Singh Vibhuti, Deedwania Prakash
University of South Florida, College of Medicine and Suncoast Cardiovascular Center, St Petersburg, FL, USA.
Drugs Today (Barc). 2008 Jun;44(6):455-71. doi: 10.1358/dot.2008.44.6.1217468.
Atherosclerosis, especially when manifested as coronary artery disease (CAD), continues to be the number one cause of mortality and morbidity in developed nations and will soon become so in developing countries. Survivors of an acute heart attack have an increased risk of illness and death that is 1.5-15 times greater than in the general population. Sudden death occurs in myocardial infarction (MI) survivors at a rate 4-6 times greater than in the general population. After an initial recognized MI, 25% of male and 38% of female survivors die within 1 year. Within 6 years after a recognized MI, 18% of men and 35% of women will have a second MI, 7% of men and 6% of women will suffer sudden death, and 22% of men and 46% of women will be disabled with heart failure. Aggressive secondary prevention, therefore, is the key to containing and reversing the "malignant" natural history of CAD, since patients with CAD or CAD risk equivalents are already in the "high risk" category according to the Adult Treatment Panel III (ATP III) of the National Cholesterol Education rogram (NCEP). Treatment of dyslipidemia, especially the reduction of low-density lipoprotein (LDL) cholesterol levels to below 100 mg/dl, was recommended by the 2001 NCEP-ATP Guidelines. In 2004, based on the increasing evidence from several major clinical trials between 2001 and 2004, the NCEP-ATP reaffirmed its LDL goal of < 100 mg/dl in patients with CAD or coronary disease risk equivalents (including multiple risk factors), with an optional LDL goal of < 70 mg/dl in very-high-risk patients (including patients with established coronary heart disease plus other highrisk conditions) Findings from major studies, such as the Treating to New Targets (TNT) study, the Scandinavian Simvastatin Survival Study (4S), the Collaborative Atorvastatin Diabetes Study (CARDS), the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial and, more recently, the Lipid-Lowering Arm of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-LAA), lend support to the idea that greater LDL cholesterol lowering than that achieved with standard doses of statins may be warranted in patients with CAD and metabolic syndrome, CAD and diabetes, CAD and congestive heart failure, and CAD and renal insufficiency. On the other hand, additional lipid reduction may also be warranted in patients with risk factors such as diabetes, hypertension or a history of stroke, but without manifest CAD and despite relatively normal cholesterol levels. These newer indications for statins, atorvastatin in particular, as part of more aggressive secondary and primary prevention, are reviewed in this paper.
动脉粥样硬化，尤其是表现为冠状动脉疾病（CAD）时，仍然是发达国家发病和死亡的首要原因，并且在发展中国家也将很快成为首要原因。急性心脏病发作的幸存者患病和死亡风险增加，比普通人群高1.5至15倍。心肌梗死（MI）幸存者的猝死发生率比普通人群高4至6倍。在首次确诊心肌梗死后，25%的男性幸存者和38%的女性幸存者会在1年内死亡。在确诊心肌梗死后6年内，18%的男性和35%的女性会再次发生心肌梗死，7%的男性和6%的女性会猝死，22%的男性和46%的女性会因心力衰竭而致残。因此，积极的二级预防是控制和逆转CAD“恶性”自然病程的关键，因为根据国家胆固醇教育计划（NCEP）的成人治疗小组III（ATP III），CAD患者或具有CAD风险等同因素的患者已属于“高危”类别。2001年NCEP-ATP指南建议治疗血脂异常，特别是将低密度脂蛋白（LDL）胆固醇水平降至100mg/dl以下。2004年，基于2001年至2004年间几项主要临床试验不断增加的证据，NCEP-ATP重申了其对CAD患者或具有冠心病风险等同因素（包括多种危险因素）的LDL目标<100mg/dl，对于极高危患者（包括已确诊冠心病加其他高危情况的患者），LDL目标可选择<70mg/dl。一些主要研究的结果，如强化降脂治疗新目标（TNT）研究、斯堪的纳维亚辛伐他汀生存研究（4S）、阿托伐他汀协作糖尿病研究（CARDS）、积极降低胆固醇水平预防卒中（SPARCL）试验，以及最近的盎格鲁-斯堪的纳维亚心脏结局试验降脂分支（ASCOT-LAA），都支持这样一种观点，即对于CAD和代谢综合征、CAD和糖尿病、CAD和充血性心力衰竭以及CAD和肾功能不全的患者，可能需要比标准剂量他汀类药物更大程度地降低LDL胆固醇。另一方面，如果患者有糖尿病、高血压或卒中病史等危险因素，但无明显CAD且胆固醇水平相对正常，也可能需要进一步降低血脂。本文将对他汀类药物，特别是阿托伐他汀，作为更积极的二级和一级预防一部分的这些新适应证进行综述。
