Analysis of the Therapeutic Effect of Clopidogrel Bisulfate Tablets + Aspirin Enteric-Coated Tablets on Acute Myocardial Infarction

Objective:To investigate and analyze the clinical effect of clopidogrel bisulfate tablets combined with aspirin enteric-coated tablets on acute myocardial infarction(AMI)patients.Methods:The study period was from January 2020 to December 2023,the sample source was 82 AMI patients admitted to our hospital,grouped into an observation group(n=41)and a control group(n=41)by the numerical table method.The patients in the control group were treated with aspirin enteric-coated tablets,and the patients in the observation group were treated with aspirin enteric-coated tablets combined with clopidogrel bisulfate.The clinical efficacy,coagulation indexes,and the incidence of cardiovascular adverse events between the two groups were compared.Results:The clinical efficacy of the observation group was higher than that of the control group(P<0.05);the platelet aggregation rate(PAR)of the observation group was lower than that of the con-trol group after treatment(P<0.05),and there was no significant difference in the prothrombin time(PT)and activated partial thromboplastin time(APTT)between the two groups(P>0.05).The incidence of cardiovascular adverse events in the observation group was lower than that of the control group(P<0.05).Conclusion:The treatment effect of clopidogrel bisulfate tablets combined with aspirin enteric-coated tablets on AMI patients is remarkable.It reduces the PAR and the incidence of cardiovascular adverse events,so this treatment method should be popularized.

Analysis of the Effectiveness of Clopidogrel Combined with Aspirin in the Treatment of Coronary Heart Disease in Community-Dwelling Elderly

Objective:To analyze the combined therapeutic effect of clopidogrel(CLO)and aspirin(ASP)on coronary heart disease(CHD)in community-dwelling elderly.Methods:Thirty elderly patients with CHD who were admitted to the Xinxin Community Health Service Station,Pangzhuang Street,Quanshan District,Xuzhou City,from November 2020 to November 2022 were selected and randomly grouped into an observation group and a control group,with 15 cases in each group.The observation group was given the combination of CLO and ASP and the reference group was given only ASP.The total effective rate and other treatment indicators between the two groups were compared.Results:The total effective rate of the observation group(93.33%)was higher than that of the reference group(60.00%)(P<0.05).The adverse drug reaction rate(13.33%)and long-term cardiovascular adverse event rate(6.67%)of the observation group were lower than those of the reference group at 46.67%and 40.00%respectively,(P<0.05).Before treatment,the two groups had no difference in the quality-of-life scores(P>0.05).After treatment,the quality-of-life scores of the observation group were higher than those of the reference group(P<0.05).Conclusion:CLO combined with ASP improved the therapeutic effect of community-dwelling elderly patients with CHD,reduced adverse reactions during medication,prevented adverse cardiovascular events,and comprehensively improved the patient’s quality of life.

An Observational Study of the Relationship Between Outcome and Platelet Reactivity in Chinese Patients Undergoing PCI Loading with 600 mg Clopidogrel

Objectives:We sought to determine whether high posttreatment platelet reactivity(HPPR)to a 600 mg loading dose of clopidogrel affects outcomes in Chinese patients with acute coronary syndrome(ACS)following percutaneous coronary intervention(PCI)and to investigate whether there is a relationship between the number of platelet reactivity units(PRUs)and the characteristics of the patients.Background:Although impaired platelet response to clopidogrel is a strong predictor of unfavorable outcome after PCI,the impact of HPPR to a 600 mg loading dose of clopidogrel in Chinese patients with ACS undergoing PCI is still unknown.Methods:We performed observational research on 134 unselected patients with ACS undergoing urgent or planned PCI with a 600 mg loading dose of clopidogrel.Platelet activation was expressed as the PRU value measured by the VerifyNow assay.Results:Among the 134 patients(mean age 60.62 years[standard deviation 9.13 years],60.4%male),there were 46 patients with HPPR(34.3%)and 88 patients without HPPR(65.7%).At a mean follow-up of 6 months(standard deviation 1 month),the rates of cardiac death,unstable angina,and rehospitalization for target lesion revascularization were higher in the HPPR group(19.6%vs.6.8%,P=0.029).Multivariate analysis identifi ed hemoglobin level and sex as independent predictors of the PRU value(y=456.355−1.736 x 1−31.880 x 2,P<0.05).On receiver operating characteristic curve analysis,PRU values could signifi cantly discriminate between patients with and patients without cardiac death,unstable angina,and rehospitalization for target lesion revascularization(area under the curve 0.758,95%confi dence interval 0.62–0.85,P=0.001,P<0.05).Conclusion:In patients with ACS,HPPR to a 600 mg loading dose of clopidogrel is associated with worse outcomes after PCI.There is some relationship between the PRU value and the hemoglobin level and sex.PRU values can predict the prognosis.

Clinical importance of aspirin and clopidogrel resistance

Aspirin and clopidogrel are important components of medical therapy for patients with acute coronary syndromes, for those who received coronary artery stents and in the secondary prevention of ischaemic stroke. Despite their use, a significant number of patients experience recurrent adverse ischaemic events. Interindividual variability of platelet aggregation in response to these antiplatelet agents may be an explanation for some of these recurrent events, and small trials have linked "aspirin and/or clopidogrel resistance", as measured by platelet function tests, to adverse events. We systematically reviewed all available evidence on the prevalence of aspirin/clopidogrel resistance, their possible risk factors and their association with clinical outcomes. We also identified articles showing possible treatments. After analyzing the data on different laboratory methods, we found that aspirin/clopidogrel resistance seems to be associated with poor clinical outcomes and there is currently no standardized or widely accepted definition of clopidogrel resistance. Therefore, we conclude that specific treatment recommendations are not established for patients who exhibit high platelet reactivity during aspirin/clopidogrel therapy or who have poor platelet inhibition by clopidogrel.

Profound thrombocytopenia induced by clopidogrel with a prior history of long-term safe administration

Clopidogrel has shown an excellent safety,tolerability and efficacy ever since its marketing.However,here we report a rare case with profound thrombocytopenia following clopidogrel administration previously safely exposed to this same drug.This reminds us that thrombocytopenia might be induced by clopidogrel even with a prior,safe history of long-term administration.

Clopidogrel resistance response in patients with coronary artery disease and metabolic syndrome： the role of hyperglycemia and obesity

Background Despite the proven benefits of clopidogrel combined aspirin therapy for coronary artery disease （CAD）, CAD patients with metabolic syndrome （MS） still tend to have coronary thrombotic events. We aimed to investigate the influence of metabolic risk factors on the efficacy of clopidogrel treatment in patients with CAD undergoing percutaneous coronary intervention （PCI）. Methods Cohorts of 168 MS and 168 non-MS subjects with CAD identified by coronary angiography （CAG） were enrolled in our study. MS was defined by modified Adult Treatment Panel Ⅲ criteria. All subjects had taken 100 mg aspirin and 75 mg clopidogrel daily for more than 1 month, and administered loading doses of 600 mg clopidogrel and 300 mg aspirin before PCI. Blood samples were taken 24 h after the loading doses of clopidogrel and aspirin. Platelet aggregation was measured using light transmittance aggregometry （LTA） and thrombelastography （TEG）. Clopidogrel resistance was defined as more than 50% adenosine diphosphate （ADP） induced platelet aggregation as measured by TEG. Re- sults Platelet aggregation inhibition rate by ADP was significantly lower in patients with MS as measured both by TEG （55% ＋ 31% vs. 68% ± 32%; P 〈 0.001） and LTA （29% ± 23% vs. 42% ± 29%; P 〈 0.001）. In the multivariate analysis, elderly [OR （95% CI）： 1.483 （1.047±.248）; P = 0.002], obesity [OR （95% CI）： 3.608 （1.241-10.488）; P = 0.018], high fasting plasma glucose level [OR （95% CI）： 2.717 （1.176±.277）; P = 0.019] and hyperuricemia [OR （95% CI）： 2.583 （1.095-6.094）; P = 0.030] were all statistically risk factors for clopido- grel resistance. CAD patients with diabetes and obesity were more likely to have clopidogrel resistance than the CAD patients without dia- betes and obesity [75% （61/81） vs. 43% （67/156）; P 〈 0.001]. Conclusions CAD patients with MS appeared to have poorer antiplatelet response to clopidogrel compared to those without MS. Obesity, diabetes and hyperuricemia were all significantly associated with clopido- grel resistance.

Impact of concomitant use of proton pump inhibitors and clopidogrel or ticagrelor on clinical outcomes in patients with acute coronary syndrome

Background There is great debate on the possible adverse interaction between proton pump inhibitors （PPIs） and clopidogrel. In ad- dition, whether the use of PPIs affects the clinical efficacy of ticagrelor remains less known. We aimed to determine the impact of concomi- tant administration of PPIs and clopidogrel or ticagrelor on clinical outcomes in patients with acute coronary syndrome （ACS） after percuta- neous coronary intervention （PCI）. Methods We retrospectively analyzed data fi＇om a ＂real world＂, international, multi-center registry between 2003 and 2014 （n = 15,401） and assessed the impact of concomitant administration of PPIs and clopidogrel or ticagrelor on 1-year composite primary endpoint （all-cause death, re-infarction, or severe bleeding） in patients with ACS after PCI. Results Of 9429 patients in the final cohort, 54.8% （n = 5165） was prescribed a PPI at discharge. Patients receiving a PPI were older, more often female, and were more likely to have comorbidities. No association was observed between PPI use and the primary endpoint for patients receiving clopidogrel （ad- justed HR： 1.036; 95% CI： 0.903-1.189） or ticagrelor （adjusted HR： 2.320; 95% CI： 0.875-45.151） （Pinteraction = 0.2004）. Similarly, use of a PPI was not associated with increased risk of all-cause death, re-infarction, or a decreased risk of severe bleeding for patients treated with either clopidogrel or ticagrelor. Conclusions In patients with ACS following PCI, concomitant use of PPIs was not associated with in- creased risk of adverse outcomes in patients receiving either clopidogrel or ticagrelor. Our findings indicate it is reasonable to use a PPI in combination with clopidogrel or ticagrelor, especially in patients with a higher risk of gastrointestinal bleeding.

Comparison of Treatment Outcomes of Ticagrelor and Clopidogrel among Patients Undergoing Percutaneous Coronary Intervention: A Meta-analysis

We performed a meta-analysis of randomized controlled trials（RCTs） to investigate the efficacy and safety of ticagrelor（TIC） vs. clopidogrel（CLO） in patients undergoing percutaneous coronary intervention（PCI）. In Jun 2016, a literature search was started and all the studies were conducted from 2010 to 2015. We systematically searched the literature through the MEDLINE database, Cochrane library, and EMBASE database. Quality assessments were evaluated with Jadad quality scale. Data were extracted considering the characteristics of efficacy and safety designs. Six RCTs enrolling 26 244 participants and satisfying the inclusion criteria were finally analyzed. There was a significant decrease of all-cause mortality（MD=0.83, 95%CI=0.74–0.93, P=0.001） and myocardial infarction（MI）（MD=0.78, 95%CI=0.70–0.88, P=0.000）. There were no significant differences in stroke（MD=1.34, 95%CI=0.99–1.79, P=0.06）, total bleeding（MD=0.97, 95%CI=0.84–1.12, P=0.66）, minor or major bleeding（MD=1.06, 95%CI=0.94–1.19, P=0.35） in patients undergoing PCI after treatment with TIC vs. CLO. TIC could be more significant in decreasing all-cause mortality and MI than CLO, but there were no significant differences between TIC and CLO in inhibiting stroke, major bleeding, major or minor bleeding in patients undergoing PCI.

Clinical evidence of interaction between clopidogrel and proton pump inhibitors

Clopidogrel is approved for reduction of atherothrombotic events in patients with cardiovascular(CV)and cerebrovascular disease.Dual antiplatelet therapy with aspirin and clopidogrel decreases the risk of major adverse cardiac events after acute coronary syndrome or percutaneous coronary intervention,compared with aspirin alone.Due to concern about gastrointestinal bleeding in patients who are receiving clopidogrel and aspirin therapy,current guidelines recommend combined use of a proton pump inhibitor(PPI)to decrease the risk of bleeding.Data from previous pharmacological studies have shown that PPIs,which are extensively metabolized by the cytochrome system,may decrease the ADP-induced platelet aggregation of clopidogrel. Results from retrospective cohort studies have shown a higher incidence of major CV events in patients re-ceiving both clopidogrel and PPIs than in those without PPIs.However,other retrospective analyses of randomized clinical trials have not shown that the concomitant PPI administration is associated with increased CV events among clopidogrel users.These controversial results suggest that large specific studies are needed. This article reviews the metabolism of clopidogrel and PPIs,existing clinical data regarding the interaction between clopidogrel and PPIs,and tries to provide recommendations for health care professionals.

Clopidogrel improves aspirin response after off-pump coronary artery bypass surgery

We sought to assess the incidence of aspirin resistance after off-pump coronary artery bypass （OPCAB） surgery, and investigate whether clopidogrel can improve aspirin response and be safely applied early after OPCAB surgery. Sixty patients who underwent standard OPCAB surgery were randomized into two groups. One group （30 patients） received mono-antiplatelet treatment （MAPT） with aspirin 100 mg daily and the other group received dual anfiplatelet treatment （DAPT） with aspirin 100 mg daily plus clopidogrel 75 mg daily. Platelet aggregations in response to arachi- donic acid （PLAA） and adenosine diphosphate （ADP） （PLADP） were measured preoperatively and on days 1 to 6, 8 and 10 after the antiplatelet agents were administered. A PLAA level above 20% was defined as aspirin resistance. Postoperative bleeding and other perioperative variables were also recorded. There were no significant differences between the two groups in baseline characteristics, average number of distal anastomosis, operation time, postoperative bleeding, ventilation time and postoperative hospital stay. However, the incidence of aspirin resistance was significantly lower in the DAPT group than that in the MAPT group on the first and second day after antiplatelet agents were given （62.1% vs, 32.1%, 34.5% vs. 10.7%, respectively, both P 〈 0.05）. There was no significant difference in postoperative complication between the two groups. DAPT with aspirin and clopidogrel can be safely applied to OPCAB patients early after the procedure. Moreover, clopidogrel reduces the incidence of OPCAB-related aspirin resistance.

Variability of platelet aggregation in patients with clopidogrel treatment and hip fracture: A retrospective case-control study on 112 patients

AIM: To identify the rate of non-responders to clopidogrel treatment in hip fracture patients and study how non-responders differ from controls.METHODS: In a retrospective case-control study we included 28 cases of acute proximal femoral fracture with clopidogrel treatment 2011 to 2013. Eighty-four controls from the same time period were included. Data collected included response to clopidogrel measured with multiple electrode aggregometry(MEA), intraoperative bleeding, erythrocyte transfusion, time to surgery and the incidence of adverse events up to 3 mo after surgery. RESULTS: Eight(29%) of the 28 cases were nonresponders. The median intraoperative bleeding was 300 mL(range, 0-1500), and was lower for non-responders(50 m L) but did not reach statistical significance. Erythrocyte transfusions did not differ between responders, non-responders and controls. Forty-five(40%) of 112 patients had adverse events postoperatively but the rate did not differ between patients with and without clopidogrel treatment.CONCLUSION: Almost one-third of patients withclopidogrel treatment and an acute proximal femoral fracture are non-responders to antiplatelet therapy and can be operated without delay.

Clinical relevance of clopidogrel-proton pump inhibitors interaction

Clopidogrel is a widely used antiplatelet agent for the secondary prevention of cardiovascular events in patients with stable coronary heart disease, acute coronary syndromes and ischemic stroke. Even though clopidogrel is safer than aspirin in terms of risk for gastrointestinal(GI) bleeding, the elderly, and patients with a history of prior GI bleeding, with Helicobacter pylori infection or those who are also treated with aspirin, anticoagulants, corticosteroids or nonsteroidal antiinflammatory drugs are at high risk for GI complications when treated with clopidogrel. Accordingly, proton pump inhibitors are frequently administered in combination with clopidogrel to reduce the risk for GI bleeding. Nevertheless, pharmacodynamic studies suggest that omeprazole might attenuate the antiplatelet effect of clopidogrel. However, in observational studies, this interaction does not appear to translate into increased cardiovascular risk in patients treated with this combination. Moreover, in the only randomized, double-blind study that assessed the cardiovascular implications of combining clopidogrel and omeprazole, patients treated with clopidogrel/omeprazole combination had reduced risk for GI events and similar risk for cardiovascular events than patients treated with clopidogrel and placebo. However, the premature interruption of the study and the lack of power analysis in terms of the cardiovascular endpoint do not allow definite conclusions regarding the cardiovascular safety of clopidogrel/omeprazole combination. Other proton pump inhibitors do not appear to interact with clopidogrel. Nevertheless, given the limitations of existing observational and interventional studies, the decision to administer proton pump inhibitors to patients treated with clopidogrel should be individualized based on the patient's bleeding and cardiovascular risk.

Bleeding risk with clopidogrel and percutaneous endoscopic gastrostomy

AIM To compare bleeding within 48 h in patients undergoing percutaneous endoscopic gastrostomy(PEG) with or without clopidogrel.METHODS After institutional review board approval, a retrospective study involving a single center was conducted on adult patients having PEG(1/08-1/14). Patients were divided into two groups: Clopidogrel group consisting of those patients taking clopidogrel within 5 d of PEG and the non-clopidogrel group including those patients not taking clopidogrel within 5 d of the PEG.RESULTS Three hundred and nineteen PEG patients were found. One hundred and sixty-eight males and 151 females with mean body mass index 28.47 ± 9.75 kg/m2 and mean age 65.03 ± 16.11 years were identified. Thirtythree patients were on clopidogrel prior to PEG with 286 patients not on clopidogrel. No patients in either group developed hematochezia, melena, or hematemesiswithin 48 h of percutaneous endoscopic gastrostomy(PEG). No statistical differences were observed between the two groups with 48 h for hemoglobin decrease of > 2 g/dL(2 vs 5 patients; P = 0.16), blood transfusions(2 vs 7 patients; P = 0.24), and repeat endoscopy for possible gastrointestinal bleeding(no patients in either group). CONCLUSION Based on the results, no significant post-procedure bleeding was observed in patients undergoing PEG with recent use of clopidogrel.

Effects of omeprazole or pantoprazole on platelet function in non-ST-segment elevation acute coronary syndrome patients receiving clopidogrel

Background: This study evaluated the effect of omeprazole or pantoprazole on platelet reactivity in non-STsegment elevation acute coronary syndrome(NSTE-ACS) patients receiving clopidogrel.Methods: Consecutive patients with NSTE-ACS(n =620) from general hospital of Shenyang Military Command were randomized to the omeprazole or pantoprazole(20mg/d) group(1:1), and received routine dual antiplatelet treatment. Patients' reversion rate of adenosine diphosphate-induced platelet aggregation(ADP-PA) was assessed at baseline, 12 to 24 h after administration of medication, and after 72 h of percutaneous coronary intervention(PCI). The primary endpoint of the study was platelet reactivity assessed with ADP-PA at 30 days after PCI. Adverse events(AEs) were recorded for 30-day and 180-day follow-up periods.Results: There were no significant differences between both the groups in platelet response to clopidogrel at 12–24h after drug administration(54.09%±18.90% vs. 51.62%±19.85%, P=0.12), 72 h after PCI(52.15%±19.45% vs. 49.66%±20.05%, P=0.18), and 30 days after PCI(50.44%±14.54% vs. 48.52%±15.08%, P=0.17). The rate of AEs did not differ significantly between groups during the 30-day(15.2% vs. 14.8%, P=0.91) and 180-day(16.5% vs. 14.5%, P=0.50) follow-up periods after PCI.Conclusion: The addition of omeprazole or pantoprazole to clopidogrel did not restrict the effect of platelet aggregation by reducing the conversion of clopidogrel. Compared with clopidogrel alone, pantoprazole-clopidogrel and omeprazoleclopidogrel combinations did not increase the incidence of adverse clinical events during 30-day and 180-day follow-up periods after PCI.

Separation of Enantiomers of Clopidogrel on Chiral Stationary Phases by Packed Column Supercritical Fluid Chromatography

A packed column supercritical fluid chromatography (SFC) method for the separation of clopidogrel enantiomers on a chiral stationary phase and CO2 with modifier as mobile phase has been developed at an analytical scale. Among 11 different 2 stationary phases the Chiral cel OD-H column showed by far the best separation properties. The influence of different modifiers, injection solvents, temperature, and pressure, and density of the fluid, respectively, on the separation behaviour has been studied. It was found that the separation behaviour strongly depends on the type of modifier and the modifier content. Temperature and pressure are of less influence.

The clinical application of clopidogrel in current coronary artery surgery

The article presents an overview of the current clinical application of clopidogrel in coronary artery surgery. The viewpoint is that clopidogrel can reduce preoperative and postoperative ischemic events of coronary artery bypass grafting（CABG）. With the development of standardized medication and the corresponding preventive technique, it will be of great value to reduce hemorrhage complications and obtain the maximum benefit from clopidogrel＇ s anti-platelet properties.

Determination of Clopidogrel Carboxylic Acid in Human Plasma by LC-MS/MS

Background: Clopidogrel, is a thienopyridine derivative labeled for use to prevent thrombosis after coronary artery stenting. Pharmacokinetics of clopidogrel is studied indirectly by quantification of carboxylic acid which is a major metabolite of Clopidogrel. Objective: The aim of this work is to develop and validate a rapid, simple and sensitive LC/MS/MS assay method for the determination of Clopidogrel carboxylic acid in human plasma using Clopidogrel-D4-carboxylic acid as internal standard. Methods: Analytes was extracted from 200 μl of plasma by a simple liquid-liquid extraction using diethyl ether – n-hexane (80:20, v/v). The chromatographic separations were achieved on a C18 column using Methanol, de-ionized water and formic acid as a mobile phase at flow rate of 0.5 ml/minute. Analysis was monitored by multiple reactions monitoring mode based on m/z transition of 308.10→113 for Clopidogrel carboxylic acid and 312.10→129 for internal standard. Result: The method had a total run time of about 4 minutes. The lower limit of quantification (LLOQ) was 25 ng/ml showing good linearity over the working range of 25 – 3000 ng/ml (r ≥ 0.999). The intra- and inter day accuracies were 90% - 98% and 92.138% - 96.889% respectively (deviation within acceptable range ≤ 10%).Conclusion: It was shown that this method is suitable for pharmacokinetic study following oral administration of Clopidogrel and can be successfully applied to the therapeutic drug monitoring of Clopidogrel in Clopidogrel-treated patients.

Alternatives to clopidogrel for acute coronary syndromes:Prasugrel or ticagrelor?

Clopidogrel is a mainstay in the treatment of patients with acute coronary syndromes or those receiving endovascular prostheses.However,its efficacy has been challenged in the recent past by studies suggesting variable individual responsiveness and by new,more potent competitors,such as prasugrel and ticagrelor. But what is the actual body of evidence in support of clopidogrel?Is there any dark side of the moon?What is the role of prasugrel,which has already been approved in Europe and in the United States?And what will be the future role of ticagrelor,when approved for routine clinical practice?We hereby concisely summarize the scope of this clinical choice,providing arguments in favor and against each of the three antiplatelet agents:clopidogrel,prasugrel,and ticagrelor.

Effect of clopidogrel in bone healing-experimental study in rabbits

BACKGROUND Clopidogrel is a widely prescribed drug for prevention of myocardial infarction and stroke in patients at risk.It inhibits thrombus formation via inhibition of the P2Y12 purinergic receptor on platelets,which is important in their activation by ADP.However,the P2Y12 receptor has also been found to be expressed in both osteoblasts and osteoclasts.Accumulated evidence suggests that purinergic receptors regulate important functions of bone turnover.Previous studies on the effect of clopidogrel on bone metabolism indicated potential harmful effects,but their results remain conflicting.Thus,clopidogrel treatment may affect bone healing,but it has not yet been studied.AIM To evaluate if continuous perioperative clopidogrel treatment has any negative effect on bone healing in the rabbit calvarial defect model.METHODS Sixteen male white New Zealand rabbits were randomly assigned in two groups:One group received daily 3 mg/kg of clopidogrel per os and the other group received the vehicle alone for a week prior to the surgical procedures;the treatments were continued for another 6 wk postoperatively.The surgical procedures included generation of two circular calvarial defects 11 mm in diameter in every animal.After the 6-wk period of healing,postmortem radiographic and histomorphometric evaluation of the defects was performed.RESULTS Both the surgical procedures and the postoperative period were uneventful and well tolerated by all the animals,without any surgical wound dehiscence,signs of infection or other complication.New bone was formed either inwards from the defect margins or in the central portion of the defect as separated bony islets.While defect healing was still incomplete in both groups,the clopidogrel group had significantly improved radiographic healing scores.Moreover,the histomorphometric analysis showed that bone regeneration(%)was 28.07±7.7 for the clopidogrel group and 19.47±4.9 for the control group,showing a statistically significant difference between them(P=0.018).Statistically significant difference was also found in the defect bridging(%),i.e.72.17±21.2 for the clopidogrel group and 41.17±8.5 for the control group,respectively(P=0.004),whereas there was no statistical difference in bone tissue density between the groups.CONCLUSION Our results indicate that maintenance of perioperative clopidogrel treatment does not negatively affect bone healing but rather promotes it.Further research is needed in order to find useful applications of this finding.

Clopidogrel and proton pump inhibitors-where do we stand in 2012?

Clopidogrel in association with aspirine is considered state of the art of medical treatment for acute coronary syndrome by reducing the risk of new ischemic events.Concomitant treatment with proton pump inhibitors in order to prevent gastrointestinal side effects is recommended by clinical guidelines.Clopidogrel needs metabolic activation predominantly by the hepatic cytochrome P450 isoenzyme Cytochrome 2C19(CYP2C19) and proton pump inhibitors(PPIs) are extensively metabolized by the CYP2C19 isoenzyme as well.Several pharmacodynamic studies investigating a potential clopidogrel-PPI interaction found a significant decrease of the clopidogrel platelet antiaggregation effect for omeprazole,but not for pantoprazole.Initial clinical cohort studies in 2009 reported an increased risk for adverse cardiovascular events,when under clopidogrel and PPI treatment at the same time.These observations led the United States Food and Drug Administration and the European Medecines Agency to discourage the combination of clopidogrel and PPI(especially omeprazole) in the same year.In contrast,more recent retrospective cohort studies including propensity score matching and the only existing randomized trial have not shown any difference concerning adverse cardiovascular events when concomitantly on clopidogrel and PPI or only on clopidogrel.Three meta-analyses report an inverse correlation between clopidogrel-PPI interaction and study quality,with high and moderate quality studies not reporting any association,rising concern about unmeasured confounders biasing the low quality studies.Thus,no definite evidence exists for an effect on mortality.Because PPI induced risk reduction clearly overweighs the possible adverse cardiovascular risk in patients with high risk of gastrointestinal bleeding,combination of clopidogrel with the less CYP2C19 inhibiting pantoprazole should be recommended.