[Effects of probucol, aspirin and atorvastatin combination therapy upon atherosclerosis].
OBJECTIVE
To investigate the effects of probucol, 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).


CONCLUSIONS
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.
Meng
Xiao-Ping
XP
Department of Cardiology, Second Hospital of Jilin University, Changchun 130041, China.
Wang
Su-Xiang
SX
Zhang
Ji-Chang
JC
Li
Zhen-Xiao
ZX
Geng
Li
L
Yin
Chun-Yuan
CY
D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy*; D000069059:Atorvastatin; D008076:Cholesterol, HDL / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D011341:Probucol / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*
D008076:Cholesterol, HDL; D006538:Heptanoic Acids; D000960:Hypolipidemic Agents; D008077:Lipoproteins, LDL; D011758:Pyrroles; C099252:oxidized low density lipoprotein; D000069059:Atorvastatin; D020780:Matrix Metalloproteinase 9; D011341:Probucol; D001241:Aspirin