Mechanisms And Protective Effect Of Teprenone Against Antiplatelet Drugs-induced Gastric Mucosal Damage

Objectives:(1) To evaluate the mechanisms and protective effect of teprenone and pantoprazole against antiplatelet drugs-induced gastric mucosal damage in patients with coronary vesscular disease (CVD).(2) To investigate the influence of teprenone and pantoprazole on the antiplatelet effect of clopidogrel and aspirin in patients with CVD.Methods:A total of 105 patients with coronary heart disease and younger than age 70 years, who needed to receive dual anti-platelet therapy of asprin and clopidogral were randomly divided into three groups. Each group contained 35 patients. The patients with peptic ulcer or digestive haemorrhage history, prescribing other NSAIDs, anticoagulant drugs or glucocorticoid simultaneously were excluded to the study. On the base of their own therapy, the patients in control group didn't receive any gasric protective therapy. The patients in teprenone group were prescribed teprenone (50mg tid) for 30 days and the patients in pantoprazole group were prescribed pantoprazole (40mg qd) for 30 days . TXB2,6-Keto-PGF1α,ET-1,palatelet aggregation(ADP revulsant) and fecal occult blood were measured before and after the treatment. The gastric-intestinal symtoms and occur of gastric-intestinal haemorrhage, cardiovascular event were recorded during and after the treatment..Results:Totally 80 patients completed the study, among which, 26 persons belonged to control group, 30 and 24 patients were in teprenone and pantoprazole group, respectively. The other 25 patients were excluded as the reason of drug discontinuance, surpassing the time of follow-up visit and so on.(1) ET-1 level: In the control group, the ET-1 levels were 102.34±17.00 ng/L and 103.19±17.21 ng/L before and after treatment, no significant variance was found between them (t=-0.287,P=0.777). In the teprenone group, the ET-1 levels were 96.61±16.41 ng/L before and 74.66±21.02 ng/L after treatment, there was a significant difference between them. (t=8.602, P<0.001). In the pantoprazole group, the levels were 103.86±25.84 ng/L before and 99.18±24.01 ng/L after treatment. No significant difference was found (t=1.178, P=0.251).(2) 6-Keto-PGF1αlevel: In the control group, the 6-Keto-PGF1αlevels were 40.88±17.18 ng/L before and 39.42±17.02 ng/L after treatment, no significant difference was found between them (t=0.383, P=0.705). In the teprenone group, these levels were 39.59±13.65 ng/L and 47.05±15.63 ng/L. The 6-Keto-PGF1αlevels increased significantly after the treatment (t=-3.268,P=0.003). In the pantoprazole group, the levels were 38.28±15.57 ng/L before and 34.68±14.08 ng/L after treatment, there was no significant difference between them (t=1.420,P=0.169).(3) TXB2 level: In the control group, the TXB2 levels were 106.50±28.67 ng/L before and 102.23±26.55 ng/L after treatment. No significant difference was found (t=0.934,P=0.359). In the teprenone and the pantoprazole group, the levels were 122.64±40.23 ng/L, 113.81±46.43 ng/L before treatment and 116.55±34.79 ng/L, 104.85±40.75 ng/L after treatment. No significant difference was found between them(teprenone group, t=0.719,P=0.478; pantoprazole group, t=1.465, P=0.157).(4) TXB2/ 6-Keto-PGF1α:In the control group , the ratio were 3.49±2.19 before and 3.97±1.93 after treatment, no significant difference was found(Z=0.185) between them; In the teprenone group , the ratio were 4.09±2.29 before and 3.06±0.96 after treatment. The ratio reduced significantly after treatment(Z=0.001). In the pantoprazole group ,the ratio were 3.76±2.59 before treatment and 4.15±1.60 after treatment, no significant difference was found between them.(Z=0.612)(5) Palatelet aggregation (ADP revulsant): No significant difference was found between before and after treatment in all three groups. The values were control group(t=1.779,P=0.087), teprenone group (t=-0.891, P=0.380) and pantoprazole group (t=0.933,P=0.361), respectively.(6) Compared to control group, both teprenone and pantoprazole group had a lower incidence of gastric intestinal symptoms(P=0.048). The symtoms included abdominal pain, abdominal distention, acid regurgitation, heartburn, abdomial discomfort, diarrhea, nausea and vomiting. Patients in all three groups had a negative result in fecal occult blood measure. No gastric-intestinal haemorrhage and cardiovascular event were found in all three groups. Conclusion:(1) Teprenone can protect the gastric mucosa by increasing the production of PGI2 and ET-1. in CVD patients who need to receive dual antiplatelet therapy. But it doesn't affect the blood level of TXA2.(2) Pantoprazole doesn't affect the blood levels of PGI2,TXB2 and ET-1 in patients with coronary heart diease who received dual anti-platelet theray.(3) Teprenone may benefit to CVD patients by reduing the TXB2/6-Keto-PGF1αratio.(4) Both teprenone and pantoprazole don't affect the anti-platelet effect of clopidogrel and aspirin.(5) Teprenone and pantoprazole can reduce the incidence of gastric-intestinal symptoms in these patients. The patients with low risk of gastric-intestinal haemorrhage have a low incidence of gastric-intestinal haemorrhage in the first month of dual anti-platelet therapy...