PHARMACOTHERAPEUTICS pissn 1975-8456 / eissn 2093-5951 http://dx.doi.org/10.5124/jkma.2014.57.10.857 이상적인혈중콜레스테롤조절지침 : 2013 년 ACC/AHA 권고안분석 최효인 한기훈 울산대학교의과대학서울아산병원심장내과 The ideal management of blood cholesterol: a review of the updated 2013 ACC/AHA cholesterol guideline for reducing cardiovascular risk Hyo-In Choi, MD Ki Hoon Han, MD Division of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Atherosclerotic cardiovascular disease (ASCVD) is the most important public health problem worldwide in terms of the size of expenditures in most healthcare budgets. In November 2013, the American College of Cardiology and American Heart Association (ACC/AHA) released a clinical practice guideline on the treatment of blood cholesterol to reduce ASCVD risk in adults. Based on the design and results of the randomized clinical trials and meta-analyses published through July 2013, four groups of individuals were identified for whom an extensive body of randomized clinical tria evidence demonstrated a clear reduction in ASCVD events from statin therapy with a good margin of safety. Together with ASCVD, in severe hypercholesterolemic (low-density lipoprotein cholesterol 190 mg/dl) or diabetic subjects, the guideline recommends the use of statins if the newly-developed Pooled Cohort Equations estimate a 10-year ASCVD risk of equal to or higher than 7.5%. The guideline recommendations represent a new paradigm for treating cholesterol focused on using the appropriate intensity of statin therapy for those most likely to benefit, while the guideline has eliminated low-density lipoprotein cholesterol and non high density lipoprotein cholesterol targets. Non-statin therapies were discouraged due to the lack of evidence for their production of acceptable ASCVD risk reduction benefits. This radical shift away from the set of previous guidelines has created controversy and confusion. This article reviews the 2013 ACC/AHA guideline for the treatment of blood cholesterol to reduce ASCVD risk in adults and the optimal strategies for using this guideline in clinical practice. Key Words: Guideline; Cholesterol; Cardiovascular risk; Statin Received: June 3, 2014 Accepted: June 17, 2014 Corresponding author: Ki Hoon Han E-mail: steadyhan@amc.seoul.kr Korean Medical Association This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons. org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 서론 죽상경화성심혈관질환은사망및삶의질저하뿐만아니라막대한의료비용을발생시키는가장흔한원인중하나이다. 2013년미국통계에따르면미국인 3명중 1명이심혈관질환에의하여사망한다 [1]. 죽상경화성심혈관질환은건강한 이상적인혈중콜레스테롤조절지침 : 2013 년 ACC/AHA 권고안분석 857
Table 1. Type and dose of statins according to the LDL-C lowering intensity High-intensity Intermediate-intensity Low-intensity Mean LDL-C reduction >50% Atorvastatin 40 a) -80 mg Rosuvastatin 20 mg Mean LDL-C reduction 30%-50% Atorvastatin 10 mg Rosuvastatin 10 mg Simvastatin 20-40 mg Pravastatin 40 mg Lovastatin 40 mg Fluvastatin 80 mg Pitavastatin 2-4 mg Mean LDL -C reduction <30% Pravastatin 10-20 mg Lovastatin 20mg All statins and specified doses were proven by randomized clinical trials except pitavastatin, which was approved by Food and Drug Administration, but not proved by randomized controlled trial. LDL-C, low-density lipoprotein cholesterol. a) Was proved by IDEAL study. 생활습관및고혈압조절, 혈중지질농도조절을통한예방효 과가있는것이증명되어있어이에대한적극적인조절이중 요하다할수있겠다. 2013 년 11 월미국심장학회 (American College of Cardiology and American Heart Association, ACC/AHA) 는성인의심혈관질환위험도감소를위한새로운 혈중콜레스테롤조절지침을발표한바있다 [2]. 2001 년소위 National Cholesterol Education Program/Adult Treatment Panel III (NCEP-III/ATP-III) 지침 [3] 이나온이후십수년 만의대규모개정으로서신뢰할수있는지침마련을위하여 의학협회에서제시된진료지침원칙 [4] 을준수하고자하였다. 금번조절지침의가장단단한뼈대는기왕에이루어진대규 모임상결과만을토대로하여확실한증거만을중심으로한 지침을제시하였다는것이다. 즉실험연구, 동물실험, 역학분 석및기타관찰연구의결과들은반영하지않고무작위대조시 험과메타분석의결과에서얻어진결과만을토대로내용을작 성하여개개의지침은강한정도의권고 / 증거수준 (class of recommendation/level of evidence) 을가지고있다. 그러나한편으로 2013 ACC/AHA 진료지침은기존에발 표되어널리사용되던 2001 NCEP-III/ATP-III [3], 2011 ESC/EAS (European Society of Cardiology and European Atherosclerosis Society) 조절지침 [5] 등이전에발표 되었던지침들과는그접근법, 치료방법, 위험군의산정등 에있어심대한변화를보이고있어학계와임상의사들에게 큰논란을불러일으켰다. 즉의료진입장에서혈중콜레스 테롤을현실적으로편리하게적용하고자조절의판단흐름 을최대한단순화하고자하였다. 즉, 스타틴의효용이확실한그룹을크게 4군으로나누어단계적으로접근하도록하고있으며해당군들에대하여어떠한스타틴을얼마나복용하는것이이상적인지를서술하고있다. 본지침은스타틴의종류와용량을세분화하여저밀도지단백콜레스테롤 (low-density lipoprotein cholesterol, LDL-C) 의강하효과정도에따라기저치대비 50% 이상의강하효과를보이는경우를고강도, 30-50% 의강하효과를보이는경우를중강도, 그이하를저강도로정의하였고그들중임상연구를통한근거가확실한용량을표시하여구분하였다. 한편으로는모든임상연구를통틀어 75세이상의고령자에는스타틴의효과검증이미흡하다는점을인정하여같은조건의저연령층보다한단계약한스타틴용량을권고하며, 또한스타틴을지속적으로장기투여하였을때의안정성이우려되는경우는한단계약한스타틴용량을권고하고있다. 본논문에서는 4그룹의대상군들의특성에대하여간략한정리설명을하고각부분에대한해석또는객관적주관적논의를함으로써특히한국인들에게이러한지침들을어떻게적용할수있는지를정리하고자노력하였다. 이번의콜레스테롤조절지침과함께별도의논문을통하여심혈관질환자의위험도관리를위해건강한식이와생활습관교정이모든치료와병행되어야한다고기술하고있다 [6]. 본논문은주로약물치료에주안점을두어작성하였으므로비약물요법에대한자세한논의는유보하기로한다. 권고되는스타틴의용량및용법 Table 1은이번진료지침에서권고되는스타틴의용량및용법을나타내고있다. 서론에서간략히언급한바와같이새로운진료지침에서는 LDL-C, non-high-density lipoprotein cholesterol (HDL-C) 및 HDL-C에의존한특정목표치를삭제하는대신기저치대비콜레스테롤강하효과에따른스타틴의종류와용량으로구분하여명시하고있다. 표의굵은활자체로표시된스타틴의용량이무작위대조실 858 대한의사협회지
Choi HI Han KH Cholesterol management guideline update Atherosclerotic vascular disease - Coronary artery disease or 50% stenosis - Stroke or transient ischemic attack or 50% stenosis in carotid or ICA - Peripheral artery disease or 50% stenosis Acute and unstable condition? Yes High-intensity statins Intermediate-intensity statins with evidence Maintain LDL-C <100 and 40 mg/dl Figure 1. Statin therapy in patients with clinical atherosclerotic cardiovascular disease. If low-density lipoprotein cholesterol (LDL-C) <40 mg/dl, lower statin dose or switch to lower intensity statins with evidence. If LDL-C >100 mg/dl, check compliance and increase statin dose or switch to higher intensity statins with evidence or consider adding nonstatins. ICA, intracranial artery. 험에서심혈관질환의위험도를감소시킴이증명된약제와 각각의용량들이며미국식품의약국승인은받았지만무작 위대조실험을통한효과가증명되지않은약제와용량은이 탤릭체로표시되어있다. 무작위대조실험에의하여도출된 증거에따라, 고강도스타틴치료는기저치대비 50% 이상 의 LDL-C 강하효과가있는약제, 중강도스타틴치료는기 저치대비 30% 에서 50% 의 LDL-C 강하효과가있는약제, 저강도스타틴치료는기저치대비 30% 미만의 LDL-C 강 하효과가있는약제들로구성되어있다. 스타틴의효용이확실한네그룹의대상자군들 1. 제 1 군 : 죽상경화성심혈관질환자 죽상경화성심혈관질환자는관상동맥심질환자 ( 급성관 상동맥증후군, 심근경색, 안정형협심증, 관상동맥또는기 타동맥재개통술의병력 ), 뇌졸중 ( 일과성허혈발작 ), ( 죽상 경화증에의한 ) 말초동맥질환의세가지로정의되었다. 뇌 졸중은뇌경색에제한하는것이좋다고판단되는데, 출혈 성뇌졸중은고용량의스타틴을복용하였을때에위험도증 가를보이는결과가다수존재하고 [7] 소혈관질환에의한 소위열공뇌졸중 (lacunar infarct) 에대한스타틴의효과 는확실히증명된바없기때문이다. 스타틴의뇌졸중예 Yes No No Age <75 years or - Safety concerns for statins - Statin intolerance 방효과정도는심혈관질환의병력유무와상관관계없지만관상동맥질환의예방효과보다정도가약하기때문에 [8] 뇌경색병력환자에서 2차예방의목적으로스타틴을투약할경우, 뇌졸중의종류를세분화하여스타틴복용군여부를판단하는것이좋겠다. 한편말초동맥죽상경화질환예방에대한스타틴의효과를검증한결과는근거가부족하며사실상스타틴치료와함께흡연, 당뇨등기타위험인자들의교정이중요시되고있다 [9]. 한국의경우증상없이관동맥및경동맥등의협착이발견되는경우가많으므로 50% 이상의협착이관동맥, 경동맥, 말초동맥에증상없이발견될때는본지침에서의언급은없으나 NCEP-III 기준에근거하여관상동맥질환과말초혈관질환상태에준하여조절을하여도무방하리라판단된다. 소위 2차예방으로분류되는제1군에게권고되는스타틴은고강도의스타틴이며 75세이상의고령이나스타틴의치료에부작용등으로유지가어려울경우한단계완화한중강도의스타틴을사용하도록권고하고있다. 대규모무작위배정임상시험의결과에의해 atorvastatin 80 mg [10-12] 과 JUPITER 연구에서의 rosuvastatin 20 mg의 LDL-C 감소효과가기저치에비해평균 50% 이상인것으로판단되므로스타틴에대한금기가없는한권장된다. 한편메타분석에서는스타틴은오래복용할수록심혈관질환의예방효과가극대화된다는보고는존재하지만얼마나오래고용량을유지하여야하는지에대하여서는증거가적고, atorvastatin과는달리 rosuvastatin은심혈관질환병력자들에대한일차연구종료점의감소효과가증명된바없으며단지 A Study To Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coreonary Atheroma Burden 연구등에서대리표지자로서 2년간의 40 mg/day 투여로죽상경화반의퇴축이증명된수준임을유념해야겠다 [13-15]. 2. 제2군 : 상위군에해당되지않고저밀도지단백콜레스테롤수치가 190 mg/dl 이상인경우제2군은 20세이상의성인에서 LDL-C 수치가 190 mg/dl 이상인경우로, 죽상경화성심혈관질환의평생위험도가높 이상적인혈중콜레스테롤조절지침 : 2013 년 ACC/AHA 권고안분석 859
은군으로분류되며가족성고콜레스테롤혈증이포함된다. 약 39 mg/dl (1 mmol) 의 LDL-C 수치감소는죽상경화성심혈관질환의위험도를약 20% 가량낮출수있는것으로알려져있으며 [16] 생활습관교정과함께고강도스타틴치료를통한 LDL-C의강하가권유된다. 제2군은 1차예방의범주에속하며 LDL-C 수치이외기타위험인자들의유무가다양한이소성이높은집단으로서고강도스타틴의예방효과는예상되나경우에따라비용대비효용성이가장낮을수도있는집단으로판단된다. 가령기타위험인자들이없는비당뇨여성인경우라면 ( 고강도 ) 스타틴의효용성의증거력이가장약하다. 제2군이하의하위군에서는뇌심혈관질환의병력이없는 1차예방이므로스타틴의효과가부작용을능가하는효용을보일것인지를더욱적극적으로고려하며, 약물투여결정에앞서간기능 (alanine aminotransterase sterase, ALT수치등 ) 을확인하여정상치의 3배이상증가한경우스타틴의사용제한을고려한다. 또한 2차성이상지혈증여부를반드시검증하여야하므로중성지방이 500 mg/dl 이상인복합형이상지혈증인지, 유전적이상지혈증인지를검토하여야한다. 이군에서스타틴에도충분한 LDL-C의강하를얻을수없다면지침에서는비스타틴지질강하약제의사용이필요할수있다. 또한 75세이상의증거력이약한고령에서는한단계이하용량의스타틴이권유된다. 3. 제3군 : 상위군에해당되지않은당뇨 40세에서 75세사이의제1형또는제2형당뇨환자의경우스타틴치료가뇌심혈관위험도를낮출수있을것이라유추되어최소한중강도이상의스타틴치료가권고된다. Collaborative Atorvastatin Diabetes Study연구와같은경우는중강도에해당하는 atorvastatin 10 mg의저용량투여로도당뇨상태에서의심혈관질환의예방을보여주어 [17] 이와같이권고되지만, 아래에서언급하게될 10년내죽상경화성심혈관질환발생위험이 7.5% 이상이면고강도의스타틴치료를권고하고있다. 같은당뇨상태라하더라도 10년내의죽상경화성심혈관질환발생위험의고저에따라위험성을차등화하는접근은이전의지침에비하여개선된 점이라고할수있으나뇌심혈관질환이없으면서콜레스테롤이아주높지않은상태의당뇨에게고강도에해당하는스타틴의효용성이증명된독립적인연구는아직없다. 40세미만과 75세이상의당뇨는증거력이적으므로죽상경화성심혈관질환자의위험도를종합적으로고려하여 ( 하기제4군참조 ) 대상자와의상담을통하여스타틴치료의강도를결정하도록하고있다. 고강도스타틴의장기사용에서증가할수있는당뇨의발생에대한중요성을고려하는데모든스타틴이해당될수있으나 rosuvastatin의경우용량의존적으로당뇨의발생이증가하는것이보고가되므로 [18,19] 사용시유념하여야겠다. 고강도및중등도스타틴의사용으로인한연간당뇨의발생위험은 1,000명당각각 0.33 및 0.11명으로추정된다. 4. 제4군 : 상위군에해당되지않으며 10년내죽상경화성심혈관질환의발생이 7.5% 이상으로높은경우뇌심혈관질환이나당뇨가없는 40-75세사이, LDL-C 이 70-189 mg/dl 인집단의경우 10년내죽상경화성심혈관질환위험도를계산하여스타틴치료시작여부를결정한다. 이번진료지침의괄목한부분중의하나인 Pooled Cohort Equations (see http://my.americanheart.org/ cvriskcalculator and http://www.cardiosource.org/ science-and-quality/practiceguidelines-and-qualitystandards/2013-prevention-guideline-tools.aspx for risk equations) 는 10년내죽상경화성심혈관질환의위험도를예측하여스타틴치료의시작여부결정의지침이되는방법이다. 죽상경화성심혈관질환위험도의상대적인감소 (% reduction) 효과는남녀동등할것으로판단되나인종간의차이는존재하는것으로보아야할것으로보인다. 즉한국인과같은아시아인은백인과같은알고리즘을사용함으로써위험도의과대평가또는해당군에대한스타틴효과의과대평가가능성이존재한다는점을유념해야겠다. 이 Pooled Cohort Equation은최근발표된 5개의 NHLBI (National Heart, Lung, and Blood Institute) 기반의종적인구코호트를종합하여개발되었는데, 첫심근경색의발생, 심혈관질환으로인한사망, 치명적또는비치명적뇌 860 대한의사협회지
Choi HI Han KH Cholesterol management guideline update Diabetes or LDL-C 190 mg/dl No atherosclerotic vascular disease 40-75 years No coronary artery disease No stroke/transient ischemic attack No peripheral artery disease Lifestyle changes and statins 졸중의위험도를성별, 연령, 인종, 총콜레스테롤, HDL-C, 수축기혈압, 고혈압치료제복용여부, 당뇨, 흡연등을분 석인자로하여계산하도록설계되었다. 스타틴을이미복 용하고있는고위험군의포함으로인한위험도과대평가가 능성이보고는되었으나 [20,21], 대체적으로이새로운위 험도예측모델은위험도과대평가로인한문제의소지가 뇌심혈관질환위험의감소기대효과보다는높지않을것으 로판단되어사용가능할것으로판단되지만추후의개정여 부를지켜볼필요가있다. 제 4 군의정의에상응하는대상군 의 LDL-C 기저수치는최소 70 mg/dl 이상일것으로예상 되며기저치의고저에따른죽상경화성심혈관질환예방효 과의차이는나타나지않는다. 10-year ASCVD risk (Pooled Cohort Equations) 7.5 % 5%-7.5% a) < 5% Reassess 10-year ASCVD in 4-6 years Figure 2. Statin therapy in patients without clinical atherosclerotic cardiovascular disease (ASCVD). Potentiate statin therapy if low-density lipoprotein cholesterol (LDL-C) >100 mg/dl after statin therapy 1) subclinical atherosclerosis, 2) overt family history of dyslipidemia or ASCVD, and 3) high CRP levels 2 mg/dl. a) Consider risk-benefit and needs patients agreement. 이외 10 년내죽상경화성심혈관질환자의발생이 7.5% 미만, 21-39 세또는 75 세이상의경우는증거력이미약하 여스타틴치료로명확한이득을얻을수있는군에포함되 지않는다. 이러한대상자에게는임상의사의지식, 경험, 기술과함께환자의선호도등을종합적으로판단하여스타 틴치료의시작을고려할수있다. 제 4 군에서권고되는스 타틴은 40-75 세의대상자들에게는중강도나고강도의스 타틴치료이다. 중강도또는고강도의스타틴치료에따른 부작용의발생은다음과같이예측되며뇌심혈관질환의예 방효과를넘어서지는않는다. 당뇨의연간발생률은스타 틴치료의강도에따라다르게나타나며양의상관관계를 보여중강도스타틴치료시 1,000 명의스타틴사용자중 0.1건, 고강도스타틴치료시 0.3건으로알려져있다. 그러나스타틴에의한뇌심혈관질환위험도감소가더욱크다고믿어지며당뇨발생의경우이유가합당하다면스타틴을끊지말고제반위험도를조절하고비약물요법을극대화하도록권고하고있다. 근병증과출혈성뇌졸중역시각각 1,000명의스타틴사용자중 0.01건정도로발생하여스타틴치료의이득을능가하는위험도를가지고있지는않는것으로판단된다. 10년이내뇌심혈관질환의발생이 5.0-7.5% 라면 1차성으로 LDL-C이 160 mg/dl 이상으로높거나다른유전성고지혈증의증거가있는경우, 1차친족중남자 55세미만, 여자 65세미만에서발생한조기뇌심혈관질환의가족력, 고민감도 C-반응성단백질 2 mg/l 이상인경우, 관상동맥칼슘수치 300 Agatston units 이상이거나연령 성별 인종을보정한정상치의 75 백분위수이상인경우, 발목상완지수 0.9 미만, 일생동안죽상경화성심혈관질환의위험이높은경우와같은인자들의존재여부에따라스타틴의치료여부를고려한다. 40세미만의젊은대상군은위험도예측모델이정확치않으며, 40-59세의대상에게는 10년위험도이외에평생위험도를측정하여고려한다. 이군의경우고강도의스타틴치료에서는부작용의우려가효용을앞설수있으나중강도의스타틴치료의경우는효용이앞설것으로예상된다. 안정성 스타틴치료를결정하기앞서스타틴치료에따른위험이높아질수있는상황을잘인지하고있어야한다. 이번진료지침에서강조된바와같이스타틴치료는효용이부작용을능가하는경우에만개시 유지하여야하며, 환자가 75세이상의고령인경우, 신장간장기능을포함한다발성장기기능저하, 근육병증및스타틴부작용의병력, ALT가정상상한치의 3배초과상승수치를보이는경우, 약물의다제복용, 출혈성뇌졸중병력, 아시아인종, 최대용량의스타틴복용 ( 특히 simvastatin) 시에는각별한주의가필요하 이상적인혈중콜레스테롤조절지침 : 2013 년 ACC/AHA 권고안분석 861
며용량을한단계낮추어시작한다. 이러한경우이외에는일반적으로스타틴의안정성은매우높기때문에본지침은 creatine kinase (CK) 수치는복용중주기적으로측정할필요는없으며, 근병증의위험이높을것으로판단되는대상에게기저치를측정하는것을권고하고있다. ALT는기저치및스타틴치료중간독성의증상이의심될때측정한다. 하지만 ALT수치역시 CK수치와마찬가지로주기적인측정이더이상권고되지는않는다. 비약물요법및비스타틴치료 스타틴치료와병행하여지속적으로생활개선등의비약물요법을추구하여야한다. 2013년 ACC/AHA에서는운동및식이에대한지침도같이발표되었는데 [6], 그내용을매우간단히요약하면운동및저염식은주로혈압의조절효과가크게나오며, 탄수화물, 포화지망및트랜스지방을불포화지방및단백질로하루칼로리의 10% 치환시키면이상지질혈증의개선이이루어지는것으로정리할수있다. 스타틴의효과를모니터하기위하여서는 LDL-C 수치의측정이필요하다. 즉 LDL-C 수치는스타틴복용의결과를확인하며복용순응도를보기위한지표로서사용하며더이상죽상경화성심혈관질환발생예방의지표로서해석하지않는다는것이다. 제제최초투여후 4-12주사이에그효과를확인하며이후에는 3-12개월마다확인한다. 상기알고리즘의적용으로대부분의대상자에게서 LDL-C 100 mg/dl 미만의수치에도달하는결과를볼것으로예상한다. 스타틴치료중측정한 LDL-C 수치가연속 2회이상 40 mg/dl 미만이라면스타틴의용량을한단계완화하여야한다. 비스타틴제제의단독또는스타틴과의병합사용에따른뇌심혈관질환위험도의감소를증명하는단독증거는부족한실정이다. 즉비스타틴제제의사용으로낮아진 LDL-C 수치는스타틴의고용량에의한효과에비교하였을때에효용성의증거력이부족하다고판단하였다. 이에금번진료지침에서는고위험군의환자가스타틴에대한반응이낮거나견디지못하는경우, 또는충분한노력에도불구하고효과가기대 에미치지못하는경우, 그리고약제부작용및약물상호작용을염두에두고비스타틴제제를추가할수있는것으로명기하고있다. 기타고려사항 진행된심부전 ( 뉴욕심장학회분류 II-IV) 이나투석중인신부전환자의경우스타틴의효용성이증명되지않은군으로스타틴을시작하지도중단하지도않는다 [22-24]. 스타틴의복용중당뇨가발생하였다면생활요법의극대화로뇌심혈관질환의예방을최대화하며, 기타부작용이없다면스타틴용량을줄일당위성은없다. 75세이상의고령대상자들은뇌심혈관질환의병력이있다면한강도낮춘중강도스타틴을복용하지만, 뇌심혈관질환의병력이없는경우의증거력은약하다. 따라서기왕에복용중인스타틴에잘적응할때는계속유지하는반면복용을시작하는데있어서는효용이외의부작용, 대상자의확신등을고려하여결정한다. 40세미만의젊은대상자에게서는일생동안뇌심혈관질환의위험이존재하는대상에유의하여야하는데인간면역결핍바이러스에감염된자, 류마티스성혹은염증성질환이있는자, 또는고형장기이식을받은환자, 유전적이상지혈증이있는경우등이해당된다. 가족성고콜레스테롤혈증의경우 LDL-C이매우높은경우가많고스타틴의복용으로도 LDL-C의저하에제한이존재한다. 그렇지만상기알고리즘의적용으로스타틴을근거로한조절을시도한다면복용후 LDL-C 수치의조절이불충분하여보이더라도반드시죽상경화성심혈관질환의예방실패를의미하는것은아니라고판단한다. 단이러한상태에서의 cholesterol absorption inhibitor 등은이후추가를결정할수있겠다. 만일뇌심혈관질환의병력이있는대상에게고강도스타틴을복용한후 LDL-C이여전히 70 mg/dl 초과하는경우에는 LDL-C 절대수치가더이상예방효과를가늠하는지표가아니므로추가적비스타틴제제의추가를꼭고려하지않아도된다. 단 fenofibrate의경우 ACCORD 연구 [25] 에서높은중성지방및낮은 HDL-C 862 대한의사협회지
Choi HI Han KH Cholesterol management guideline update 수치를보이는당뇨환자에게추가복용으로죽상경화성심혈관질환의예방효과를나타내었지만고강도스타틴치료보다동등또는우월한지의증명은이루어지지않았다고주장한다. 스타틴치료비대상자의경우 ( 알고리즘을거쳐심혈관질환 당뇨가아직은없고뇌심혈관질환위험이 7.5% 미만인경우 ) 측정된위험도가 5% 이상일경우는대상자가높은순응도와안정성으로복용을할수있고기타위험도를고려할때스타틴의효용이예상된다면복용을시작할수있다. 그렇지않다하더라도향후 4-6년마다 1회이상위험도를재검토하여장기계획을수립하도록한다. HDL-C, non HDL-C의경우그임상적의의가축소되었으나전혀의미가없다고볼수는없으며향후발표될여러임상연구에따라그중요성이제고될여지는충분하다. 본지침에서는 LDL-C 수치의강하정도및모니터등의가치를원용할수밖에없으므로기존지침과의상보적해석이필요할것으로판단된다. 결론 이번 2013년 ACC/AHA 혈중콜레스테롤치료지침의경우기존에발표된연구결과중에서도가장확고한근거수준을가지고있는결과만을토대로작성되었기때문에, 기존에알려진증거로는충분한해법을찾을수없는부분도있다. 이에대해추가적인연구가더필요할것으로생각되며, 대표적인분야들로는 75세이상의고령자에서뇌심혈관질환의 1차예방효과, 고위험군환자에서스타틴용법의차이 ( 특정콜레스테롤수치에따른스타틴용량조절대고정스타틴용량의사용 ) 에따른결과비교연구, 권고되는스타틴용량을복용할수없는대상자에서비스타틴제제의추가복용, 스타틴치료와연관되어발생하는당뇨에대한전반적연구, 새로운지질조절제에대한연구등이그것이다. 찾아보기말 : 진료지침 ; 콜레스테롤 ; 심혈관질환위험도 ; 스타틴 ORCID Hyo-In Choi, http://orcid.org/0000-0002-6216-0873 Ki Hoon Han, http://orcid.org/0000-0002-6117-3787 REFERENCES 1. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Judd SE, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Mackey RH, Magid DJ, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER 3rd, Moy CS, Mussolino ME, Neumar RW, Nichol G, Pandey DK, Paynter NP, Reeves MJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Wong ND, Woo D, Turner MB; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics: 2014 update. A report from the American Heart Association. Circulation 2014;129:e28-e292. 2. 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. 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. 3. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). 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. 4. Graham R; US Institute of Medicine. Committee on Standards for Developing Trustworthy Clinical Practice Guidelines. Clinical practice guidelines we can trust. Washington, DC: National Academies Press; 2011. 5. European Association for Cardiovascular Prevention & Rehabilitation, Reiner Z, Catapano AL, De Backer G, Graham I, Taskinen MR, Wiklund O, Agewall S, Alegria E, Chapman MJ, Durrington P, Erdine S, Halcox J, Hobbs R, Kjekshus J, Filardi PP, Riccardi G, Storey RF, Wood D; ESC Committee for Practice Guidelines (CPG) 2008-2010 and 2010-2012 Committees. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 2011;32:1769-1818. 이상적인혈중콜레스테롤조절지침 : 2013 년 ACC/AHA 권고안분석 863
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Choi HI Han KH Cholesterol management guideline update 23. Fellstrom BC, Jardine AG, Schmieder RE, Holdaas H, Bannister K, Beutler J, Chae DW, Chevaile A, Cobbe SM, Gronhagen- Riska C, De Lima JJ, Lins R, Mayer G, McMahon AW, Parving HH, Remuzzi G, Samuelsson O, Sonkodi S, Sci D, Suleymanlar G, Tsakiris D, Tesar V, Todorov V, Wiecek A, Wuthrich RP, Gottlow M, Johnsson E, Zannad F; AURORA Study Group. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med 2009;360:1395-1407. 24. Sharp Collaborative Group. Study of Heart and Renal Protection (SHARP): randomized trial to assess the effects of lowering low-density lipoprotein cholesterol among 9,438 patients with chronic kidney disease. Am Heart J 2010;160:785-794. 25. ACCORD Study Group, Ginsberg HN, Elam MB, Lovato LC, Crouse JR 3rd, Leiter LA, Linz P, Friedewald WT, Buse JB, Gerstein HC, Probstfield J, Grimm RH, Ismail-Beigi F, Bigger JT, Goff DC Jr, Cushman WC, Simons-Morton DG, Byington RP. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med 2010;362:1563-1574. Peer Reviewers Commentary 콜레스테롤혈증의치료목표는혈중콜레스테롤을낮춤으로써장기적인심혈관질환발병률을낮추는것이다. 고지질혈증진료권고안은 2001년 ATP-III 이후 12년만인 2013년 11월에미국심장학회 (ACC/AHA) 에서새로발표되었다. 임상적증거에따라서치료방법과위험군분류에많은변화가있었고특히가장중요한약제인스타틴의사용기준이임상현장에적용하기쉽도록크게변경되었다. 본논문의가장큰의의는새로운권고안을한국인고콜레스테롤혈증의진료에반영하기위해서필요한권고안의임상적배경및의학적증거의정도에대하여체계적으로재검토한것이다. 본논문은주로스타틴의사용기준에대하여기술하고있으며, 임상현장에서는본논문의내용과함께비약물요법에대한치료를병행하는것이바람직할것이다. [ 정리 : 편집위원회 ] 이상적인혈중콜레스테롤조절지침 : 2013 년 ACC/AHA 권고안분석 865