Effect Of Different Proton Pump Inhibitors Or H2Receptor Antagonists On The Anti-platelet Functions Of Clopidogrel In Patients After PCI

Background and PurposeIn recent years, morbidity of the Coronary Heart Disease(CHD) has an obviousuptrend in China，especially acute coronary syndrome (acute coronary syndromeACS),with the highest mortality, impacts on the quality of life and seriouslyendangers the health of human. Therefore, the precaution and treatment of CHD arebecoming more and more important. Activation and aggregation function of plateletstart action during ACS thrombosis, so the early anti-platelet therapy can significantlyreduce the risk of morbidity and mortality of ACS, percutaneous coronary arteryinterventional therapy (percutaneous coronary intervention, PCI) has become themajor medical strategy, the guidelines recommend after and before PCI dualanti-platelet therapy should be used to prevent thrombosis[1]. With the anti-plateletdrugs applied, gastrointestinal bleeding prevalence increases markedly. Studies haveshown that the combination of proton pump inhibitors (proton pump inhibitors, PPI)or H2RA (H2receptor antagonists), and dual anti-platelet could significantly reducethe risk of upper gastrointestinal hemorrhage[2,3]. As the drug of choice for treatment and prevention of gastric and duodenal injury, PPI is widely used in the clinic[4].Previously several studies found that PPI or even H2RA (H2receptor antagonists)may reduce anti-platelet function of clopidogrel, increase in adverse cardiovascularevents and mortality rates], But recently it has also been reported PPI does not have aneffect on the anti-platelet functions of clopidogrel, which is still controversial[5-9], anddraw more attention by the cardiovascular physicians.In this study, a randomized, control study was designed to study the influence ofdifferent proton pump inhibitors or H2receptor antagonists on the anti-plateletfunctions of clopidogrel in patients with ACS24hours after PCI, which can providemore data for clinical use of rational drugs of dual anti-platelet therapy combined withPPI or H2RA in patients with coronary artery disease.MethodsThe first part of this study: Observing3days, effect of different PPI or H2RA onanti-platelet function of clopidogrel after PCISome patients who were hospitalized in our hospital of Cardiology from March toNovember in2011were selected, who met the diagnostic criteria for acute coronarysyndrome in cardiovascular treatment guidelines and recommendations, and clinicalmanifestations were unstable angina pectoris, non ST-segment elevation myocardialinfarction and ST-segment elevation myocardial infarction. Coronary heart diseasewas confirmed by coronary angiography and PCI was successful. Exclusion criteria:patients with high risk of hemorrhage, Anti-platelet and anticoagulant therapycontraindications, taking PPI or H2RA in one month, the GP II b/III a receptorantagonist was used before hospitalizing, platelet count <100g/L, Creatinineclearance <250ml/min, liver disease, gastrointestinal ulcer, New York HeartAssociation classification of heart function Ⅳ, pregnancy, suffering from cerebralvascular accident in1year. Hospitalized patients received dual anti-platelet treatmentincluding300mg/d aspirin and300-600mg/d clopidogrel as loading dose followed by75mg/d maintenance dose. After PCI for24hours, under the circumstances thatpatients were informed and consented, they were numbered according to hospitalization time, the random number table was referred to, and then the sort ofrandom numbers were carried out, subjects were randomly divided into3groups (1:1).They were given the following drugs: group A, called group PPI: group A1:esomeprazole (40mg/d,); group A2: Rabeprazole (20mg/d,); group B, named groupH2RA, group B1: ranitidine (300mg/d); group B2: famotidine (40mg/d,); group C:control group(non-drugs above). Twenty four hours after PCI (before taking PPI orH2RA) and72h after treatment, the patients with empty stomachs in each group werecollected venous blood2ml in the early morning in their elbows to inject into thevacuum test-tube of the containing0.05mol/LEDTA-Na2anticoagulants of the plastic,3000r/min centrifuge15min immediately to collect the upper fluid (plasma, yellow),Surfactant protein markers:plasma CD62P and GPIIb/IIIa were measured by ELISAmethod and all patients were fasting blood2ml to inject into vacuum anticoagulanttest tube containing38g/L sodium citrate (9:1), and platelet aggregation function(PAgT,ADP) was measured by impedance detection method in2h calculated aboutthe changes.Second part of this study: One month follow up of the study on theinteractionbetween different PPI or H2RA and Clopidogrel in Patients after PCI infollow-up period: patients with ACS who had received PCI were given aspirin300mg/d,75mg/d maintenance dose for anti-platelet therapy after discharge fromhospital according to the selection criteria, and all patients continued to take thefollowing drugs: group A (group PPI,): group A1: PPI drugs esomeprazole (40mg/d,);group A2: PPI drugs Rabeprazole (20mg/d,); group B (group H2RA,): group B1:H2RA drug ranitidine (300mg/d,); group B2: H2RA drugs famotidine (40mg/d,);group C: control group (non-drugs above);24h after PCI (before taking PPI or H2RA)and one month after treatment, all patients in each group were fasting blood, andSurfactant protein markers: Plasma CD62P and GPIIb/IIIa were measured by ELISAmethod and platelet aggregation function (PAgT,ADP) was measured by impedancedetection method and calculated about the changes.Results The first part: A total of150hospitalized patients with ACS treated by PCI wereinvolved in the study according to inclusion criteria, then the patients were randomlydivided into3groups: group A (sixty cases of patients), called group PPI: group A1:esomeprazole (n=30); group A2: Rabeprazole (n=30); group B (sixty cases ofpatients), named group H2RA, group B1: ranitidine (n=30); group B2: famotidine (n=30); group C: control group (non-drugs above, n=30). There was no bias aboutbaseline data by balanced test1. the comparison among group PPI,H2RA and groupcontrol No visible statistical significance was found in P-selection (CD62P), plateletgranule membrane glycoprotein△b/△a （GP△b/△a）and Platelet aggregationfunction (PAgT) among three groups24h (before PPI or H2RA treatment) after PCIamong group A,B and C (P>0.05); There was also no statistic difference about△C D62P,△GP△b/△a and△PAgT after treatment72h after PCI（P＞0.05）. Therewas still no statistic significance about△CD62P,△G P△b/△a and△PAgT beforeand after treatment between group A and B（P＞0.05）.2. The comparison betweendifferent PPI or H2RA and group control The difference was not significant aboutCD62P，GPⅡb/Ⅲa and PAgT in group comparison24h (before PPI or H2RAtreatment) after PCI within group A1，A2as well as B1,B2and C(P>0.05); There wasalso no statistical significance about△CD62P,△GP Ⅱb/Ⅲa and△PAgT in groupcomparison72h after PCI in group A1and A2, B1and B2and C(P>0.05). Thedifference was still no statistical significance about△CD62P,△GP Ⅱb/Ⅲa and△PAgT before and after treatment in group comparison between group A1and A2andbetween B1and B2(P>0.05).The second part:150selected patients were followed up for a month,18patientswere stopped test due to poor compliance or losing follow-up. The remaining patientswere132: group A (group PPI,54cases of patients): group A1: PPI drugsesomeprazole (n=28); group A2: PPI drugs Rabeprazole (n=26); group B (group H2RA,49cases of patients): group B1: H2RA drug ranitidine (n=25); group B2:H2RA drugs famotidine (n=24); group C: control group (n=29)1. Compare group PPI,H2RA and group control There was no statistical significance about P-selectin(CD62P), platelet granule membrane glycoprotein Ⅱb/Ⅲa（GP Ⅱb/Ⅲa）and Plateletaggregation function (PAgT) in group comparison24h (before PPI or H2RA treatment)after PCI in group A,B and C(P>0.05); There was also no statistical significanceabout△CD62P,△GP Ⅱb/Ⅲa and△PAgT after treatment a month after PCI（P＞0.05）; There was still no statistic significance about△CD62P,△GPⅡb/Ⅲa and△PAgT before and after treatment between group A and B（P＞0.05）2. Comparedifferent types of PPI or H2RA with group C There was no statistical significanceabout CD62P,GPⅡb/Ⅲa and PAgT in group comparison24h (before PPI or H2RAtreatment) after PCI in group A1,A2,B1,B2and C(P>0.05); The difference was alsono statistical significant about△CD62P,△GPⅡb/Ⅲa and△PAgT a month afterPCI in group A1and A2,B1and B2and C(P>0.05). The difference was still nostatistical significance about△CD62P,△GP Ⅱb/Ⅲa and△PAgT before and aftertreatment in group comparison between group A1and A2and between B1and B2(P>0.05). The difference was still no statistical significance about△CD62P,△GPⅡb/Ⅲa and△PAgT before and after treatment in group comparison between groupA1and A2and between B1and B2(P>0.05).Conclusions1. The combination of different PPI or H2RA and clopidogrel can not reduceanti-platelet function of clopidogrel in a short period.2. After different PPI or H2RA and clopidogrel are combined for a month, theinteractions between the applications of drugs are not obvious, and maybe theirclinical combination is reasonable and safe.