Objective To systematically evaluate impact of perioperative use of clopidogrel on coronary bypass grafting (CABG) patients for anti-platelet treatment, in order to provide evidence for the rational drug use of such patients in the perioperative period. Methods PubMed, EMbase, HighWire, CENTRAL and its affiliated clinical trial registered data center, CBM and CNKI were electronically searched from 2003 to November, 2012. Randomized controlled trials (RCTs) and non-randomized clinical trials on perioperative use of clopidogrel of CABG patients were collected. References of included studies were also retrieved. Two reviewers independently screened studies according to exclusion and inclusion criteria, extracted data, and assessed the methodological quality. Then, meta-analysis was performed using RevMan 5.0 software. Results 18 studies (including 10 RCTs and 8 non-randomized clinical trials) involving 14 592 patients were included. The results of meta-analysis showed that: a) Among 10 included RCTs, preoperative use of clopidogrel for anti-platelet treatment reduced the incidence of myocardial infarction obviously, compared with the blank control group (RR=0.63, 95%CI 0.48 to 0.83, P=0.000 9), but there is no significant difference between the two groups in blood loss amount within 24 hours after operation (MD=130, 95%CI –6.21 to 266.22, P=0.06), the number of reoperation patients because of bleeding (RR=1.42, 95%CI 0.92 to 2.20, P=0.12), and risk of postoperative short-term death (RR=1.19, 95%CI 0.89 to 1.58, P=0.24); b) Among 8 non-randomized clinical trials, there was no significant difference between the two groups in reducing the incidence of myocardial infarction (RR=0.83, 95%CI 0.30 to 2.26, P=0.71), but preoperative use of clopidogrel for anti-platelet treatment significantly increased blood loss amount within 24 hours after operation (MD=82.42, 95%CI 35.18 to 129.66, P=0.000 6), the number of reoperation patients because of bleeding (RR=1.71, 95%CI 1.07 to 2.75, P=0.03), and risk of postoperative short-term death (RR=1.89, 95%CI 1.15 to 3.12, P=0.01). Conclusion Current evidence shows that, perioperative use of clopidogrel can reduce the incidence of myocardial infarction, but doctors should consider cautiously the increased risk of bleeding, re-operation and postoperative short-term death. There is contradiction between the results of RCTs and those of non-randomized clinical trials, which may result from the argument intensity, quantity and sample size bias of the included studies. The above conclusion should be proved by large-scale high-quality RCT results in future.
Objective [WTBZ]To assess the impact of dual antiplatelet therapy using aspirin and clopidogrel on postoperative bleeding and blood transfusion early after coronary artery bypass grafting (CABG). Methods [WTBZ]In this randomized controlled trial, 249 patients were randomly assigned to 2 groups after coronary artery bypass grafting from December 2007 to December 2008. Daily clopidogrel (75 mg) and aspirin (100 mg) were initiated in 124 patients (group AC) while aspirin (100 mg) alone was administered to 125 patients (group A). Antiplatelet therapy was initiated within 48h postoperatively. Demographic, operative, and postoperative data were compared between the two groups. Chest tube drainage and quantity of blood products used in both groups were recorded. The effects of the antiplatelet regimen on chest tube drainage were compared using a linear regression model. Results [WTBZ]No statistical difference of demographic, operative, and preoperative data was observed between the two groups （Pgt;0.05）. Chest tube drainage after patients received ntiplatelet agents was not significantly different between group A and group AC（495.00±270.89 ml vs. 489.25±316.68ml，t=0.146, P=0.884）. No statistical difference of cases of transfusion(81 cases vs. 91 cases，χ2=1.937, P=0.164) or quantity of red cells (2.51±2.88 U vs. 2.25±2.87 U, t=0.690, P=0.491) and plasma (195.45±300.88 ml vs. 223.01±238.68 ml,t=0.759, P=0.449) transfused was found between group A and group AC. No perioperative mortality, reexploration or extrathoracic bleeding occurred in either group. Early postoperative use of dual antiplatelet therapy was not associated with increased bleeding after coronary artery bypass grafting on multivariable analysis（r=2.297，95%CI:-64.526,69.121，P=0.946）. Conclusionpresent study suggests that according to a predefined administration protocol, dual antiplatelet therapy of aspirin and clopidogrel can safely be administered in the early postoperative period in CABG patients, without increasing the risk of bleeding complications.
Objective To systematically evaluate anti-platelet effect of clopidogrel influenced by CYP2C192,3 polymorphism in patients with cardiovascular diseases, in order to provide references for its safe medication. Methods Literature was retrieved in electronic databases covering EMbase, PubMed, The Cochrane Library, CBM and CNKI from establishment dates to November, 2011. Observational studies and clinical trials were included, cross-checked, assessed and pooled for meta-analysis. meta-analysis was performed using the software RevMan 5.1. Results A total of 13 articles including 14 trials (n=36 855) were included. The results of meta-analysis showed that: a) there was no significant difference in the incidences of cardiovascular events between CYP2C192,3 carriers and CYP2C191 carriers; b) the risk of stent thrombosis in CYP2C192,3 carriers was significantly higher than that in CYP2C191 carriers (Plt;0.000 1), and the relative risk of CYP2C192,3 carriers increased 92% within one month (Plt;0.000 1); c) as for bleeding events, there were no significant differences between CYP2C192,3 carriers and CYP2C191 carriers. Conclusion Compared with CYP2C191 carriers, CYP2C192,3 carriers have a higher risk of stent thrombosis in clopidogrel-treated patients, but there are few differences in cardiovascular and bleeding events between the two carriers. Therefore, CYP2C192,3 carriers with cardiovascular diseases and ready to receive PCT are suggested to pay more attention to stent thrombosis when using clopidogrel. We propose that patients with cardiovascular diseases and ready to receive PCT should have CYP2C19 tests to determine the use of antiplatelet drug (clopidogrel) to avoid thrombus.
Objective To perform a systematic review on the safety (i.g. cardiovascular, mortality and gastrointestinal bleeding) of clopidogrel versus clopidogrel combined with proton pump inhibitors (PPIs) for the patients with coronary heart disease. Methods Such databases as The Cochrane Library, PubMed, EMbase, SSCI, VIP, CNKI, and CBM were searched from the date of their establishment to September 2010. The bibliographies of the retrieved articles were also checked. The data was extracted and evaluated by two reviewers independently. The RevMan 5.0 software was used for meta-analyses. Results A total of 29 studies were included. The results of meta-analyses showed that the use of clopidogrel combined with PPIs was associated with increasing the risk of cardiovascular events (RR=1.27, 95%CI 1.09 to 1.47), as well as myocardial infarction (RR=1.45, 95% CI 1.20 to 1.76), total mortality (RR=1.23, 95%CI 1.06 to 1.43), and rethrombosis (RR=1.37, 95%CI 1.01 to 1.86). However, there was no enough evidence to reach the conclusion that the combination use could benefit the situation of gastrointestinal bleeding (RR=0.84, 95%CI 0.47 to 1.50). Conclusion?Compared with clopidogrel, the combination use of clopidogrel and PPIs increases cardiovascular events, mortality, and the risks of myocardial infarction and rethrombosis. However, more clinical studies are required to assess the effect of reducing gastrointestinal bleeding.
ObjectiveTo observe the clinical effect of clopidogrel combined with Suxiao Jiuxin Pills on patients with acute coronary syndrome (ACS). MethodsNinety-seven patients with ACS diagnosed between January 2010 and December 2011 were divided into the treatment group (treated with clopidogrel combined with Suxiao Jiuxin Pills) (n=48) and the control group (treated with single clopidogrel) (n=49). One month was regarded as a treatment course. After one month, we observed the clinical effect, heart attacks frequency, ST segment changes and adverse reactions for the patients. ResultsThe total effective rate was 79.2% in the treatment group and was 51.0% in the control group. There was significant difference between the two groups (P<0.05). Heart attacks frequency and ST segment were reduced significantly in both the two groups after treatment (P<0.05). The curative effect in the treatment group was significantly better than that in the control group after treatment (P<0.05). ConclusionClopidogrel combined with Suxiao Jiuxin Pills have a better clinical effect in the treatment of ACS than single clopidogrel.
ObjectiveTo investigate the impact of clopidogrel resistance on the long-term prognosis in the elderly with acute coronary syndrome (ACS), as clopidogrel is widely used for secondary prevention in the patients with ACS, while studies on the relationship between clopidogrel resistance and long-term outcome in the elderly with ACS are limited. MethodsThree hundred elderly patients with ACS, aged from 70 to 95, with on average age of (81.3±6.4) years old, receiving clopidogrel (75 mg, once a day) over one month between January 2009 and December 2010 were followed up for major adverse cardiac events (MACE, including cardiac death, non-fatal re-myocardial infarction, angina, ischemia stroke/TIA, acute thrombosis and hemorrhage). Platelet aggregation was measured by light transmission aggregometry using adenosine diphosphate as a stimulus. According to the variation of platelet aggregation, the patients were divided into clopidogrel resistance group (<10%) and non-lopidogrel resistance group (≥10%). The median follow-up was 2 years. A Cox hazard proportional model was used to estimate time to outcome associated with clopidogrel resistance and MACE. ResultsThe incidence of clopidogrel resistance was 24.0% in our study population. Patients with diabetes, renal insufficiency, or a higher body mass index tended to have clopidogrel resistance. Compared with those patients without clopidogrel resistance, there was significantly increased MACE in patients with clopidogrel resistance (37.5%, 22.8%; P=0.032). Additionally, Cox hazard proportional model analysis demonstrated that clopidogrel resistance was an independently risk factor for MACE[HR=2.34, 95% CI (1.07, 4.57), P=0.016]. ConclusionDiabetes, renal insufficiency and high body max index are associated with clopidogrel resistance, which can predict the increased risk of MACE in elderly patients with ACS.
ObjectiveTo assess the inhibitory ability of sarpogrelate on neointimal hyperplasia of carotid artery in rat balloon-injuried model, and to compare the proliferation of vascular smooth muscle cell (VSMC) by monitoring the expression of proliferative cell nuclear antigen (PCNA). MethodsTwenty-four male SD rats (SPF, 8 weeks) were allocated prospectively and randomly into 3 groups: blank group, sarpogrelate group, and clopidogrel group. Each group included 8 rats. All the rats were fed high-fat diet for 1 week before the operation. No drug was fed in the blank group, and sarpogrelate 100 mg/(kg·d) or clopidogrel 20 mg/(kg·d) was fed in the sarpogrelate group or clopidogrel group respectively. The carotid artery of rat was dilated by the Forgarty balloon catheter. The rats were killed 2 weeks later and the samples were got in the balloon-injuried carotid arteries. Histomorphological analysis and immunohistochemical analysis were proceeded. The thickness ratio and area ratio of intima and media, the ratio of PCNA positive cells and PCNA absorbance were calculated among the three groups. ResultsCompared with the blank group, the average intimal thickness, average intimal area, thickness ratio of intima and media, area ratio of intima and media, PCNA absorbance, and ratio of PCNA positive cells were significant decreased in the sarpogrelate group (P < 0.001) and the clopidogrel group (P < 0.001), but which had no significant differences between the sarpogrelate group and the clopidogrel group (P > 0.05). There was no significant difference in the average media thickness or area among the 3 groups (P > 0.05). ConclusionSarpogrelate and clopidogrel could significantly reduce the thickness or area of intima, the absorbance of PCNA and the ratio of PCNA positive cells.
ObjectiveTo evaluate anti-platelet effect of clopidogrel influenced by CYP2C19*17 polymorphism in patients with cardiovascular disease. MethodsWe electronically searched EMbase, PubMed, The Cochrane Library, ClinicalTrials.gov, CNKI, CBM, WanFang Data and VIP databases for cohort studies about the anti-platelet effect of clopidogrel influenced by CYP2C19*17 polymorphism in patients with cardiovascular disease from inception to October 2012. Two reviewers independently screened studies according to the inclusion and exclusion criteria, extracted data and evaluated the methodological quality of the included studies. Then meta-analysis was performed using the software Rev-Man 5.2. ResultsA total of seven studies involving 12 116 patients were finally included. Three were 5 579 CYP2C19*17 carriers and 6 538 non-carriers. The results of meta-analyses showed that, compared with the CYP2C19*17 non-carriers, lower rate of cardiovascular events (OR=0.85, 95%CI 0.73 to 0.99, P=0.03) and higher bleeding events (OR=1.25, 95%CI 1.05 to 1.50, P=0.01) were found in the CYP2C19*17 carriers. ConclusionCYP2C19*17 carriers is with lower cardiovascular events and higher bleeding events than the CYP2C19*17 non-carriers.
ObjectiveTo systematically review the effectiveness and safety of aspirin-clopidogrel combined anti-platelet therapy after coronary artery bypass grafting (CABG). MethodsDatabases including The Cochrane Library (Issue 2, 2013), PubMed, EMbase, CBM, CNKI, WanFang Data and VIP were searched electronically from their inception to September 2013 for randomized controlled trials (RCTs) about aspirin-clopidogrel combined anti-platelet therapy after CABG. Two reviewers selected literature independently according to the inclusion and exclusion criteria. After data extraction and methological quality assessment of the included studies, meta-analysis was performed using RevMan 5.2 software. ResultsA total of six RCTs involving 901 patients were included, of which 449 cases were in the aspirin-clopidogrel group (A+C) and 452 cases were in the aspirin with or without placebo group (A+P). The results of meta-analysis showed that: compared with A+P, A+C significantly reduced occlusion rates of the saphenous vein graft (RR=0.59, 95% CI 0.43 to 0.80, P=0.000 6). But no significant difference was found between the two groups in occlusion rates of the left internal mammary artery graft (RR=0.88, 95% CI 0.35 to 2.18, P=0.78), radial artery graft (RR=0.43, 95% CI 0.13 to 1.46, P=0.18), pleural fluid drainage volume (MD=-1.68, 95%CI-48.69 to 45.32, P=0.94), incidence of major bleeding events (RR=1.20, 95% CI 0.39 to 1.65, P=0.75), major cardiovascular events (OR=0.81, 95% CI 0.38 to 1.72, P=0.58), and mortality within 30 days (RR=0.64, 95% CI 0.17 to 2.44, P=0.52). ConclusionIn reducing occlusion rates of the saphenous vein graft, the A+C group is more effective than the A+P group. Due to the limited quantity and quality of the included studies, the above conclusion still needs to be verified by carrying out more high-quality RCTs.
Objectives To systematically review the efficacy and safety of clopidogrel 600 mg and 300 mg loading dose in Chinese patients underwent percutaneous coronary intervention (PCI). Methods We searched The Cochrane Library, EMbase, PubMed, CNKI, WanFang Data, CBM and VIP databases to collect randomized controlled trials (RCTs) of the efficacy and safety of clopidogrel 600 mg and 300 mg loading dose in Chinese patients underwent PCI from inception to April, 2017. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Meta-analysis was then performed using Stata 14.0 software. Results A total of 10 RCTs involving 1 166 patients were included. The results of meta-analysis showed that: the 600 mg loading dose group had lower incidence rate of major adverse cardiovascular events (MACE) in comparison with the 300 mg loading dose group (RR=0.29, 95%CI 0.17 to 0.48, P<0.000 1). However, no significant difference was found in the incidence of major bleeding events within 30 days between two groups (RR=1.64, 95%CI 0.70 to 3.80,P=0.252). Conclusions The current evidence shows that in Chinese patients underwent PCI, administration of a 600 mg loading dose of clopidogrel is associated with a lower risk of MACE than is administration of a 300 mg loading dose of clopidogrel, without increasing major bleeding risk in 30 days. Due to limited quality and quantity of the included studies, more high quality studies are required to verify above conclusions.