阿托伐他汀对高脂血症患者血小板聚集反应的影响

Effect of Atorvastatin Treatment on Platelet Aggregation in Whole Blood in the Patients with Hypercholesterolaemia

观察降血脂药阿托伐他汀作用于高脂血症患者的血小板聚集反应。测试全血血小板聚集对各种诱导剂的反应性及实验的重复性 ,并选择胶原作为诱导剂进行全血血小板聚集反应检测。 30个高脂血症患者接受为期16周的治疗 ,用药剂量递增 ,从每日用药 10、2 0、40mg ,到 80mg ,均分别用药 4周 ,直至患者血脂水平达到靶水平以下。分别在最大剂量用药期及停药后 4周检测患者的血小板聚集反应、血小板计数、平均血小板体积、总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇及甘油三酯水平。总胆固醇、低密度脂蛋白胆固醇及甘油三酯水平在停药后显著回升 (5 .0± 1.1、3.0± 1.0、2 .2± 3.3mmol/L比 9.0± 3.1、6 .8± 1.5、5 .0± 12 .4mmol/L ,P <0 .0 0 1)。与停药后 4周相比 ,在最大剂量用药期 ,患者全血血小板聚集反应显著降低 (自 19.0± 3.1Ω降至 17.1± 4.6Ω ,P <0 .0 5 ) ,而高密度脂蛋白胆固醇、血小板计数及平均血小板体积不受影响。表明阿托伐他汀能有效降低高脂血症患者的血脂水平及改善血小板聚集功能。

Aim To investigate the effect of the new potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, atorvastatin, on platelet aggregation in Chinese patients with hypercholesterolaemia. Methods Four agonists to induce platelet aggregation in whole blood were tested in normal subjects. The platelets showed good response to collagen in vitro but poor response to adenosine diphosphate (ADP) and adrenaline. The aggregation response to collagen 1.0 and 2.5 mg/L was assessed in 30 patients who had been receiving atorvastatin for 16 weeks, titrated at 4-week intervals through 10, 20, 40 and 80 mg daily until target low density lipoprotein cholesterol (LDLC) levels were achieved. Results The tests were repeated 4-weeks after stopping therapy. Withdrawal of atorvastatin resulted in the expected increases (all P<0.001) in total cholesterol (TC), triglycerides (TG) and LDLC from 5.0±1.1, 2.2±3.3, 3.0±1.0 mmol/L to 9.0±3.1, 5.0±12.4, 6.8±1.5 mmol/L respectively without significant change in high density lipoprotein cholesterol. Platelet count and volume remained unchanged after cessation of therapy and the slope and magnitude of the platelet aggregation curve in response to collagen 1.0 mg/L was unchanged whereas the amplitude of the response to collagen 2.5 mg/L increased from 17.1±4.6 Ω to 19.0±3.1 Ω without change in slope. Conclusion We concluded that atorvastatin treatment produced large reductions in TC, LDLC and TG, and that the only change seen in whole blood platelet aggregation was a small but significant reduction in the amplitude of the response to collagen 2.5 mg/L.