundy SM, Stone NJ: 2018 American Heart Association/American College of Cardiology Multisociety Guideline on the Management of Blood Cholesterol: Primary Prevention. JAMA Cardiol. 2019 Apr 10. pii: 2730287. doi: 10.1001/jamacardio.2019.0777. (PubMed ID 30969322)" href="#reference-A181406">14</a></sup> Evidence has shown that even for low-risk individuals (with &lt;10% risk of a major vascular event occurring within 5 years) statins cause a 20%-22% relative reduction in major cardiovascular events (heart attack, stroke, coronary revascularization, and coronary death) for every 1 mmol/L reduction in LDL without any significant side effects or risks.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Mihaylova B, Emberson J, Blackwell L, Keech A, Simes J, Barnes EH, Voysey M, Gray A, Collins R, Baigent C: The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet. 2012 Aug 11;380(9841):581-90. doi: 10.1016/S0140-6736(12)60367-5. Epub 2012 May 17. (PubMed ID 22607822)" href="#reference-A181397">24</a>,<a class="reference-popover-link" data-content="Taylor F, Huffman MD, Macedo AF, Moore TH, Burke M, Davey Smith G, Ward K, Ebrahim S: Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013 Jan 31;(1):CD004816. doi: 10.1002/14651858.CD004816.pub5. (PubMed ID 23440795)" href="#reference-A181403">23</a></sup></p><p>While all statin medications are considered equally effective from a clinical standpoint, <a href="https://go.drugbank.com/drugs/DB01098">rosuvastatin</a> is considered the most potent; doses of 10 to 40mg <a href="https://go.drugbank.com/drugs/DB01098">rosuvastatin</a> per day were found in clinical studies to result in a 45.8% to 54.6% decrease in LDL cholesterol levels, while lovastatin has been found to have an average decrease in LDL-C of 25-40%.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Henwood JM, Heel RC: Lovastatin. A preliminary review of its pharmacodynamic properties and therapeutic use in hyperlipidaemia. Drugs. 1988 Oct;36(4):429-54. doi: 10.2165/00003495-198836040-00003. (PubMed ID 3069436)" href="#reference-A174580">5</a>,<a class="reference-popover-link" data-content="Adams SP, Sekhon SS, Wright JM: Lipid-lowering efficacy of rosuvastatin. Cochrane Database Syst Rev. 2014 Nov 21;(11):CD010254. doi: 10.1002/14651858.CD010254.pub2. (PubMed ID 25415541)" href="#reference-A181409">25</a>,<a class="reference-popover-link" data-content="Pedersen TR, Faergeman O, Kastelein JJ, Olsson AG, Tikkanen MJ, Holme I, Larsen ML, Bendiksen FS, Lindahl C, Szarek M, Tsai J: High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA. 2005 Nov 16;294(19):2437-45. doi: 10.1001/jama.294.19.2437. (PubMed ID 16287954)" href="#reference-A181535">26</a>,<a class="reference-popover-link" data-content="Authors unspecified: Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S) Lancet. 1994 Nov 19;344(8934):1383-9. (PubMed ID 7968073)" href="#reference-A181538">22</a>,<a class="reference-popover-link" data-content="Jones PH, Davidson MH, Stein EA, Bays HE, McKenney JM, Miller E, Cain VA, Blasetto JW: Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial). Am J Cardiol. 2003 Jul 15;92(2):152-60. (PubMed ID 12860216)" href="#reference-A1793">27</a></sup> Potency is thought to correlate to tissue permeability as the more lipophilic statins such as lovastatin are thought to enter endothelial cells by passive diffusion, as opposed to hydrophilic statins such as <a href="https://go.drugbank.com/drugs/DB00175">pravastatin</a> and <a href="https://go.drugbank.com/drugs/DB01098">rosuvastatin</a> which are taken up into hepatocytes through OATP1B1 (organic anion transporter protein 1B1)-mediated transport.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Liao JK, Laufs U: Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol. 2005;45:89-118. doi: 10.1146/annurev.pharmtox.45.120403.095748. (PubMed ID 15822172)" href="#reference-A181424">31</a>,<a class="reference-popover-link" data-content="Elsby R, Hilgendorf C, Fenner K: Understanding the critical disposition pathways of statins to assess drug-drug interaction risk during drug development: it's not just about OATP1B1. Clin Pharmacol Ther. 2012 Nov;92(5):584-98. doi: 10.1038/clpt.2012.163. Epub 2012 Oct 10. (PubMed ID 23047648)" href="#reference-A181460">28</a></sup> Despite these differences in potency, several trials have demonstrated only minimal differences in terms of clinical outcomes between statins.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Authors unspecified: Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S) Lancet. 1994 Nov 19;344(8934):1383-9. (PubMed ID 7968073)" href="#reference-A181538">22</a>,<a class="reference-popover-link" data-content="Nicholls SJ, Ballantyne CM, Barter PJ, Chapman MJ, Erbel RM, Libby P, Raichlen JS, Uno K, Borgman M, Wolski K, Nissen SE: Effect of two intensive statin regimens on progression of coronary disease. N Engl J Med. 2011 Dec 1;365(22):2078-87. doi: 10.1056/NEJMoa1110874. Epub 2011 Nov 15. (PubMed ID 22085316)" href="#reference-A181427">20</a></sup></p>