고콜레스테롤혈증 치료에서 아토바스타틴 5mg과 10mg 사용 시의 효능 및 안전성 비교 연구

Comparison of Efficacy and Safety of Atorvastatin, 5mg and 10mg in the Treatment of Hypercholesterolemia

목적 : 지방공사 강남병원 순환기 내과에서 추적 검사 받는 고지혈중 환자 107명을 대상으로 아토바스타틴 저용량인 5mg과 10mg 사용시의 콜레스테롤 저하 효과, 부작용 등을 조사하였다. 방법 : NCEP guideline에 따라 약물 치료가 필요한 환자등 LDL-C 농도가 130mg/dL이상이면서 TG농도가 400mg/dL이하인 고콜레스테롤혈증 환자를 대상으로 5mg, 10mg 투여군으로 나누어 6개월 후의 지질 농도를 측정, 비교 분석하였다. 부작용 발생 여부에 대하여 매월 정기적 검진, 혈액 검사 등을 시행하였다. 2001년 3월부터 2003년 1월까지의 114 명중 107명이 최종적으로 연구대상에 포함되었다. 결과 : 남녀 비는 29:78이었고 전체 대상군중 16%에서 관상동맥 질환이, 고혈압이 84%에서, 당뇨병이 22%에서 있었다. 46명이 아토바스타틴 5mg, 61명이 10mg을 투여하였다. 각 그룹모두 6개월 후의 지질치는 HDL-C을 제외하고는 기저치에 비하여 감소하였다(p<0.05). 용량간의 지질치에 대한 비교는 차이가 없었다. 각 용량의 동등한 지질 감소 효과를 고려하면 NCEP guideline 목표 달성 정도는 비슷하다고 할 수 있겠다. 부작용은 모두 4명에게서 관찰되었는데 그 중 1예는 근육통이 심해 약물 투여를 중단하였다. 나머지 3예는 부작용이 경미해 약물 투여를 계속하였다. 5mg용량이 안전성에 대하여 우수하였다(p=0.04). 결론 : 아토바스타틴 5mg, 10mg 모두 LDL-C을 저하시켜 관상동맥 질환을 예방하는데 효과적이었다. 관상동맥 질환에 대한 NCEP 10-year risk가 10% 미만인 군에서는, 부작용과 지질 저하에 관한 동등한 효과를 고려할 때 5mg이 초기 용량으로 추천될 수 있겠고 10%이상인 군에서는 20mg이상을 아토바스타틴의 초기 용량으로 추천할 수 있겠다.

Background : Coronary heart disease(CHD) is a major cause of morbidity and mortality in modern era. Hypercholesterolemia is a major risk factor for CHD. Atorvastatin is the most potent drug currently available for lowering low density lipoprotein(LDL) cholesterol. This study compared the efficacy and safety of 6 month therapy with atorvastatin 5mg and 10mg per day. Methods : A total of 114 men and women with serum LDL ${cholesterol{\geq}130mg/dL\;and\;triglycerides{\leq}400mg/dL}$ who need therapy according to National Cholesterol Education Program(NCEP) Adult Treatment Panel(ATP) III guideline were followed up for 6 months on outpatient basis. Atorvastatin 5mg was administered to 46 patients and 10mg to 61 patients per day. Lipid parameters were checked for 6 months and compared with baseline(within-treatment) and according to dose(between-treatment). Serum LDL cholesterol, triglycerides, high density lipoprotein(HDL) cholesterol change were checked according to their baseline, age, sex. NCEP ATP III target serum LDL cholesterol concentration achieving rate was compared between two treatment groups. Results : A total of 107 patients completed the 6-month schedule. Of the 107 patients, 29 patients were men and 78 patients were women. Both treatment groups had statistically significant within-treatment mean percent decreases from baseline to 6 month in total cholesterol, triglycerides, LDL cholesterol, LDL cholesterol/HDL cholesterol, and total cholesterol/HDL cholesterol ratio. In between-treatment comparison, both comparator groups had no statistically significant change in all of lipid parameters. LDL cholesterol, triglycerides had statistically significant LDL cholesterol percent decrement according to their baseline level. ${{\ll}(LDL\;cholesterol,{\geq}160mg/dL,{\leq}160mg/dL)\;(triglycerides,\;{\geq}250mg/dL,\;150{\leq}250mg/dL,\;<150mg/dL){\gg}\;Old\;age({\geq}65)}$ had statistically significant percent decrement in LDL cholesterol after 6 months in 10mg-administered group, but not in 5mg administered group. Gender had no effect in LDL cholesterol decrement. Absolute change were also included in statistical analysis. Above all-mentioned notions including between-treatment changes, LDL-C, HDL-G, TG chnges according to baseline level, LDL-C changes according to age and sex were same at absolute change comparison. In both comparator groups, NCEP target LDL cholesterol concentration achieving rate was same, considering the same efficacy for LDL cholesterol lowering and baseline LDL cholesterol difference. Atorvastatin 5mg and 10mg were well tolerated for 6 months. Only 3 patients(5%) in 10mg group had mild drug-related adverse effect. 5mg atorvastatin had statistically significant superior safety. Conclusion: In patients with hypercholesterolemia in Korea, both low doses were effective for lowering total cholesterol, LDL cholesterol, triglycerides and well tolerated.(within-treatment) No difference in efficacy was observed between treatment groups. If we hypothesize that both low doses have same efficacy and 5mg atorvastatin have superior safety, and if we consider NCEP 10-year risk for CHD, we can conclude that 5mg atorvastatin can be administered to patients who belong to NCEP 10-year risk<10%, but for patients who belong to NCEP 10-year $risk{\geq}10%$, more than 10mg of atorvastatin should be prescribed.