Kadikoylu Gurhan, Yukselen Vahit, Yavasoglu Irfan, Bolaman Zahit
Department of Internal Medicine, Division of Haematology-Oncology, Medical School, Adnan Menderes University, Aydin, Turkey.
Ann Pharmacother. 2003 Apr;37(4):478-84. doi: 10.1345/aph.1C189.
To compare the effects of simvastatin and atorvastatin on hemostatic parameters.
Sixty-one patients with primary hypercholesterolemia without coronary heart disease were treated with atorvastatin 10-20 mg/d or simvastatin 10-20 mg/d. At baseline, 4, 12, and 24 weeks, lipid levels such as low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), very-low-density lipoprotein cholesterol (VLDL-C), triglycerides (TGs), and hemostatic parameters such as platelet counts, partial thromboplastin time (PTT) prothrombin time (PT), and fibrinogen levels were measured.
At 12 weeks, the doses of the statins were increased to 20 mg/d in 10 of 35 (28.5%) patients treated with atorvastatin and 18 of 26 (69.2%) patients treated with simvastatin when the target level of LDL-C (130 mg/dL) was not reached. Mean doses were atorvastatin 12.8 mg/d and simvastatin 16.9 mg/d. After 24 weeks, 5 patients (14.3%) in the atorvastatin group and 4 patients (15.3%) in the simvastatin group had not reached the goal. In patients with diabetes, target level (LDL-C <100 mg/dL) was not reached in 35.7% of patients in the atorvastatin group and 44.4% of patients in the simvastatin group. Both simvastatin and atorvastatin were effective in lowering TC and LDL-C levels (p < 0.001). Atorvastatin lowered TGs significantly (p < 0.01). Neither atorvastatin nor simvastatin significantly reduced VLDL-C levels. HDL-C levels increased with atorvastatin, but there was no significant difference between the 2 groups. Platelet counts decreased with both statins nonsignificantly. Moreover, fibrinogen levels decreased with simvastatin and atorvastatin, but these reductions were significant only for simvastatin (p < 0.05). We detected prolongation of the PT with both drugs (p < 0.05); however, prolongation of the PTT was significant only with simvastatin (p < 0.001). Effectiveness of both statins on lipid and hemostatic parameters was dose related. Adverse effects were seen in 5 patients (14.2%) treated with atorvastatin and 3 patients (11.5%) treated with simvastatin. Elevations in serum transaminase levels >3 times the upper limit of normal and in creatine phosphokinase >5 times the upper limit of normal were not observed in any group.
Atorvastatin was more effective than simvastatin on lipid parameters, although statistically insignificantly, while simvastatin produced more significant changes than atorvastatin on hemostatic parameters. The mean dose of simvastatin was greater than that of atorvastatin. Both statins had increased effects on lipid and hemostatic parameters when doses were increased. Atorvastatin and simvastatin were well tolerated. Different effects of statins on lipid levels and on coagulation parameters should be considered in patients with hypercholesterolemia and tendency to coagulation, especially in preventing thrombotic events. Further studies in larger trials are needed to confirm these observations.
比较辛伐他汀和阿托伐他汀对止血参数的影响。
61例无冠心病的原发性高胆固醇血症患者接受阿托伐他汀10 - 20mg/d或辛伐他汀10 - 20mg/d治疗。在基线、4周、12周和24周时,测量血脂水平,如低密度脂蛋白胆固醇(LDL-C)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、极低密度脂蛋白胆固醇(VLDL-C)、甘油三酯(TGs),以及止血参数,如血小板计数、部分凝血活酶时间(PTT)、凝血酶原时间(PT)和纤维蛋白原水平。
12周时,阿托伐他汀治疗的35例患者中有10例(28.5%)、辛伐他汀治疗的26例患者中有18例(69.2%)在未达到LDL-C目标水平(130mg/dL)时将他汀类药物剂量增加至20mg/d。平均剂量分别为阿托伐他汀12.8mg/d和辛伐他汀16.9mg/d。24周后,阿托伐他汀组有5例患者(14.3%)、辛伐他汀组有4例患者(15.3%)未达到目标。在糖尿病患者中,阿托伐他汀组35.7%的患者、辛伐他汀组44.4%的患者未达到目标水平(LDL-C <100mg/dL)。辛伐他汀和阿托伐他汀均能有效降低TC和LDL-C水平(p < 0.001)。阿托伐他汀显著降低TGs水平(p < 0.01)。阿托伐他汀和辛伐他汀均未显著降低VLDL-C水平。阿托伐他汀使HDL-C水平升高,但两组间无显著差异。两种他汀类药物均使血小板计数非显著下降。此外,辛伐他汀和阿托伐他汀均使纤维蛋白原水平下降,但仅辛伐他汀的下降具有显著性(p < 0.05)。我们检测到两种药物均使PT延长(p < 0.05);然而,仅辛伐他汀使PTT延长具有显著性(p < 0.001)。两种他汀类药物对血脂和止血参数的有效性与剂量相关。阿托伐他汀治疗的5例患者(14.2%)和辛伐他汀治疗的3例患者(11.5%)出现不良反应。任何一组均未观察到血清转氨酶水平升高超过正常上限3倍以及肌酸磷酸激酶升高超过正常上限5倍的情况。
阿托伐他汀在血脂参数方面比辛伐他汀更有效,尽管在统计学上无显著差异,而辛伐他汀在止血参数方面比阿托伐他汀产生更显著的变化。辛伐他汀的平均剂量大于阿托伐他汀。当剂量增加时,两种他汀类药物对血脂和止血参数的作用均增强。阿托伐他汀和辛伐他汀耐受性良好。对于高胆固醇血症和有凝血倾向的患者,尤其是在预防血栓形成事件时,应考虑他汀类药物对血脂水平和凝血参数的不同影响。需要在更大规模的试验中进行进一步研究以证实这些观察结果。