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Background: aspirin and clopidogrel antiplatelet therapy in the world-wide use of proton pump inhibitor (PPI) esomeprazole and pantoprazole is most commonly used drugs to prevent gastrointestinal bleeding clinical world. However, in recent years many studies have reported that the combination of PPIs with aspirin and clopidogrel can lead to an increase in cardiovascular events, but whether the increased risk of cardiovascular events and their mechanisms in clinical practice remains controversial. Purpose. To explore proton pump inhibitor (PPI) pantoprazole and esomeprazole has the dual anti-platelet drug therapy in patients with coronary heart disease antiplatelet effects of aspirin and clopidogrel. (2) to explore the liver enzyme CYP2C19 * 2 genotype antiplatelet effects of clopidogrel; while understanding the impact of prevention interventions in the treatment of different CYP2C19 genotype on PPI. Observed pantoprazole the azole, esomeprazole before and after the intervention of coronary heart disease in patients with gastrointestinal symptoms, cardiovascular adverse events in order to identify both PPI protective effect on the gastric mucosa and whether clopidogrel influential anti-platelet effect. The method 340 need to receive aspirin and clopidogrel dual antiplatelet therapy and in the interests of the gastrointestinal damage low risk of coronary heart disease patients included in the study. All patients were randomly divided into three groups, in which the control group of 142 people, that is, on the basis of the original medication, do not accept any stomach treatment; the pantoprazole group of 86 people, that is, on the basis of the original medication, accept the Pan care omeprazole (40 mg qd) in the treatment of 6 months; the esomeprazole group of 112 people, that is, on the basis of the original medication, receiving esomeprazole (20 mg qd) treatment for 6 months. Specimens from patients with blood detection of hepatic drug metabolizing enzyme CYP2C19 * 2 genotype, P-selectin, maximum platelet aggregation rate, 5 minutes platelet aggregation values, while specimens from stool specimens was measured fecal occult blood; intervention intervention in June after treatment specimens from patients with venous line P-selectin, maximum platelet aggregation rate, 5 minutes platelet aggregation value detection. The whole process of intervention, close follow-up and record the patient's cardiovascular adverse events (cardiac death, myocardial ischemia, myocardial infarction, chest pain admission), gastrointestinal symptoms (abdominal pain, bloating, acid reflux, heartburn, abdominal discomfort, diarrhea, nausea, vomiting) and gastrointestinal bleeding were observed. Results of 340 cases of patients enrolled, a total of 316 people completed the follow-up study, 24 patients were lost; blank patients 142 out of 133 completed follow-up, nine were lost to follow-dropout rate of 6.34%; the esomeprazole group of 112 103 people completed the follow-up, nine were lost to follow-dropout rate 8.04%; the pantoprazole group of 86 people 80 people completed follow-up, lost six, lost 6.98%. Lost to follow The main reason for the withdrawal itself, dressing or unable to return to hospital for examination, the overall dropout rate of 7.06%. The general situation of the three groups of patients, including age, sex, liver and kidney function, heart and lung function, comorbidities and medications were no significant differences, comparable. (1) maximum platelet aggregation rate: intervention to the control group before treatment was 36.09 ± 0.84% ??after the intervention to 37.73 ± 24.05; the esomeprazole group before and after the intervention were 35.54 ± 0.97% and 40.40 ± 20.51%; pantoprazole the azole group before and after the intervention were 35.29 ± 1.16% and 39.85 ± 16.82%. Although the two PPI treatment compared with the previous maximum platelet aggregation rate tended to increase, but the maximum platelet aggregation rate in the three groups of patients before and after treatment there was no significant difference (P gt; 0.05). (2) 5 minutes maximum aggregation rate: before and after the intervention of the control group were 30.61 ± 5.33% and 33.48 ± 2.23% before the intervention of the pantoprazole group was 31.28 ± 8.64%, 35.98 ± 7.38% after the intervention, esomeprazole The azole group before and after the intervention were 32.07 ± 4.21% and 36.20 ± 2.23%, the three groups of patients before and after the intervention, the difference was not significant (P GT; 0.05),. (3) p-selectin: control group intervention before p-selectin levels (66.30 ± 9.50) ng / ml, the pantoprazole group intervention before p-selectin levels (62.3 ± 16.99) ng / L, Esso omeprazole group before the intervention (66.57 ± 18.62) ng / L, intervention p-selectin was no difference between the groups before treatment; p-selectin levels in the control group after the intervention was 63.06 ± 14.38) ng / ml; pantoprazole group p-selectin levels after the intervention (84.62 ± 31.02) ng / L; esomeprazole group after the intervention (77.47 ± 35.74) ng / L; intervention than the control treatment the Hou Aisuo esomeprazole group and pantoprazole group p-selectin levels were significantly increased (P lt; 0.001), but no difference (P gt; 0.05) p-selectin levels in the the esomeprazole group with the pantoprazole group. Meaningful difference in the esomeprazole group and pantoprazole group before and after the intervention (P lt; 0.05) (4) hepatic drug metabolizing enzyme CYP2C19 * 2 genotype distribution: all 316 patients completed follow-up genotype for the wild-type, 105 (33.2%), heterozygous 165 (52.2%), The mutant homozygous 46 (14.6%); the blank group wild-type, heterozygous and homozygous type were 38 (28.6%), 74 (55.6%) and 21 (15.8%); Pan Pantoprazole group of wild-type, heterozygous and homozygous mutation in 30 (37.5%), 40 (50.0%), 10 (12.5%), the esomeprazole group of wild type, mutant heterozygotes and mutation homozygous were 37 (35.9%), 51 (49.5%), 15 (14.6%); each intervention group genotype distribution was no significant difference (P gt; 0.05) (5) hepatic drug metabolizing enzyme CYP2C19 * 2 genotype for each intervention group platelet aggregation: In the control group, in the wild-type, heterozygous and mutant homozygous group before and after the intervention maximum platelet aggregation rate and 5 minutes platelet aggregation rate was no significant difference (P gt; 0.05) In the pantoprazole group, the maximum platelet aggregation rate in the wild type before and after the intervention and five minutes aggregation rate (before intervention: 37.08 ± 12.74%; 33.93 ± 13.94%), and (after the intervention: 39.67 ± 16.68; 32.3 ± 18.86 %), heterozygous zygote before and after the intervention of maximum platelet aggregation rate and five-minute aggregation rate (before intervention: 35.69 ± 13.23%; 36.79 ± 12.65%), and (after the intervention: 38.70 ± 17.17%; 35.63 ± 18.67%) homozygote before and after the intervention, maximum platelet aggregation rate and the five-minute aggregation (before intervention: 38.81 ± 14.23%; 37.61 ± 15.33%), and (after the intervention: 42.00 ± 16.53%; 41.3 ± 17.46%), before and after intervention maximum platelet aggregation rate of the genotype and five minutes platelet aggregation rate did not change significantly, P gt; 0.05; intervention mutant homozygous 5-minute aggregation rate than the wild-type was significantly higher, the difference was significant, P lt; 0.05. In the esomeprazole group, maximum platelet aggregation rate in the wild type before and after the intervention and five minutes aggregation rate (before intervention: 40.44 ± 14.49%; 37.62 ± 17.43%) and (after the intervention: 41.32 ± 18.67%; 34.62 ± 13.43%), maximum platelet aggregation rate in the the heterozygous intervention before and after treatment and five minutes aggregation rate (before intervention: 41.45 ± 16.73%; 38.76 ± 15.13%) and (intervention: 37.45 ± 16.73%; 37.56 ± 19.15%), wild-type and mutant heterozygous platelet aggregation indicators before and after treatment were not changed significantly, P gt; 0.05; the mutation homozygous before and after the intervention of maximum platelet aggregation rate and the five-minute aggregation rate (before intervention: 40.63 ± 10.83%; 39.87 ± 14.56%), and (after the intervention: 54.6 ± 15.84%; 42.87 ± 16.57%) after the intervention compared with the previous maximum platelet aggregation rate was significantly higher, P lt; 0.05; mutant homozygous and after the intervention maximum platelet aggregation rate and the five-minute aggregation rate than the wild-type increases, the difference was statistically significant, P lt; 0.05. (6) gastrointestinal symptoms and adverse events: 1 month follow-up control group gastrointestinal symptoms (abdominal pain, bloating, acid reflux, heartburn, abdominal discomfort, diarrhea, nausea, vomiting) 29, an incidence of 21.8% pantoprazole group (n = 8), was 10.0%, the esomeprazole group 6, the rate was 5.82%, compared with the control group, the two PPI group of gastrointestinal symptoms were significantly reduced, (P lt; 0.05). Gastrointestinal symptoms occurred 6 months follow-up, control group 19 people, the incidence of 14.28%, the esomeprazole group 5, the rate was 4.85%, the pantoprazole group 3, the rate was 2.50%, with the blank group, two gastrointestinal symptoms in the PPI group the incidence rate significantly reduced (P lt; 0.05), said the Ming Aisuo esomeprazole, pantoprazole significantly decreased the mean taking anti-platelet drugs in patients with gastrointestinal symptoms incidence, also found that taking dual antiplatelet drugs early, patients with gastrointestinal symptoms occur relatively large. (7) adverse cardiovascular events: follow-up in January found that the control group of major cardiovascular events (MACE, including cardiac death, myocardial ischemia, myocardial infarction, chest pain admission) occurred seven people, the rate was 5.26%; the pantoprazole group 5, the occurrence rate of 6.25%; esomeprazole group 6, the incidence rate of 5.82%; three groups with no difference, P GT; 0.05 mutation of the control group in all MACE 2 homozygous wild-type, heterozygous, pantoprazole 2 mutant homozygous, heterozygous, wild-type 1, esomeprazole group 3 mutations 2-type homozygous and heterozygous metabolizers; found in the follow-up of 6 months after the intervention, the control group 1, myocardial infarction, target vessel revascularization (TVR cardiac death ) 1, chest pain readmitted 5, adverse cardiovascular events of 9 people, the incidence of 6.76%; pantoprazole group 1 cardiac death, myocardial infarction people, TVR 1, chest pain again the admission adverse cardiovascular events occurred in 5 people, the incidence of 6.25%; the esomeprazole group 2 cardiac death, myocardial infarction, TVR 1, chest pain readmitted 4, the heart vascular adverse events of 9 people than 8.74%; occurrence of the esomeprazole group of MACE in the follow-up in June slightly higher compared with the pantoprazole group and the control group, but the difference was not statistically significant, P gt; 0.05 , control group homozygote wild-type, heterozygous, pantoprazole 2 mutant homozygous, heterozygous, wild-type 1, esomeprazole group 4 mutant homozygous, heterozygous, wild-type 2. Mutant homozygous for the incidence of MACE compared with wild-type multi-esomeprazole group, but the difference was not statistically significant. Conclusion: (1) PPI pantoprazole and esomeprazole effective in preventing aspirin and clopidogrel dual antiplatelet therapy caused incidence of gastrointestinal symptoms. (2) of clopidogrel and aspirin's anti-platelet effect with genotype and PPI medication, the combined use of PPIs in patients with homozygous mutant double-antibody inhibition of platelet aggregation was significantly lower than heterozygous and wild-type patients particularly evident in combination with esomeprazole (3) The combination of the PPI pantoprazole and esomeprazole can prevent dual antiplatelet therapy in patients with coronary heart disease gastrointestinal injury, but may result in such patients increase in adverse cardiovascular events.
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