Re-Evaluation of Efficacy of Moderate-Intensity Statins in Korean Patients with Type 2 Diabetes Mellitus

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Diabetes Metab J. 2017;41(1):20-22
Publication date (electronic) : 2017 February 16
doi :
Department of Internal Medicine and Institute of Health Sciences, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea.
Corresponding author: Soo Kyoung Kim. Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, 79 Gangnam-ro, Jinju 52727, Korea.

Statins are competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, a rate-limiting enzyme in the cholesterol biosynthesis pathway [1]. Inhibiting cholesterol synthesis reduces secretion of apo-lipoprotein B-containing lipoproteins from the liver and upregulates low density lipoprotein (LDL) receptor activity, resulting in lower plasma LDL cholesterol (LDL-C).

Many clinical trials have consistently demonstrated that lowering LDL-C levels with statins is associated with reduced cardiovascular disease (CVD) event rates [2345]. Type 2 diabetes mellitus (T2DM) is a risk factor for macrovascular diseases, and controlling dyslipidemia is important for the prevention of CVD. The third report from the National Cholesterol Education Program-Adult Treatment Panel recommends reducing LDL-C levels to <100 mg/dL for primary prevention, and <70 mg/dL for secondary prevention [6]. However, the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines does not recommend a specific target level of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults, but rather recommends the use of a specific statin dose based on its lipid-lowering efficacy from the results of previous clinical trials [7]. However, the treatment guide-lines for dyslipidemia from the Korean Diabetes Association suggest an LDL-C target level [8], which has made treatment guidelines for dyslipidemia controversial. One of these debates concerns the appropriate statin and dose to lower lipid levels. Significant ethnic differences and heterogeneity exist in the response to statin, and statin efficacy in Asian populations differs from that in Caucasians. A lower statin dose than that used in Caucasian populations can be used to achieve a similar therapeutic effect in Asian populations. Japanese patients who received 5 mg of simvastatin daily for 6 months decreased their LDL-C level by 26%, which was similar to the effect of 20 mg of simvastatin daily in Western studies [9]. Another Asian study showed that patients who received 10 mg of atorvastatin or simvastatin reduced their LDL-C levels by 42.5% and 34.8%, respectively [10]. However, higher doses are required for similar LDL-C reductions in Caucasians. Few studies have compared the efficacy among statins in Korean patients [11]. Committee of clinical practice guideline [8] reported that a moderate-intensity statins was sufficient to achieve the target LDL-C level recommended by the Korean Diabetes Association. Kong et al. [12] supported the difference in statin efficacy in Korean when compared to Caucasian. Kong et al. [12] evaluated the efficacy of the moderate-intensity statins among Korean patients with T2DM. The study results showed that about 92.1% of patients with T2DM taking a moderate-intensity statin achieved the target LDL-C level (<100 mg/dL). Furthermore, after treatment with moderate-intensity statins for 6 months, 38.3% of the patients had reductions in their LDL-C levels by between 30% and 50%, and 42.3% of the patients had a reductions in their LDL-C levels by greater than 50% from their baseline levels [12]. These LDL reductions were higher than those observed in Caucasians [13]. As mentioned by the authors, the discrepancy in the efficacy of statins between Asians and Caucasians has been reported previously. A genetic difference in statin metabolism could explain this ethnic difference in LDL-lowering efficacy of statins [14]. Polymorphisms in the cytochrome P450 family of enzymes or drug target receptors are associated with differences in drug pharmacokinetics and pharmacodynamics [14]. Actually, some Asians metabolize statins slower, leading to higher plasma statin concentration [1516]. These differences in drug pharmacokinetics and pharmacodynamics could result in inter-subject variability within the same ethnic group. Kong et al. [12] also showed that 19.4% of participants achieved <30% reduction in their LDL-C levels after taking a moderate-intensity statins, whereas others achieved a greater reduction in their LDL-C levels. Although differences in age, comorbid conditions, physical activity, or socioeconomic status may lead to a different statin efficacy, the difference in drug response could cause this difference in statin efficacy [1516].

The different responses to statins raise concerns about an in-creased risk for adverse events, because most adverse effects from statins are dose-related [1415]. However, no increase in the frequency of adverse events has been reported in Asian patients taking lower or higher doses of a statin [1718]. Kong et al. [12] also reported few adverse events including musculoskeletal and hepatic adverse events during the use of a moderate-intensity statins.

The 2013 ACC/AHA guidelines use the 10-year atherosclerotic CVD risk for choosing the initial statin and dose [7]. Dyslipidemia-related mortality and the reduction in CVD frequency after dyslipidemia differ between Asians and Caucasians [1920]. The ACC/AHA guidelines recommended the use of a moderate- to high-intensity statins in patients with T2DM. However, studies based on the ACC/AHA guidelines included a limited number of Asian subjects. Many studies have reported differences in statin efficacy, and Kong et al. [12] also showed that the LDL-lowering effects of statin in Korean differ from those in Caucasians, indicating that a lower intensity statin could be sufficient to reduce CVD risk in Korean subjects. Further studies are needed to develop guidelines that reflect the actual CVD risk in Korean subjects with dyslipidemia and the appropriate statin for reducing their CVD risk.


CONFLICTS OF INTEREST: No potential conflict of interest relevant to this article was reported.


1. Endo A. The discovery and development of HMG-CoA reductase inhibitors. J Lipid Res 1992;33:1569–1582. 1464741.
2. 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. JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008;359:2195–2207. 18997196.
3. Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM, Ford I, Gaw A, Hyland M, Jukema JW, Kamper AM, Macfarlane PW, Meinders AE, Norrie J, Packard CJ, Perry IJ, Stott DJ, Sweeney BJ, Twomey C, Westendorp RG. PROSPER study group PROspective Study of Pravastatin in the Elderly at Risk. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002;360:1623–1630. 12457784.
4. The Scandinavian Simvastatin Survival Study (4S). Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease. Lancet 1994;344:1383–1389. 7968073.
5. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. 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;339:1349–1357. 9841303.
6. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). National Cholesterol Education Program Expert Panel on Detection E, Treatment of High Blood Cholesterol in A. Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002;106–3143. –3421.
7. Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PW, Eddleman KM, Jarrett NM, LaBresh K, Nevo L, Wnek J, Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH, DeMets D, Hochman JS, Kovacs RJ, Ohman EM, Pressler SJ, Sellke FW, Shen WK, Smith SC Jr, Tomaselli GF. American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;129(25 Suppl 2):S1–S45. 24222016.
8. Committee of clinical practice guideline. Treatment guideline for diabetes 5th edth ed. Seoul: Korean Diabetes Association; 2015.
9. Matsuzawa Y, Kita T, Mabuchi H, Matsuzaki M, Nakaya N, Oikawa S, Saito Y, Sasaki J, Shimamoto K, Itakura H. J-LIT Study Group. Sustained reduction of serum cholesterol in low-dose 6-year simvastatin treatment with minimum side effects in 51,321 Japanese hypercholesterolemic patients. Circ J 2003;67:287–294. 12655157.
10. Wu CC, Sy R, Tanphaichitr V, Hin AT, Suyono S, Lee YT. Comparing the efficacy and safety of atorvastatin and simvastatin in Asians with elevated low-density lipoprotein-cholesterol: a multinational, multicenter, double-blind study. J Formos Med Assoc 2002;101:478–487. 12353340.
11. Kwon JE, Kim Y, Hyun S, Won H, Shin SY, Lee KJ, Kim SW, Kim TH, Kim CJ. Cholesterol lowering effects of low-dose statins in Korean patients. J Lipid Atheroscler 2014;3:21–28.
12. Kong SH, Koo BK, Moon MK. Efficacy of moderate intensity statins in the treatment of dyslipidemia in Korean patients with type 2 diabetes mellitus. Diabetes Metab J 2017;41:23–30. 28029012.
13. Edwards JE, Moore RA. Statins in hypercholesterolaemia: a dose-specific meta-analysis of lipid changes in randomised, double blind trials. BMC Fam Pract 2003;4:18. 14969594.
14. Lee E, Ryan S, Birmingham B, Zalikowski J, March R, Ambrose H, Moore R, Lee C, Chen Y, Schneck D. Rosuvastatin pharmacokinetics and pharmacogenetics in white and Asian subjects residing in the same environment. Clin Pharmacol Ther 2005;78:330–341. 16198652.
15. Birmingham BK, Bujac SR, Elsby R, Azumaya CT, Zalikowski J, Chen Y, Kim K, Ambrose HJ. Rosuvastatin pharmacokinetics and pharmacogenetics in Caucasian and Asian subjects residing in the United States. Eur J Clin Pharmacol 2015;71:329–340. 25630984.
16. Kim K, Johnson JA, Derendorf H. Differences in drug pharmacokinetics between East Asians and Caucasians and the role of genetic polymorphisms. J Clin Pharmacol 2004;44:1083–1105. 15342610.
17. Saito Y, Goto Y, Dane A, Strutt K, Raza A. Randomized dose-response study of rosuvastatin in Japanese patients with hypercholesterolemia. J Atheroscler Thromb 2003;10:329–336. 15037821.
18. Japan Cholesterol Lowering Atorvastatin Study (J-CLAS) Group. Efficacy of atorvastatin in primary hypercholesterolemia. Am J Cardiol 1997;79:1248–1252. 9164896.
19. Nakamura H, Arakawa K, Itakura H, Kitabatake A, Goto Y, Toyota T, Nakaya N, Nishimoto S, Muranaka M, Yamamoto A, Mizuno K, Ohashi Y. MEGA Study Group. Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial. Lancet 2006;368:1155–1163. 17011942.
20. Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, McKillop JH, Packard CJ. West of Scotland Coronary Prevention Study Group. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995;333:1301–1307. 7566020.

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