Clopidogrel: a review of its use in the prevention of atherothrombosis

Clopidogrel is an ADP receptor antagonist that is indicated for the reduction of atherosclerotic events including myocardial infarction, ischaemic stroke and vascular death in patients with atherosclerosis manifested by recent stroke, myocardial infarction or established peripheral vascular disease. In the 19 185 patients enrolled in the multicentre, randomised double-blind CAPRIE study, the annual risk of the combined end-point of ischaemic stroke, myocardial infarction and death from vascular disease (vascular death) was significantly lower during treatment with clopidogrel 75 mg/day than aspirin 325 mg/day [5.3 vs 5.8%/year, respectively; relative risk reduction (RRR) 8.7%, p = 0.043] after a mean follow-up of 1.9 years. Clopidogrel provided even greater reductions in the risk of recurrent ischaemic events than aspirin in patients with a history of coronary artery bypass surgery, diabetes mellitus and in those receiving concomitant lipid-lowering therapy. Moreover there was a significant reduction in the incidence of hospitalisation in patients treated with clopidogrel. In a patient population (Saskatchewan, Canada) with a greater risk of ischaemic events than the CAPRIE study population, the number of patients needed to be treated with clopidogrel to prevent 1 ischaemic event was estimated to be 70 (vs 200 in the CAPRIE study). In randomised trials and registry surveys, clopidogrel 75 mg/day plus aspirin had similar efficacy (as measured by adverse cardiac outcomes) to ticlopidine 250mg twice daily plus aspirin during the 30 days after placement of intracoronary stents. Tolerability of clopidogrel was significantly better than ticlopidine in the randomised, double-blind CLASSICS study. Among patients treated with clopidogrel or aspirin in the CAPRIE study, the overall gastrointestinal tolerability of clopidogrel was generally better than that of aspirin; the frequency of gastrointestinal haemorrhage was significantly lower among patients treated with clopidogrel than aspirin. Diarrhoea, rash and pruritis were significantly more common with clopidogrel than aspirin. CONCLUSION: Clopidogrel was significantly more effective than aspirin in the prevention of vascular events (ischaemic stroke, myocardial infarction or vascular death) [corrected] in patients with atherothrombotic disease manifested by recent myocardial infarction, recent ischaemic stroke or symptomatic peripheral arterial occlusive disease [corrected] in the CAPRIE study. The overall tolerability profile of the drug was similar to that of aspirin, although gastrointestinal haemorrhage occurred significantly less often in clopidogrel recipients. The drug is widely used in combination with aspirin for the prevention of atherothrombosis after placement of intravascular stents, and available data suggest that this combination is as effective as ticlopidine plus aspirin for this indication.     

Efficacy and safety analysis of new P2Y12 inhibitors versus clopidogrel in patients with percutaneous coronary intervention: a meta-analysis

Objective:

New P2Y₁₂ inhibitors, classified as oral (prasugrel and ticagrelor) and intravenous (cangrelor and elinogrel) drugs, have shown improved antithrombotic effects compared with clopidogrel in patients with acute coronary syndrome (ACS) or patients undergoing percutaneous coronary intervention (PCI) in landmark trials. The purpose of this study was to perform a meta-analysis of randomized trials that compared new P2Y₁₂ inhibitors with clopidogrel to determine their efficacy and safety in patients undergoing PCI.

Methods:

Randomized controlled trials of at least 4 weeks, comparing new P2Y₁₂ inhibitors with clopidogrel in PCI, were identified using the electronic databases Cochrane Central Register of Controlled Trials, Medline, PubMed, Web of Science, and Google Scholar from January 1, 1980, to July 31, 2014.

Main outcome measures:

The primary efficacy endpoints were all-cause death and major adverse cardiovascular events (MACEs). The primary safety endpoint was thrombolysis in myocardial infarction (TIMI) major bleeding.

Results:

Twelve studies including 71,097 patients met the inclusion criteria. New P2Y₁₂ inhibitors significantly reduced all-cause death (odds ratio [OR]: 0.81; 95% confidence interval [CI] 0.73–0.90, p?p?p?p?=?0.03) and cardiovascular death (OR 0.82; 95% CI 0.73–0.92, p?=?0.001) compared with clopidogrel. There were no significant differences between stroke (OR 0.87; 95% CI 0.72–1.05, p?=?0.14) and major bleeding events (OR 1.22; 95% CI 0.99–1.52, p?=?0.06) between the new P2Y₁₂ inhibitor and clopidogrel groups.

Conclusion:

New P2Y₁₂ inhibitors decreased death in patients undergoing PCI compared with clopidogrel with a considerable safety and tolerability profile; however, the risk/benefit ratio of ischemic and bleeding events should be further investigated.     

Randomised clinical trial: rabeprazole plus aspirin is not inferior to rabeprazole plus clopidogrel for the healing of aspirin-related peptic ulcer

Aliment Pharmacol Ther 2011; 34: 519–525

Summary

Background Clopidogrel does not inhibit prostaglandin synthesis. As a result, clopidogrel’s incidence of peptic ulcer disease (PUD) and ulcer bleeding is lower than aspirin’s. Aim To compare the healing rate in aspirin‐related dyspeptic ulcer patients who were given proton pump inhibitor (PPI) plus aspirin or PPI plus clopidogrel. Methods Patients with aspirin‐related nonbleeding symptomatic ulcers were randomised to receive rabeprazole (20 mg/day) plus aspirin (100 mg/day) or rabeprazole (20 mg/day) plus clopidogrel (75 mg/day) for 12 weeks. The primary endpoint was the successful treatment of PUD as characterised by intention‐to‐treat at the end of therapy. Results Two hundred and eighteen patients (109 in the aspirin group and 109 in the clopidogrel group) were enrolled. There were no statistical demographic differences between the group that received aspirin and the group that received clopidogrel. The PUD treatment success rate was also statistically equal between the clopidogrel and aspirin groups (86.2% vs. 90.0%, P = 0.531). Neither group experienced ulcer‐related bleeding. Multivariate logistic regression analysis showed that large ulcer size (>10 mm) (OR: 6.29, 95% CI: 2.58–15.37) and past history of PUD (OR: 3.69, 95% CI: 1.24–10.97) were important predictors of unsuccessful therapy for aspirin‐related PUD. Conclusions Rabeprazole plus aspirin is not inferior to rabeprazole plus clopidogrel in treating aspirin‐related symptomatic PUD. Large ulcer size (>10 mm) and past history of PUD are important predictors of unsuccessful therapy (NCT 01037491).     

Clopidogrel Bisulfate

Clopidogrel bisulfate (hereafter, clopidogrel), a selective inhibitor of ADP-induced platelet aggregation, is approved for the reduction of atherothrombotic events in patients with ST-segment elevation myocardial infarction (STEMI). In COMMIT/CCS-2, a well designed trial in 45,852 adult patients with STEMI, relative to aspirin alone, clopidogrel 75 mg/day plus aspirin treatment significantly reduced the risk of both coprimary endpoints: the composite endpoint of reinfarction, stroke, or death from any cause and the risk of death from any cause. Based on the findings of this trial, treating 1000 patients for approximately 2 weeks with clopidogrel is associated with nine fewer patient deaths, reinfarctions, or strokes during treatment. In CLARITY-TIMI 28, a well designed supportive study in 3491 adult patients with STEMI, clopidogrel plus aspirin reduced the odds that a composite primary endpoint event of an occluded infarct-related artery, recurrent myocardial infarction, or death from any cause would occur versus aspirin plus placebo. Clopidogrel treatment was generally well tolerated in these clinical trials, with no significant between-group difference in the rate of major bleeding in either trial. Experience in other patient populations (e.g. those with recent myocardial infarction, recent ischemic stroke, or established peripheral arterial disease) has shown that longer-term (< or =3 years) clopidogrel monotherapy is generally well tolerated.     

Antiplatelet therapy in peripheral arterial disease

Antiplatelet therapy significantly reduces the incidence of vascular death, nonfatal myocardial infarction, and nonfatal stroke in patients with peripheral arterial disease (PAD) and intermittent claudication, in patients undergoing peripheral grafting, in patients undergoing peripheral angioplasty, and in patients with carotid disease. Aspirin, aspirin plus dipyridamole, ticlodipine, and clopidogrel have been shown to be efficacious in the treatment of PAD. Data from the Clopidogrel versus Aspirin in Patients at Risk for Ischaemic Events (CAPRIE) trial demonstrated in 11,592 patients with PAD that patients randomized to clopidogrel 75 mg daily had a 24% significant (p=0.0028) reduction in vascular death, nonfatal myocardial infarction, and nonfatal stroke than patients randomized to aspirin 325 mg daily. These data favor the use of clopidogrel in patients with PAD.     

Comparative safety and tolerability of clopidogrel and aspirin: results from CAPRIE. CAPRIE Steering Committee and Investigators. Clopidogrel versus aspirin in patients at risk of ischaemic events.

OBJECTIVE: The objective of this study was to provide a comprehensive comparison of the long term safety and tolerability of clopidogrel, a new adenosine diphosphate (ADP) receptor antagonist that inhibits platelet activation induced by ADP, and aspirin (acetylsalicylic acid). PATIENTS AND METHODS: The study population comprised 19,185 patients with symptomatic atherosclerosis manifested as recent ischaemic stroke, recent myocardial infarction or symptomatic peripheral arterial disease. Patients were randomised to receive clopidogrel 75 mg/day or aspirin 325 mg/day for a minimum of 1 year and a maximum of 3 years. RESULTS: Compared with aspirin, clopidogrel reduced the combined risk of ischaemic stroke, myocardial infarction or vascular death by 8.7% (p = 0.043). The incidence of early permanent discontinuations of the study drug due to adverse events was almost identical in both treatment groups (11.94% for clopidogrel vs 11.92% for aspirin). Reported neutropenia was similar in the clopidogrel and aspirin groups (0.10 vs 0.17%, respectively) with corresponding rates (0.05 vs 0.04%, respectively) for severe neutropenia. Thrombocytopenia was identical in the clopidogrel and aspirin groups (0.26%), with the rates of severe thrombocytopenia being 0.19 vs 0.10%, respectively. None of these observed differences was statistically significant. The overall incidence of haemorrhagic events did not differ statistically significantly between treatment groups (9.27% for clopidogrel vs 9.28% for aspirin; p = 0.98). There was a trend towards a lower incidence of intracranial haemorrhage in the clopidogrel group (0.31%) compared with the aspirin group (0.42%). Any reported gastrointestinal haemorrhage was significantly less frequent with clopidogrel (1.99%) than with aspirin (2.66%) [p < 0.002]. The corresponding data for severe gastrointestinal bleeding were 0.49 vs 0.71%; p < 0.05. Overall, there were significantly fewer gastrointestinal adverse events with clopidogrel than with aspirin (27.1 vs 29.8%; p < 0.001), with less abdominal pain, dyspepsia, constipation, or peptic, gastric, or duodenal ulceration with clopidogrel. Diarrhoea was significantly more common in the clopidogrel group (4.46 vs 3.36%; p < 0.001), although the incidence of severe diarrhoea (0.23 vs 0.11%) was low and was not significantly different between groups. There were significantly more patients with rash in the clopidogrel group (6.0%) compared with the aspirin group (4.6%) [p < 0.001]. However, these events were generally mild and transient in nature. CONCLUSION: Given the favourable benefit/risk ratio, clopidogrel represents a clinically important advance in the treatment of patients with manifest atherosclerotic disease.     

Long-Term Benefit of Statin Therapy Initiated during Hospitalization for an Acute Coronary Syndrome

OBJECTIVE: This study sought to determine if the initiation of statin (HMG-CoA reductase inhibitor) therapy during acute coronary syndromes reduces long-term mortality and other adverse cardiac outcomes. BACKGROUND: Initiation of statin therapy during acute coronary syndromes has not been shown to reduce mortality, myocardial infarction or stroke within 4 months of follow-up. METHODS: Clinical trials that randomized patients with acute coronary syndromes to early statin therapy compared with less intensive lipid reduction (placebo/lower-dose statin/usual care), and reported long-term outcomes were included for analysis. RESULTS: In all, there were seven studies (L-CAD, PTT, FLORIDA, Colivicchi et al., PROVE-IT, ESTABLISH, and A-to-Z) with 9553 patients who started statin therapy within 12 days of hospital presentation. The incidence of all-cause mortality was 3.4% in the statin group versus 4.6% in the less intensive lipid reduction group over a weighted mean follow-up of 22.9 months (relative risk [RR] 0.74; 95% CI 0.61, 0.90; p = 0.003). The number of patients needed to treat to prevent one death was 84 patients. Similarly, the incidence of cardiovascular mortality in the statin versus the less intensive lipid reduction group was 2.4% versus 3.3% (RR 0.74; 95% CI 0.58, 0.93; p = 0.010), unstable angina 4.1% versus 5.0% (RR 0.81; 95% CI 0.68, 0.98; p = 0.027), revascularization 11.2% versus 12.9% (RR 0.86; 95% CI 0.78, 0.96; p = 0.006), stroke 1.1% versus 1.2% (RR 0.90; 95% CI 0.62, 1.30; p = 0.56), and myocardial infarction 6.6% versus 7.0% (RR 0.94; 95% CI 0.81, 1.09; p = 0.41). CONCLUSIONS: The benefit of early initiation of statin therapy during acute coronary syndromes slowly accrues over time so that a survival advantage is seen around 24 months. Relatively few patients need to be treated to prevent one death over this time period. Furthermore, this approach significantly reduces unstable angina and the need for revascularization.     

Clopidogrel

? Clopidogrel is a selective inhibitor of ADP-induced platelet aggregation.

? A large, multicenter, randomized study in 12562 patients with acute coronary syndromes without ST-segment elevation demonstrated that treatment with clopidogrel (loading dose of 300mg followed by once daily treatment with 75mg) in addition to standard therapy including aspirin (75 to 325 mg/day) significantly reduced the risk of the combined endpoint of cardiovascular death, myocardial infarction or stroke compared with treatment with standard therapy. Furthermore, the composite risk of these outcomes or refractory ischemia was also significantly reduced in patients treated with clopidogrel plus aspirin. The effects of clopidogrel were independent of background treatment with cardiovascular medications and/or interventions.

? The risk of severe ischemia, recurrent angina or heart failure was also significantly reduced in patients receiving clopidogrel plus aspirin. There was also a significant reduction in the need for coronary revascularization during the initial period of hospitalization.

? In patients undergoing percutaneous coronary intervention (PCI), the relative risk of the combined endpoint of cardiovascular death, myocardial infarction or urgent target-vessel revascularization within 30 days of the intervention was significantly reduced. Moreover, the relative risk of the single endpoint of myocardial infarction within 30 days of PCI was significantly in favor of clopidogrel-treated patients.

? Hemorrhagic events (both major and minor) were significantly more frequent in patients with acute coronary syndromes receiving treatment with clopidogrel plus aspirin than in patients treated with aspirin alone. This was largely attributable to an increased incidence in the rate of gastrointestinal hemorrhage and bleeding at the site of arterial puncture. However, there was no difference between the two groups in the incidence of bleeding episodes that were considered to be life-threatening.

     

阿司匹林抵抗的急性冠脉综合征患者加用替罗非班治疗的疗效及安全性探讨

目的评价血小板糖蛋白Ⅱb／Ⅲa（GPⅡb／Ⅲa）受体拈抗剂替罗非班应用于阿司匹林抵抗（AR）的急性冠脉综合征（ACS）患者的疗效及安全性。方法128例AR的ACS（包括不稳定性心绞痛和非Q波心肌梗塞）随机分为替罗非班组和对照组,对照组常规联合应用阿司匹林和氯吡格雷治疗,替罗非班组加用替罗非班治疗。观察用药后36小时和30天的不良心血管事件及副反应的发生情况。结果用药后36小时两组患者均未出现死亡及靶血管再次重建。用药后36小时实验组未出现心绞痛及心梗,对照组2例出现心绞痛,无心梗发生。用药后30天实验组无心绞痛发作,无心梗发作,对照组5例出现心绞痛,2例出现心梗。用药后36小时,替罗非班组出现2例牙龈出血,对照组无出血事件发生。用药后30天两组均无出血事件发生。两组均无颅内出血及消化道大出血,无血小板减少发生。两组的出血事件及血小板减少的副反应发生率无统计学意义（P〉0．05）。结论阿司匹林抵抗的急性冠脉综合征患者加用替罗非班治疗可明显降低心绞痛及心梗的发生率,并不增加急性冠脉综合征患者出血及血小板减少的发生率．值得临床推广应用。     

PCI 术后三联与双联抗凝策略疗效比较的 Meta 分析

目的 比较双联 （阿司匹林、 氯吡格雷） 与三联 （阿司匹林、 氯吡格雷、 华法林） 抗血小板聚集方案治疗同时 有应用口服抗凝药物（OAC）及双联抗血小板聚集药物（DAPT）指征患者的疗效与安全性。方法 检索 PubMed、 Cochrane、 Embase 数据库, 收集 1966 年 1 月—2016 年 4 月发表的有 OAC 及 DAPT 应用指征的患者抗凝药物使用的 疗效和安全性比较的研究, 同时辅以手检纳入文献的参考文献。对文献进行筛选、 质量评价与资料提取, 采用 RevMan 5.1 软件进行 Meta 分析, 主要终点事件为全因死亡率, 次要终点事件包括缺血性卒中、 主要出血事件、 心肌 梗死以及支架内血栓形成。结果 共纳入 16 项研究, 共 7 083 例患者（三联 3 330 例, 双联 3 753 例）, 中位随访期 1.6 年, 平均年龄 73.2 岁。Meta 分析显示： 三联抗凝与双联抗凝策略相比, 全因死亡率[OR（95%CI） =0.94（0.79～ 1.13）, P=0.54]、 心肌梗死发生率[OR（95%CI） =1.21（0.92～1.59）, P=0.16]、 支架内血栓事件发生率[OR（95%CI） =1.02 （0.55～1.90）, P=0.94]差异均无统计学意义, 相对于采取双联抗凝策略的患者, 应用三联抗凝策略能降低缺血性卒中 风险[OR（95%CI） =0.44（0.30～0.63）, P＜0.001], 增加主要出血事件风险[OR（95%CI） =1.31（1.07～1.61）, P=0.008]。 结论 针对同时具有应用 OAC 及 DAPT 指征的患者, 使用三联抗凝策略在降低卒中风险的同时会增加出血的风险。     

不停跳冠脉旁路移植术前停用氯吡格雷对出血风险及短期预后的影响

目的:探讨不停跳冠脉旁路移植术(off-pump coronary artery bypass grafting,OPCABG)术前停用氯吡格雷对围术期出血风险及预后的影响.方法:本研究是一项前瞻性队列研究.纳入接受阿司匹林联合氯吡格雷治疗且拟行OPCABG的患者.根据术前停用氯吡格雷时间分为3组:(1)停药＜72 h...     

Antiplatelet therapy for the prevention of recurrent stroke and other serious vascular events: a review of the clinical trial data and guidelines

ABSTRACT

Background: One strategy of reducing the burden of stroke is the prevention of recurrent stroke, following an initial ischaemic stroke or transient ischaemic attack (TIA) of arterial origin, by means of antiplatelet therapy.

Scope: This review article surveys and discusses the current clinical trial data and guidelines for the use of antiplatelet therapy in the prevention of recurrent stroke/TIA of arterial origin (not stroke due to atrial fibrillation). Based on the latest available evidence, a new antiplatelet treatment algorithm for the long-term treatment of patients following atherothromboembolic ischaemic stroke or TIA is proposed.

Findings: Meta-analyses of randomised clinical trials in patients with TIA and ischaemic stroke of arterial origin indicate that, compared with control, the relative risk reduction (RRR) for recurrent stroke and other serious vascular events is 13% (95% confidence interval [CI] 6% to 19%) with aspirin, 13% (4% to 21%; p = 0.046) with dipyridamole and 34% (24% to 43%) with the combination of aspirin and dipyridamole. Compared with aspirin, the relative risk of recurrent stroke and other serious vascular events is reduced by 7.3% (95% CI –5.7% to 18.7%) with clopidogrel and 18% (9% to 26%; p = 0.0003) with the combination of aspirin and dipyridamole. The combination of aspirin and clopidogrel is not significantly more effective in preventing serious vascular events than clopidogrel alone (RRR 6.4%; –4.6% to 16.3%) in the long-term treatment of patients with previous ischaemic stroke and TIA, mainly because of a cumulative excess of bleeding complications. The relative risks and benefits of long-term treatment with clopidogrel and the combination of aspirin and dipyridamole are being compared in an ongoing large clinical trial (PRoFESS). Current Australian therapeutic guidelines for antiplatelet therapy among patients with TIA and ischaemic stroke of arterial origin have incorporated important new findings from recently published clinical trials and recommend aspirin or the combination of dipyridamole plus aspirin as the preferred long-term antiplatelet therapy.

Conclusion: Whilst awaiting the results of the PRoFESS trial, the combination of dipyridamole plus aspirin is the preferred antiplatelet regimen to reduce the risk of recurrent vascular events among patients with TIA and ischaemic stroke of arterial origin.     

Clopidogrel: a CURE in acute coronary syndromes?

The standard approach to preventing acute coronary syndromes (ACSs)has been to inhibit platelet aggregation with aspirin and to inhibit blood coagulation with low molecular-weight heparin (LMWH). Even with this combination there is still a substantial short and long-term cardiovascular risk. The Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) trial [1] compared clopidogrel plus aspirin against aspirin alone in patients with ACSs. The clopidogrel regimen was a loading dose of 300 mg p.o. followed by 75 mg/day and the recommended dose of aspirin was 75 - 325 mg/day. The first primary outcome was a composite of death from cardiovascular causes, non-fatal myocardial infarction (MI) or stroke and this occurred significantly less often in the clopidogrel than the placebo group (9.3 vs. 11.4%). Although there were more clopidogrel patients with life-threatening bleeding (clopidogrel 2.2%, placebo 1.8%), this represented GI haemorrhages and bleeding at sites of arterial puncture rather than fatal bleeding. This trial suggests a role for clopidogrel in the long-term treatment of ACSs.     

Clopidogrel hydrogen sulphate for atrial fibrillation

Introduction: Atrial fibrillation is a common cardiac rhythm abnormality with a considerable cardiovascular disease burden worldwide. It is an independent major risk factor for stroke. Stroke prevention with anticoagulation or antiplatelet agents has been an important area of clinical research. Warfarin is the most widely used antithrombotic therapy for stroke prophylaxis for last several years, and now dabigatran (150 mg b.i.d.) is more effective than warfarin in stroke prevention in individuals at increased of stroke. In addition, several studies have evaluated the efficacy of clopidogrel for stroke prophylaxis either alone or in combination with aspirin.

Areas covered: This review summarizes the key findings of the trials looking at the efficacy of clopidogrel in stroke prevention. A literature search was performed using PubMed and Google Scholar. The trials that evaluated the efficacy of clopidogrel in preventing atherothrombotic events or stroke were also included.

Expert opinion: Clopidogrel prevents more vascular events, including stroke, in patients with a recent myocardial infarction, stroke or peripheral vascular disease than aspirin. Combination of clopidogrel and aspirin provides a greater reduction of stroke than aspirin or clopidogrel monotherapy, but at an increased risk of bleeding. Dual antiplatelet therapy (clopidogrel and aspirin) is inferior to warfarin in primary stroke prevention for patient with atrial fibrillation and thus should be considered for stroke prophylaxis only in patients ineligible for warfarin. However, with the advent of newer agents, like direct thrombin inhibitors and Factor Xa inhibitors, the role of antiplatelet therapy for stroke prevention in atrial fibrillation remains unclear.     

Clopidogrel hydrogen sulphate for atrial fibrillation

INTRODUCTION: Atrial fibrillation is a common cardiac rhythm abnormality with a considerable cardiovascular disease burden worldwide. It is an independent major risk factor for stroke. Stroke prevention with anticoagulation or antiplatelet agents has been an important area of clinical research. Warfarin is the most widely used antithrombotic therapy for stroke prophylaxis for last several years, and now dabigatran (150 mg b.i.d.) is more effective than warfarin in stroke prevention in individuals at increased of stroke. In addition, several studies have evaluated the efficacy of clopidogrel for stroke prophylaxis either alone or in combination with aspirin. AREAS COVERED: This review summarizes the key findings of the trials looking at the efficacy of clopidogrel in stroke prevention. A literature search was performed using PubMed and Google Scholar. The trials that evaluated the efficacy of clopidogrel in preventing atherothrombotic events or stroke were also included. EXPERT OPINION: Clopidogrel prevents more vascular events, including stroke, in patients with a recent myocardial infarction, stroke or peripheral vascular disease than aspirin. Combination of clopidogrel and aspirin provides a greater reduction of stroke than aspirin or clopidogrel monotherapy, but at an increased risk of bleeding. Dual antiplatelet therapy (clopidogrel and aspirin) is inferior to warfarin in primary stroke prevention for patient with atrial fibrillation and thus should be considered for stroke prophylaxis only in patients ineligible for warfarin. However, with the advent of newer agents, like direct thrombin inhibitors and Factor Xa inhibitors, the role of antiplatelet therapy for stroke prevention in atrial fibrillation remains unclear.     

阿司匹林抵抗的急性冠脉综合征患者加用替罗非班治疗的疗效及安全性探讨

目的评价血小板糖蛋白Ⅱh／Ⅲa（GPⅡb／Ⅲa）受体拮抗剂替罗非班应用于阿司匹林抵抗（AR）的急性冠脉综合征（ACS）患者的疗效及安全性。方法128例AR的ACS（包括不稳定性心绞痛和非Q波心肌梗塞）随机分为替罗非班组和对照组,对照组常规联合应用阿司匹林和氯吡格雷治疗,替罗非班组加用替罗非班治疗。观察用药后36小时和30天的不良心血管事件及副反应的发生情况。结果用药后36小时两组患者均未出现死亡及靶血管再次重建。用药后36小时实验组未出现心绞痛及心梗,对照组2例出现心绞痛,无心梗发生。用药后30天实验组无心绞痛发作,无心梗发作,对照组5例出现心绞痛,2例出现心梗。用药后36小时,替罗非班组出现2例牙龈出血,对照组无出血事件发生。用药后30天两组均无出血事件发生。两组均无颅内出血及消化道大出血,无血小板减少发生。两组的出血事件及血小板减少的副反应发生率无统计学意义（P〉0．05）。结论阿司匹林抵抗的急性冠脉综合征患者加用替罗非班治疗可明显降低心绞痛及心梗的发生率,并不增加急性冠脉综合征患者出血及血小板减少的发生率,值得临床推广应用。     

Aspirin and esomeprazole are superior to clopidogrel in preventing recurrent ulcer bleeding

Although low-dose aspirin is commonly used as the antiplatelet agent to prevent ischaemic events such as myocardial infarction and stroke, clopidogrel is probably superior at preventing ischaemic events. For patients who cannot tolerate aspirin, adding a proton pump inhibitor or substituting clopidogrel are options. Patients with endoscopy-confirmed ulcer healing were assigned to clopidogrel 75 mg/day or aspirin 80 mg/day and esomeprazole 20 mg b.i.d. for 12 months. There were 14 confirmed cases of recurrent ulcer bleeding, with 13 being from the 161 patients taking clopidogrel and 1 from the 159 patients taking aspirin plus esomeprazole. This trial has clearly shown that the combination of aspirin and esomeprazole is superior to clopidogrel in preventing recurrent ulcer bleeding. A more interesting study may have been to compare the effects of aspirin and clopidogrel in the presence of esomeprazole in patients with a history of ulcers.     

Aspirin and esomeprazole are superior to clopidogrel in preventing recurrent ulcer bleeding

Although low-dose aspirin is commonly used as the antiplatelet agent to prevent ischaemic events such as myocardial infarction and stroke, clopidogrel is probably superior at preventing ischaemic events. For patients who cannot tolerate aspirin, adding a proton pump inhibitor or substituting clopidogrel are options. Patients with endoscopy-confirmed ulcer healing were assigned to clopidogrel 75 mg/day or aspirin 80 mg/day and esomeprazole 20 mg b.i.d. for 12 months. There were 14 confirmed cases of recurrent ulcer bleeding, with 13 being from the 161 patients taking clopidogrel and 1 from the 159 patients taking aspirin plus esomeprazole. This trial has clearly shown that the combination of aspirin and esomeprazole is superior to clopidogrel in preventing recurrent ulcer bleeding. A more interesting study may have been to compare the effects of aspirin and clopidogrel in the presence of esomeprazole in patients with a history of ulcers.     

Role of aspirin in the primary prevention of cardiovascular disease in diabetes mellitus: a meta-analysis

Objective: To evaluate the benefits of aspirin in people with diabetes mellitus for the primary prevention of cardiovascular disease.

Research design/methods: We searched MEDLINE and Cochrane database for randomized, controlled trials of aspirin in people with diabetes and no cardiovascular disease. Relative risks were determined using random-effects meta-analysis.

Main outcome measures: Risk reduction of aspirin compared with control groups for major cardiovascular events.

Results: Six trials consisting of 7374 patients with diabetes showed no benefits of aspirin compared with non-aspirin users with regard to overall mortality, risk reduction (relative risk (RR) = 0.96, 95% CI 0.78 – 1.18, p = 0.71), major cardiovascular events (RR = 0.90, 95% CI 0.78 – 1.05, p = 0.17) and myocardial infarction (RR = 0.95, 95% CI 0.76 – 1.18, p = 0.63). Risk of major bleeding in the aspirin compared with the non-aspirin group was not significant (RR = 2.49, 95% CI 0.70 – 8.84, p = 0.16).

Conclusions: Aspirin therapy did not reduce the risk of cardiovascular events. Existing trials were limited by small patient numbers and low cardiovascular event rates. The use of aspirin cannot be routinely recommended for primary prevention of cardiovascular events in diabetes.     

Efficacy and safety of abciximab in combination with cilostazol in patients undergoing stenting

OBJECTIVE: To evaluate the short- and long-term efficacy and safety of abciximab and cilostazol in patients with acute MI and unstable angina undergoing intracoronary stenting. METHODS: Acute-phase (7 and 30 days), 6-month and long-term composite outcomes involving death, myocardial infarction or urgent target vessel revascularization (TVR) together with other outcomes (composite outcomes involving death, MI and elective TVR with restenosis and stroke) were evaluated retrospectively in a total of 175 patients. Safety outcomes were assessed using data on the incidence of bleeding and thrombocytopenia at Day 7 and Day 30. RESULTS: Of 175 patients, 83 (47.4%) patients received abciximab. At 7 and 30 days, the composite outcome for the group treated with cilostazol alone and that treated with abciximab in combination with cilostazol did not differ significantly. The composite outcomes at 6 months and 1 year were significantly lower in the abciximab plus cilostazol group (relative risk 0.35, 95% Cl 0.13 - 0.90, relative risk 0.28, 95% CI 0.10 -0.78, respectively). The incidence of major bleeding at the access-site and in the gastrointestinal tract and minor bleeding were significantly higher in the group receiving abciximab plus cilostazol group at 7 days (relative risk 3.33, 95% CI 1.66 - 6.65, relative risk 9.98, 95% CI 1.29 - 77.07, relative risk 1.96, 95% CI 1.06 - 3.62, respectively) and at 30 days (relative risk 3.33, 95% CI 1.66 - 6.65, relative risk 5.54, 95% CI 1.25 - 24.56, relative risk 1.96, 95% CI 1.06 - 3.62, respectively). CONCLUSION: The combination of abciximab and cilostazol showed an improvement in major cardiac incidents at 6 months and 1 year of the treatment when compared to the group receiving cilostazol alone. However, abciximab did not improve the incidence of death but increased the risk of bleeding complications.