Sigurdsson G, Haraldsdottir S O, Melberg T H, Tikkanen M J, Miettinen T E, Kristianson K J
Sjúkrahús Reykjavíkur Fossvogi, Reykjavik, Iceland.
Acta Cardiol. 1998;53(1):7-14.
Inhibitors of HMG-CoA reductase are widely used for the treatment of hypercholesterolaemia and have recently been shown in the Scandinavian Simvastatin Survival Study (4S), to reduce coronary mortality as well as total mortality in CH D patients. Although a couple of studies have already established the efficacy ratio between simvastatin and fluvastatin, one of the newest members of this class, we considered it to be important to verify the comparative efficacy in patients with coronary artery disease in the same type of patients that were included in 4S particularly since the previous studies include rather few patients with CHD, 17-28% only.
Three Scandinavian lipid clinics participated in this randomized double-blind study and enrolled a total of 113 hypercholesterolaemic patients with a profile similar to the 4S patients, i.e. either a history of typical angina pectoris lasting at least three months or a myocardial infarction at least six months before the study and with moderate hypercholesterolaemia, total serum cholesterol between 5.5 and 8.0 mmol/l. After a diet run-in period lasting at least 8 weeks, followed by a two week placebo period, patients received treatment with active drug for a 16 week period, with measurement of lipids using the same technique and laboratory as was used in 4S. Patients were randomly assigned to simvastatin 20 mg or fluvastatin 20 mg. If after 6 weeks of double-blind treatment, the 4S total cholesterol target of < or = 5.2 mmol/l total serum cholesterol had not been reached, the dose was doubled at the next visit, i.e. at week 10 based upon blinded titration information from the central lipid laboratory like in the 4S study. A final assessment of serum lipids and lipoproteins was made at week 16. The mean percent reductions in LDL-cholesterol from baseline were 37% and 40% in the simvastatin group compared to 19% and 26% in the fluvastatin group, at weeks 10 and 16, respectively (p < 0.001). In the simvastatin group 18 percent of the patients needed an increase in the dose to 40 mg compared to 63 percent in the fluvastatin group (p < 0.001). At the 20 mg dosage, simvastatin produced a lowering of LDL-cholesterol approximately twice that of fluvastatin 20 mg and resulted in 82% of patients achieving the cholesterol target levels as defined in the 4S study, compared to 19% for fluvastatin. All other recorded lipid variables showed differences which favoured simvastatin over fluvastatin at comparable doses including serum triglyceride reductions where serum triglycerides at week 6 were borderline significantly different between the two groups. Patient tolerability of the two drugs was similar.
At the recommended doses in patient with angina or a prior MI and mild to moderate hypercholesterolaemia simvastatin is considerably more effective than fluvastatin in lowering serum total cholesterol, LDL-cholesterol as well as other serum lipid risk factors. At an average titrated dose of 32 mg less than 50% of the fluvastatin patients reached the 4S cholesterol target of < 5.2 mmol/l compared to 89% of the simvastatin patients at an average dose of 23 mg daily and only 13% of the fluvastatin patients achieved an LDL-cholesterol reduction of at least 40% compared to 63% of the simvastatin patients.
HMG - CoA还原酶抑制剂被广泛用于治疗高胆固醇血症，最近在斯堪的纳维亚辛伐他汀生存研究（4S）中显示，其可降低冠心病患者的冠状动脉死亡率和总死亡率。尽管已有几项研究确定了辛伐他汀与氟伐他汀（该类药物的最新成员之一）之间的疗效比，但我们认为在4S研究纳入的同一类冠心病患者中验证其比较疗效很重要，特别是因为之前的研究纳入的冠心病患者较少，仅占17 - 28%。
三家斯堪的纳维亚脂质诊所参与了这项随机双盲研究，共招募了113名高胆固醇血症患者，其特征与4S研究中的患者相似，即有至少持续三个月的典型心绞痛病史，或在研究前至少六个月有心肌梗死病史，且患有中度高胆固醇血症，总血清胆固醇在5.5至8.0 mmol/L之间。经过至少8周的饮食导入期，随后是两周的安慰剂期，患者接受活性药物治疗16周，使用与4S研究相同的技术和实验室测量血脂。患者被随机分配接受20 mg辛伐他汀或20 mg氟伐他汀治疗。如果在双盲治疗6周后，未达到4S研究中总血清胆固醇≤5.2 mmol/L的目标，则在下一次就诊时（即第10周）根据中央脂质实验室的盲法滴定信息将剂量加倍，如同4S研究一样。在第16周对血清脂质和脂蛋白进行最终评估。在第10周和第16周时，辛伐他汀组LDL - 胆固醇从基线的平均降低百分比分别为37%和40%，而氟伐他汀组分别为19%和26%（p < 0.001）。辛伐他汀组18%的患者需要将剂量增加至40 mg，而氟伐他汀组为63%（p < 0.001）。在20 mg剂量时，辛伐他汀降低LDL - 胆固醇的幅度约为20 mg氟伐他汀的两倍，并且82%的患者达到了4S研究中定义的胆固醇目标水平，而氟伐他汀组为19%。所有其他记录的脂质变量显示，在相当剂量下，辛伐他汀优于氟伐他汀，包括血清甘油三酯降低情况，在第6周时两组血清甘油三酯的差异接近显著水平。两种药物的患者耐受性相似。
对于患有心绞痛或既往心肌梗死且有轻度至中度高胆固醇血症的患者，按推荐剂量使用时，辛伐他汀在降低血清总胆固醇、LDL - 胆固醇以及其他血清脂质危险因素方面比氟伐他汀有效得多。在平均滴定剂量为32 mg时，不到50%的氟伐他汀患者达到了4S研究中<5.2 mmol/L的胆固醇目标，而辛伐他汀患者平均每日剂量为23 mg时这一比例为89%；只有13%的氟伐他汀患者LDL - 胆固醇降低至少40%，而辛伐他汀患者这一比例为63%。
