普罗布考联合降脂药物对动脉粥样硬化病人的干预治疗

目的 探讨普罗布考、阿司匹林、阿托伐他汀(PAS)联合应用对动脉粥样硬化病人的干预作用.方法 入选436例冠心病病人分为对照组(阿司匹林100 mg/d和阿托伐他汀10 mg/d)和PAS组(普罗布考0.25 g/d,阿司匹林100 mg/d,阿托伐他汀10 mg/d).另有颈动脉粥样硬化病人38例,均经PAS疗法治疗1年.测定治疗前后血清氧化低密度脂蛋白(ox-LDL),基质金属蛋白酶-9(MMP-9)水平.超声检测治疗前后颈动脉厚度及斑块变化,统计发生的心血管事件.结果 最终纳入试验病例为378例,其中对照组201例,PAS组177例.对照组治疗前后ox-LDL及MMP-9水平无明显变化(P>0.05).PAS组治疗后ox-LDL较治疗前下降了31.7%(16.13±0.02)mmol/L比(23.46±0.01)mmol/L,P<0.05],MMP-9较治疗前下降了42.4%(4.19±0.02)mmoL/L比(7.15±0.01)mmol/L,P<0.05)].对照组再入院率、心绞痛再发率、心肌梗死发生率、病死率分别为23例(11.4%)、28例(13.9%)、4例(2.0%)、2例(1.0%),PAS组有明显下降分别为6例(3.4%)、13例(7.3%)、1例(0.6%)、0例(P<0.05).PAS组治疗后颈动脉内膜厚度(0.097±0.001)cm比(0.248±0.001)cm]、斑块厚度(0.103±0.002)em比(0.209±0.002)cm,P<0.05)],较治疗前均有明显下降.结论 联合应用普罗布考对血清ox-LDL及MMP-9有明显的抑制作用,对动脉粥样硬化的形成,具有明显的干预作用.

Effects of probucol, aspirin and atorvastatin combination therapy upon atherosclerosis

Objective To investigate the effects of probueol, aspirin and atorvastatin (PAS) combination therapy upon atherosclerosis. Methods A total of 436 patients with coronary artery disease were selected and randomly divided into control group (aspirin 100 mg, atorvastatin 10 mg daily) and PAS group (aspirin 100 mg, atorvastatin 10 mg and probucol 0.25 g daily). After a 1-year treatment course, 378 cases remained in the study (201 in control group vs. 177 in PAS group). These patients were followed for throughout the study course and their serum levels of high density lipoprotein (HDL), ox-LDL, TXB2 and MMP-9 were measured at 6 and 12 months respectively. Twenty cases were diagnosed with carotid artery plaque by carotid ultrasound and 16 cases remained in the PAS group. They were followed with ultrasound for plaque thickness. Results In the control group, the pre-treatment level of MMPs and ox-LDL were not statistically different from the post-treatment level (P > 0.05). In the PAS group, the pre-treatment level of ox-LDL was (23.46±0.01) mmol/L and the post-treatment level (16.13±0.02) mmol/L. There was a decrease of 31.7% (P < 0.05). The pre-treatment level of MMPs and MMP-9 in the control group was not statistically different from the post-treatment level The pre-treatment level of MMP-9 in the PAS group was (7.15±0.01)mmol/L and the post-treatment level(4.19±0. 02) mmol/L There was a decrease of 42.4% (P < 0.05). During the course of follow-up, the hospitalization rate, angina recurrence rate, myocardial infarction rate and mortality rate for the control group were 23 (11.4%), 28 (13.9%), 4 (2.0%) and 2 (1.0%) respectively. In the PAS group, the corresponding values were 6 (3.4%), 13 (7.3%), 1(0.6%) and 0 respectively. All parameters of adverse events showed a significant decrease in the PAS group(P <0.05). Among the cases with carotid plaque, the pretreatment measurements of intima thickness and plaque thickness were(0.103±0.002)cm and (0.248±0.001)cm while the post-treatment corresponding measurements (0.097±0.001) cm and (0.209 ±0.002) cm respectively. There was a significant difference between the PAS group and the control group (P < 0.05). Conclusion Antioxidant probucol significantly inhibits the generation of ox-LDL and MMP-9. PAS therapy also reduces the plaque thickness and decreases the rate of adverse event in patients with atherosclerosis. Antioxidants can be considered as a new adjunct therapy in the treatment of atherosclerosis.