斯達汀類藥物治療第二型糖尿病的高血脂及其安全性探討

Statins for Diabetic Hyperlipidemia and Their Safety

10.3966/168232812019032901001

蔡崇煌(Chung-Huang Tsai)；李篤宜(Du-Yi Lee)；黃素雲(Su-Yun Huang)；張加憲(Chia-Hsien Chang)；張惠雯(Hui-Wen Chang)

高血脂症 ； 降脂療法 ； 低密度脂蛋白膽固醇 ； 心肌梗塞 ； 新生糖尿病 ； hyperlipidemia ； lipid-lowering therapy ； low-density lipoprotein cholesterol ； myocardial infarction ； new-onset diabetes

台灣家庭醫學雜誌

29卷1期（2019 / 03 / 01）

1 - 11

繁體中文

在三高之高血糖、高血壓及高血脂的治療中，高血脂症較易被病患及醫師忽視，但就心肌梗塞的風險而言，長期的高血脂症遠高於糖尿病及高血壓，特別是血漿中低密度脂蛋白膽固醇，更需追踪及治療。目前其治療目標為低一點比較好及越早治療越好，然斯達汀類藥物治療所造成過低的LDL-C，可能導致醫師及病患擔心其安全性或副作用，例如新生糖尿病或認知功能影響。本文舉一三高個案，以statins治療高血脂的過程，並回顧部份具有里程碑意義的降脂療法藥物試驗及其安全性或副作用，以提供國內醫療人員的參考。

Compared to hyperglycemia and hypertension, hyperlipidemia appears to receive less attention from both patients and physicians, yet long-term hyperlipidemia incurs much higher risk of myocardial infarction than hyperglycemia and hypertension. Among different lipid parameters, plasma low-density lipoprotein cholesterol (LDL-C) is in greater need to be tracked and treated. Treatment for LDL-C emphasizes ＂the lower, the better＂ and ＂the sooner, the better.＂ However, capable of producing a much lower LDL-C, statin treatment may cause physicians and patients to worry about its safety and side effects, such as new-onset diabetes or incident diabetes and cognitive dysfunction. The article showed how the process of applying statin therapy to treat hyperlipidemia in a diabetes case. Moreover, several landmark statins outcome trials of lipid-lowering therapy (LLT) were also reviewed with a focus on examining their applications, safety, and side effects to provide a reference for medical professionals.

1. Antons, KA,Williams, CD,Baker, SK,Phillips, PS(2006).Clinical perspectives of statin-induced rhabdomyolysis.Am J Med,119,400-409.
2. Assmann, G,Schulte, H(1988).The Prospective Cardiovascular Munster (PROCAM) study: prevalence of hyperlipidemia in persons with hypertension and/or diabetes mellitus and the relationship to coronary heart disease.Am Heart J,116,1713-1724.
3. Baigent, C,Blackwell, L,Emberson, J(2010).Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials.Lancet,376,1670-1681.
4. Boey, E,Gay, GM,Poh, KK,Yeo, TC,Tan, HC,Lee, CH(2016).Visit-to-visit variability in LDL-and HDL-cholesterol is associated with adverse events after ST-segment elevation myocardial infarction: A 5-year follow-up study.Atherosclerosis,244,86-92.
5. Brown, MS,Goldstein, JL(1986).A receptor-mediated pathway for cholesterol homeostasis.Science,232,34-47.
6. Bruckert, E,Hayem, G,Dejager, S,Yau, C,Begaud, B(2005).Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients--the PRIMO study.Cardiovasc Drugs Ther,19,403-414.
7. Cannon, CP,Braunwald, E,McCabe, CH(2004).Intensive versus moderate lipid lowering with statins after acute coronary syndromes.N Engl J Med,350,1495-1504.
8. Chrispin, J,Martin, SS,Hasan, RK(2013).Landmark lipid-lowering trials in the primary prevention of cardiovascular disease.Clin Cardiol,36,516-523.
9. Colhoun, HM,Betteridge, DJ,Durrington, PN(2004).Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial.Lancet,364,685-696.
10. Everett, BM,Mora, S,Glynn, RJ,MacFadyen, J,Ridker, PM(2014).Safety profile of subjects treated to very low low-density lipoprotein cholesterol levels (<30 mg/dl) with rosuvastatin 20 mg daily (from JUPITER).Am J Cardiol,114,1682-1689.
11. Gitt, AK,Lautsch, D,Ferrieres, J(2017).Cholesterol target value attainment and lipid-lowering therapy in patients with stable or acute coronary heart disease: Results from the Dyslipidemia International Study II.Atherosclerosis,266,158-166.
12. Giugliano, RP,Wiviott, SD,Blazing, MA(2017).Long-term safety and efficacy of achieving very low levels of low-density lipoprotein cholesterol: a prespecified analysis of the IMPROVE-IT Trial.JAMA Cardiol,2,547-555.
13. Grundy, SM,Cleeman, JI,Merz, CN,National Heart, Lung, and Blood Institute,American College of Cardiology Foundation,American Heart Association(2004).Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines.Circulation,110,227-239.
14. Jones, PH,Davidson, MH,Stein, EA(2003).Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial).Am J Cardiol,92,152-160.
15. LaRosa, JC,Grundy, SM,Waters, DD(2005).Intensive lipid lowering with atorvastatin in patients with stable coronary disease.N Engl J Med,352,1425-1435.
16. Nordestgaard, BG,Chapman, MJ,Humphries, SE(2013).Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society.Eur Heart J,34,3478-3490.
17. Parker, BA,Capizzi, JA,Grimaldi, AS(2013).Effect of statins on skeletal muscle function.Circulation,127,96-103.
18. Preiss, D,Seshasai, SR,Welsh, P(2011).Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis.JAMA,305,2556-2564.
19. Ridker, PM(2009).The JUPITER trial: results, controversies, and implications for prevention.Circ Cardiovasc Qual Outcomes,2,279-285.
20. Sabatine, MS,Giugliano, RP,Keech, AC(2017).FOURIER Steering Committee and Investigators: Evolocumab and clinical outcomes in patients with cardiovascular disease.N Engl J Med,376,1713-1722.
21. Stone, NJ,Robinson, JG,Lichtenstein, AH(2014).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.J Am Coll Cardiol,63,2889-2934.
22. Takaguri, A,Satoh, K,Itagaki, M,Tokumitsu, Y,Ichihara, K(2008).Effects of atorvastatin and pravastatin on signal transduction related to glucose uptake in 3T3L1 adipocytes.J Pharmacol Sci,107,80-89.
23. Toth, PP,Dayspring, TD(2011).Drug safety evaluation of rosuvastatin.Expert Opin Drug Saf,10,969-986.
24. Turner, RC,Millns, H,Neil, HA(1998).Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS: 23).BMJ,316,823-828.
25. Wiviott, SD,Cannon, CP,Morrow, DA,Ray, KK,Pfeffer, MA,Braunwald, E(2005).Can low-density lipoprotein be too low? The safety and efficacy of achieving very low low-density lipoprotein with intensive statin therapy: a PROVE IT-TIMI 22 substudy.J Am Coll Cardiol,46,1411-1416.
26. Zieve, FJ,Kalin, MF,Schwartz, SL,Jones, MR,Bailey, WL(2007).Results of the glucose-lowering effect of WelChol study (GLOWS): a randomized, double-blind, placebo-controlled pilot study evaluating the effect of colesevelam hydrochloride on glycemic control in subjects with type 2 diabetes.Clin Ther,29,74-83.
27. 邱春吉,陳世明,李炳鈺,戴慶玲,江吉文(2012)。高危險群門診病患 Statin 類藥物治療型態與費用效益評估。台灣醫學，16，1-12。
28. 黃光聖(2012)。Statin 類藥物引發坐骨神經痛：病例報告。南臺灣醫學雜誌，8，92-95。