Antiplatelet agents and randomized trials

Patients who have transient ischemic attack (TIA) or ischemic stroke are at a high risk of having a first or recurrent stroke. The annual risk is between 5% and 15%; the risk is highest in the first 48 hours following a TIA and highest in the first 7 days following an ischemic stroke. Secondary prevention includes antithrombotic therapy, treatment of risk factors, and interventional treatment of carotid stenosis. Antithrombotic options can include antiplatelet drugs such as aspirin, aspirin plus extended-release dipyridamole (ER-DP), clopidogrel, or clopidogrel plus aspirin. Oral anticoagulation is used in patients with a cardiac source of embolism such as atrial fibrillation. Aspirin monotherapy offers a modest risk reduction for recurrent stroke and for the combined endpoint of nonfatal stroke, myocardial infarction (MI), and vascular death. The combination of ER-DP and aspirin was shown to be superior to aspirin monotherapy in several trials. Clopidogrel is superior to aspirin in high-risk patients suffering from stroke, MI, or peripheral arterial disease. The combination of clopidogrel plus aspirin is not superior to aspirin or clopidogrel monotherapy and carries a significantly higher bleeding risk. The combination might offer benefit in short-term secondary prevention after TIA or stroke. Another ongoing trial is currently investigating the possible benefit and side effects of aspirin plus ER-DP versus clopidogrel in secondary stroke prevention.     

Antiplatelet drugs for prevention of cerebral ischemic accidents]

Antiplatelet (AP) drugs play a major role in stroke prevention. Aspirin (50-1300 mg), ticlopidine (500 mg), clopidogrel (75 mg) and dipyridamole (400 mg) are effective in secondary prevention of atherothrombotic brain infarcts. Aspirin has been the most extensively studied drug and remains the most cost-effective one. The optimal dose is still debated; doses between 100 and 300 mg are the most widely used. The preventive efficacy of aspirin is already present at the acute phase of cerebral infarct. In primary prevention, aspirin nearly halves the risk of myocardial infarction but does not reduce that of stroke. Cardiac diseases with a high embolic risk require the use of oral anticoagulation. In non valvular atrial fibrillation, the choice of antithrombotic drugs depends on risk stratification: oral anticoagulants are indicated in high risk subjects whereas aspirin is recommended in low risk subjects and when oral anticoagulants are contraindicated. Studies with new associations of AP and with new drugs are required to increase the yield of the antiplatelet approach in high risk subjects; this should be done in parallel with efforts to detect and to treat the vascular risk factors associated with the development of a mass approach for stroke primary prevention.     

EBM of cerebral infarction: message from mega-studies]

A meta-analysis by the Antithrombotic Trialists' Collaboration showed significant reduction of vascular events including stroke. MI, and vascular death by antiplatelet therapy in high risk patients with obstructive vascular disease. Low dose aspirin of 75 to 150 mg was most effective and its very low dose below 75 mg was not proven effective. Cilostazol significantly reduced the risk of recurrence in Japanese patients with ischemic stroke, mostly lacunar stroke. Large randomized controlled trials (RCTs) such as MATCH, ACTIVE, and CHARISMA are ongoing to see an effect of aspirin plus clopidogrel. Among patients with non-valvular atrial fibrillation (NVAF), warfarin is recommended in patients at age over 75 years, and those with history of stroke or TIA, hypertension, congestive heart failure, diabetes or coronary heart disease, while aspirin can be alternative in patients without any of these risk factors of stroke. Target INR of 2.0 to 3.0 is recommended in these NVAF patients, although lower INR of 1.6 to 2.5 is recommended to avoid hemorrhagic stroke in elderly patients with NVAF. SPORTIF was conducted to compare ximelagatran, an oral thrombin inhibitor, with warfarin in NVAF patients with risk factors, and the result showed a comparable efficacy and safety of ximelagatran. WARSS did not show any efficacy of warfarin over aspirin in any subtypes of ischemic stroke patients without NVAF, acute MI, left ventricular thrombi, or prosthetic heart valve. PICSS, a substudy of WARSS, also did not show any efficacy of warfarin over aspirin in stroke patients with patent foramen ovale (PFO), although warfarin might be recommended in PFO patients with deep vein thrombosis.     

Clinical consequences of aspirin and clopidogrel resistance: an overview

The aim of this review is to introduce the concept of personalized medicine in secondary stroke prevention with antiplatelet medication. In the last years, many studies have been conducted regarding aspirin resistance and genotyping of clopidogrel metabolism. A review of the currently published data on this issue emphasizes the importance of focusing on the individualizing approach in antiplatelet therapy to achieve maximal therapeutic beneficial effect. However, many authors suggest that, before new information from ongoing trials become available, good clinical practice should dictate the use of low dose of aspirin that was shown to be effective in the prevention of stroke and death in patients with ischemic cerebrovascular disease, because higher doses do not have significantly better efficacy than lower doses in secondary stroke prevention, but lower‐dose aspirin is associated with less side effects. On the other hand, many factors are associated with clopidogrel resistance, and recent genetic studies showed that the CYP2C19*2 genotype (loss‐of‐function allele) is related to poor metabolism of clopidogrel, but larger studies are needed to definitively confirm or rule out the clinical significance of this genetic effect. The aim of personalized approach in secondary stroke prevention is to take the most appropriate medicine in the right dose in accordance with the clinical condition of the patient and associated risk factors.     

阿加曲班治疗急性缺血性卒中的临床应用

阿加曲班是一种直接凝血酶抑制剂,具有起效较快、作用时间短、出血倾向小、无免疫源性等优点,能够有效阻止血栓进展,防止继发微血栓形成。国内外多项研究证实,阿加曲班能有效改善急性缺血性卒中患者的神经系统症状和日常活动能力,且对急性动脉粥样硬化性卒中和心源性卒中均有治疗作用,此外,阿加曲班与阿司匹林、奥扎格雷等抗血小板药物以及肝素相比疗效更显著,具有较高的安全性,同时由于作用机制不同,阿加曲班与阿司匹林、氯吡格雷等抗血小板药物、重组组织型纤溶酶原激活物(recombinant tissue plasminogen activator,rt-PA)联合治疗可能发挥协同作用。本文就阿加曲班在急性缺血性卒中的临床应用做一系统性综述。     

Benefit of ADP receptor antagonists in atherothrombotic patients: new evidence

In the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE) trial, clopidogrel showed a statistically significant superiority over aspirin in the prevention of ischaemic stroke, myocardial infarction and vascular death in patients with symptomatic atherosclerosis. More recently, post-hoc analysis of the data also showed that repeat hospitalization for ischaemic or bleeding events was decreased with clopidogrel compared with aspirin. Complementary analyses show that the benefit of clopidogrel over aspirin is amplified in a large population at very high risk of further atherothrombotic events (diabetics, patients with high cholesterol, and patients with previous manifestations of atherothrombosis). A potential clinically useful advantage of clopidogrel is its low propensity for adverse interaction with angiotensin-converting enzyme (ACE) inhibitors, contrary to what may be seen with aspirin, as observed in a post-hoc CAPRIE analysis. The putative aspirin-ACE inhibitor interaction is being tested prospectively in the Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial - a randomized comparison of warfarin, clopidogrel and aspirin in patients with chronic heart failure. The good gastrointestinal tolerance of clopidogrel seen in CAPRIE has been further demonstrated in a study in healthy volunteers where there was a markedly lower gastroduodenal erosion score after 8 days' administration of clopidogrel 75 mg/day compared with aspirin 325 mg/day (p < 0.001). Following the positive findings obtained with clopidogrel plus aspirin in the Clopidogrel Aspirin Stent International Cooperative Study (CLASSICS) trial, other studies of clopidogrel plus aspirin have been initiated or are planned. These include Management of Atherothrombosis with Clopidogrel in High-risk patients (MATCH), a randomized comparison of clopidogrel plus aspirin versus clopidogrel in high-risk patients with recent stroke or transient ischaemic attack.     

Future perspectives for optimizing oral antiplatelet therapy

Secondary prevention of stroke and other manifestations of atherothrombosis is essential if the burden of disease associated with these events is to be reduced. Therefore, it is important to identify patients most likely to benefit from antiplatelet therapy. There is a good rationale for combining antiplatelet agents with different modes of action, since different signalling pathways contribute to platelet activation. Based on the promising results obtained with an adenosine diphosphate receptor antagonist-aspirin combination in coronary stenting, several additional trials with clopidogrel plus aspirin are ongoing. They include CURE (Clopidogrel in Unstable angina to prevent Recurrent Events, in unstable angina and non-Q-wave myocardial infarction) and COMMIT (in acute myocardial infarction), which compare clopidogrel with placebo in patients receiving aspirin, and CREDO (Clopidogrel for Reduction of Events During extended Observation), a 1-year treatment follow-up to the clopidogrel arms of the CLASSICS trial (Clopidogrel Aspirin Stent International Cooperative Study). Planned trials with clopidogrel in neurology include SPS3 (Secondary Prevention of Small Subcortical Strokes, in patients with symptomatic lacunar stroke), and MATCH (Management of Atherothrombosis with Clopidogrel in High-risk patients, in patients with stroke or transient ischaemic attack plus one additional risk factor), which will compare the efficacy of clopidogrel plus aspirin versus clopidogrel in reducing important ischaemic events. Combination therapy with an oral glycoprotein (GP) IIb/IIIa receptor antagonist plus aspirin has so far been less promising. Trials of three compounds--orbofiban, xemilofiban and sibrafiban--in combination with aspirin for secondary prevention in cardiac patients have reported increased mortality compared with aspirin alone. A similar effect was seen when sibrafiban monotherapy was compared directly with aspirin alone. Trials of newer oral GP IIb/IIIa inhibitors are under way or are planned. The combination of dipyridamole plus aspirin appears to be superior to aspirin alone for the prevention of stroke in patients with stroke or transient ischaemic attack; the effectiveness of this combination is being further investigated in ESPRIT (European/Australian Stroke Prevention in Reversible Ischaemia Trial).     

Low-Molecular-Weight Heparin or Dual Antiplatelet Therapy Is More Effective Than Aspirin Alone in Preventing Early Neurological Deterioration and Improving the 6-Month Outcome in Ischemic Stroke Patients

Background and Purpose

Dual antiplatelet therapy (DAT) with clopidogrel and aspirin has been shown to confer greater protection against early neurological deterioration (END) and early recurrent ischemic stroke (ERIS) than aspirin alone in patients who have experienced an acute ischemic stroke. However, few studies have compared the effects of anticoagulation therapy with low-molecular-weight heparin (LMWH), DAT, and aspirin.

Methods

Patients with acute ischemic stroke (n=1,467) were randomized to therapy groups receiving aspirin (200 mg daily for 14 days, followed by 100 mg daily for 6 months), DAT (200 mg of aspirin and 75 mg of clopidogrel daily for 14 days, then 100 mg of aspirin daily for 6 months), or LMWH (4,000 antifactor Xa IU of enoxaparin in 0.4 mL subcutaneously twice daily for 14 days, followed by 100 mg of aspirin daily for 6 months). The effects of these treatment strategies on the incidence of END, ERIS, and deep-vein thrombosis (DVT) were observed for 10-14 days after treatment, and their impacts on a good outcome were evaluated at 6 months.

Results

The DAT and LMWH were associated with a more significant reduction of END and ERIS within 14 days compared with aspirin-alone therapy. In addition, LMWH was associated with a significantly lower incidence of DVT within 14 days. At 6 months, DAT or LMWH improved the outcome among patients aged >70 years and those with symptomatic stenosis in the posterior circulation or basilar artery compared with aspirin.

Conclusions

LMWH or DAT may be more effective than aspirin alone for reducing the incidence of END and ERIS within 14 days, and is associated with improved outcomes in elderly patients and those with stenosis in the posterior circulation or basilar artery at 6 months poststroke.     

Results of the management of atherothrombosis with clopidogrel in high-risk patients trial: implications for the neurologist

The secondary prevention of ischemic stroke is aided by the use of antiplatelet therapy, and the predominant current choices are aspirin, aspirin plus extended-release dipyridamole, and clopidogrel. The potential utility of combining platelet antiaggregants with different mechanisms of action proved successful with aspirin plus extended-release dipyridamole, and this approach has been explored with the combination of clopidogrel and aspirin. In the Management of Atherothrombosis With Clopidogrel in High-Risk Patients trial, this combination was compared with clopidogrel alone for secondary prevention in patients with transient ischemic attack and stroke in a high-risk population with a high prevalence of other vascular risk factors. A nonsignificant trend for a reduction of the combined endpoint of ischemic stroke, myocardial infarction, vascular death, and rehospitalization was observed in the combination therapy group (P = .24). The frequency of serious, life-threatening bleeding adverse effects was almost doubled in the combination arm. Neurologists need to be aware of these results and avoid the use of clopidogrel plus aspirin in patients with stroke or transient ischemic attack until evidence that the combination is safe in this population is provided. Neurologists faced with patients who have had a stroke or transient ischemic attack and are receiving this combination of antiplatelet agents after coronary stenting should inform their cardiology colleagues of the reported bleeding risk, and they should encourage the use of the combination for as short a time period as possible after such coronary intervention.     

氯吡格雷在非心源性缺血性卒中二级预防中的疗效观察

目的 观察氯吡格雷和阿司匹林肠溶片在非心源性缺血性卒中二级预防中的疗效和安全性。方法 连续收集非心源性缺血性卒中患者并随机分为氯吡格雷组和阿司匹林组,每组55例患者,两组均给予卒中基础治疗。氯吡格雷组加用硫酸氢氯吡格雷口服,50 mg/d。阿司匹林组加用阿司匹林肠溶片口服,75 mg/d。随访1年内两组缺血性卒中复发率和药物不良反应发生率。结果 阿司匹林组卒中复发率为13.5%,而氯吡格雷组复发率为1.8%,差异有统计学意义（P =0.04）;阿司匹林组不良反应发生率为36.4%,氯吡格雷组不良反应发生率为5.5%,差异有统计学意义（P =0.001）。结论 氯吡格雷在非心源性缺血性卒中二级预防中的疗效优于阿司匹林,安全性较高。     

Role of antiplatelet drugs in the prevention of cardiovascular events

Antiplatelet drugs have an established place in the prevention of vascular events in a variety of clinical conditions, such as myocardial infarction, stroke and cardiovascular death. Both European and American guidelines recommend the use of antiplatelet drugs in patients with established coronary heart disease and other atherosclerotic disease. In high-risk patients, such as those with post-acute myocardial infarction (AMI), ischaemic stroke or transient ischaemic attack, and in patients with stable or unstable angina, peripheral arterial occlusive disease or atrial fibrillation, antiplatelet treatment may reduce the risk of a serious cardiovascular event by approximately 25%, including reduction of non-fatal myocardial infarction by 1/6, non-fatal stroke by 1/4 and cardiovascular death by 1/6. Some data indicate that antiplatelet drugs may also have a role in primary prevention. In people who are aged over 65 years, or have hypertension, hypercholesterolaemia, diabetes, obesity or familial history of myocardial infarction at young age, aspirin may reduce both cardiovascular deaths and total cardiovascular events. Aspirin has been studied and used most extensively. It may exert its beneficial effect not only by acting on platelets, but also by other mechanisms, such as preventing thromboxane A₂ (TXA₂)-induced vasoconstriction or reducing inflammation. Indeed, experimental data show that low-dose aspirin may suppress vascular inflammation and thereby increase the stability of atherosclerotic plaque. Moreover, in human studies, aspirin seems to be most effective in those with elevated C-reactive protein levels. Vascular events, however, do occur despite aspirin administration. This may be due to platelet activation by pathways not blocked by aspirin, intake of drugs that interfere with aspirin effect or aspirin resistance. In the CAPRIE (Clopidogrel vs. Aspirin in Patients at Risk of Ischaemic Events) study, long-term clopidogrel administered to patients with atherosclerotic vascular disease was more effective than aspirin in reducing the combined risk of ischaemic stroke, myocardial infarction or vascular death. In the setting of coronary stenting, a double regimen including aspirin and ticlopidine or clopidogrel has proved more effective in the prevention of in-stent thrombosis than aspirin alone. Chronic oral administration of the inhibitors of platelet membrane receptor GP IIb/IIIa has been largely disappointing.     

小剂量替罗非班与双抗治疗进展性脑卒中的疗效对比及安全性评价

目的对比替罗非班和双抗治疗进展性脑卒中的疗效,并评价其临床安全性。方法选取2015-07—2016-10我院神经内科确诊的60例急性进展性脑梗死患者,且1周内病情进展,神经功能缺损较前加重。其中28例采用小剂量替罗非班治疗后接受双抗治疗为实验组,32例仅接受双抗治疗为对照组。治疗3d、7d后,比较2组NIHSS评分、BI指数、血小板计数、各项出凝血指标及出血等并发症。结果治疗3d后2组NIHSS评分差异有统计学意义(P0.05),BI指数差异无统计学意义(P0.05);治疗7d后2组间NIHSS评分及BI指数差异有统计学意义(P0.05)。结论替罗非班治疗进展性脑卒中的疗效显著,安全性良好,可提高患者预后质量。     

强化抗血小板治疗在缺血性脑卒中复发高危患者二级预防中的临床研究

目的观察强化抗血小板药物氯吡格雷在缺血性脑卒中复发高危患者二级预防中的长期疗效及安全性。方法采用艾森卒中风险评分（ESRS）量表筛选住院的急性非心源性缺血性脑卒中复发高危患者100例,随机分为氯吡格雷组和阿司匹林组,每组50例。两组均给予脑卒中常规治疗,氯吡格雷组予氯吡格雷75mg及阿司匹林100mg口服,1周后仅予氯吡格雷75mg,口服。阿司匹林组予阿司匹林200mg,口服,1周后改为100mg,口服。随访3个月和1年,观察两组缺血性脑卒中复发率及药物不良反应发生率。结果随访3个月时,脑卒中复发率：阿司匹林组为6．3％,氯吡格雷组为2．0％,差异无统计学意义（P〉0．05）;药物不良反应发生率：阿司匹林组为14％,氯吡格雷组为2％,差异有统计学意义（P〈0．05）。随访1年时,脑卒中复发率：阿司匹林组为13％,氯吡格雷组为2％,差异有统计学意义（P〈0．05）;药物不良反应发生率：阿司匹林组为38％,氯吡格雷组为6％,差异有统计学意义（P〈0．01）。结论缺血性脑卒中复发高危患者二级预防中强化抗血小板治疗可降低脑卒中复发风险,长期应用获益较高,安全性好。     

用血栓弹力图评价阿司匹林及氯吡格雷在缺血性卒中患者中血小板抑制效应的研究

目的用血栓弹力图评价缺血性卒中患者正规使用阿司匹林及氯吡格雷后血小板抑制率的变化。方法血栓弹力图检测我院123例住院患者抗血小板药物治疗后花生四烯酸(AA)通路和ADP受体途径诱导的血小板抑制率,患者抗血小板药物治疗包括阿司匹林组(n=7)、氯吡格雷组(n=8)、阿司匹林+氯吡格联合组(n=108)。结果 123例患者中,阿司匹林组AA诱导的血小板抑率为(87.04±22.71)%,氯吡格雷组ADP诱导的血小板抑制率平均值为(46.61±24.43)%,阿司匹林+氯吡格雷组AA和ADP诱导的血小板抑制率为分别(77.87±27.98)%和(50.23±29.27)%。服用阿司匹林和氯吡格雷的患者分别有115和116例,其AA和ADP途径血小板抑制率分别为(78.42±27.69)%;(49.99±28.88)%,差异具有显著统计学意义(P=0.000)。其中对阿司匹林和氯吡格雷敏感者(血小板抑制率≥50%)分别为97例(84.34%)和89例(75.72%),而不敏感者(血小板抑制率<50%)分别为18例(15.65%)和27例(23.28%),两种药物疗效间差异无显著统计学意义(χ2=3.706,P=0.054)。结论服用100mg/d阿司匹林,在绝大多数缺血性脑血管病患者中能产生较强的血小板抑制效应,而服用75mg/d氯吡格雷对血小板抑制稍弱,但多数患者仍能达有效的血小板抑制作用。     

How to optimise clopidogrel therapy? Reducing the low-response incidence by aggregometry-guided therapy modification

The inhibitory platelet effect of clopidogrel is insufficient in approximately 5 to 30% of patients. These low responders (LR) face a significantly higher risk of cardiovascular complications. The therapeutic management of LR is still undefined. In the present study, we evaluate a novel therapeutic algorithm to reduce the incidence of clopidogrel resistance. One hundred sixty-one patients on 100 mg of aspirin co-medication underwent elective coronary stenting and were given an initial dosage of 600 mg clopidogrel, followed by 75 mg clopidogrel daily. 48 h later, the platelet responsiveness was tested with ADP (5-20 microM) stimulation by impedance aggregometry (Chronolog 590). A significant rise in impedance (>5 Omega after 6 minutes, aggregation index >65%) was defined as LR. In this subgroup, platelets were stimulated with the selective P2Y(12)-ADP receptor antagonist 2-MeS-AMP. One hundred twenty-three patients were clopidogrel-responders (76.4%) and 38 patients were LR (23.6%). A defect of the ADP-receptor P2Y(12) was found in three out of 38 LR (7.9%). Inhibition of platelet aggregation indicating clopidogrel-responsiveness was achieved with either a clopidogrel high-dose regimen (22/38, 57.9%); a repeat loading dose, doubling the maintenance dose) or with an alternative therapy with ticlopidine (8/38 (21.1%); 250 mg twice daily). Thus the incidence of LR was reduced from 23.6% to 5.0%. Our aggregometer-guided therapeutic algorithm reduced the relative percentage of clopidogrel LR by 78.9%. This approach could prove to be helpful in achieving a further decrease in the incidence of clopidogrel resistance.     

The United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: final results.

From 1979-85, 2435 patients with a transient ischaemic attack or minor ischaemic stroke were randomly allocated to receive long term "blind" treatment with aspirin 600 mg twice daily (n = 815), aspirin 300 mg once daily (n = 806) or placebo (n = 814). No patient was lost to follow up. The "intention to treat" comparison included all the serious vascular events and deaths which occurred before the end of the follow up period on 30 September 1986. There was no difference in efficacy between the 300 mg and 1200 mg daily doses of aspirin, but the lower dose was undoubtedly less gastrotoxic. Also, there was no definite difference in the response of males and females to aspirin. The odds of suffering a major stroke, myocardial infarction or vascular death were 15% less in the combined aspirin groups compared with the placebo group (95% confidence interval 29% reduction to 3% increase in odds) which is compatible with the continuing overview of all the similar trials of antiplatelet drugs where the relative reduction in odds was 25%. There was no statistically significant reduction in the likelihood of either disabling major stroke and vascular death or vascular death occurring.     

Genetic polymorphisms of the platelet receptors P2Y(12), P2Y(1) and GP IIIa and response to aspirin and clopidogrel

INTRODUCTION: There is wide variability in the responses of individual patients to aspirin and clopidogrel. Polymorphisms of several platelet receptors have been related to increased platelet aggregation. We therefore aimed to evaluate whether these polymorphisms are related to altered response to aspirin or clopidogrel. MATERIALS AND METHODS: Patients (n=120) undergoing percutaneous coronary intervention who received aspirin for > or =1 week but not clopidogrel were included. Blood samples were drawn at baseline and 20-24h after a 300-mg clopidogrel dose. Aspirin insensitivity was defined as 5 microM ADP-induced aggregation > or =70% and 0.5 mg/mL arachidonic acid-induced aggregation > or =20%. Clopidogrel insensitivity was defined as baseline minus post-treatment aggregation < or =10% in response to 5 and 20 microM ADP. PlA polymorphism of glycoprotein IIIa, T744C polymorphism of the P2Y(12) gene and the 1622A>G polymorphism of the P2Y(1) gene were genotyped by polymerase chain reaction. RESULTS: There were no differences in polymorphism frequencies between drug-insensitive vs. drug-sensitive patients. There were also no significant differences in response to aspirin (assessed by arachidonic acid-induced aggregation) or to clopidogrel (assessed by ADP-induced aggregation or activation markers) when patients were grouped according to genotype. The only trend observed was lower reduction in PAC-1 binding following clopidogrel in PlA(2) carriers (P=0.065). CONCLUSIONS: We did not find an association between polymorphisms in the platelet receptors GP IIIa, P2Y(12) or P2Y(1) and response to aspirin or clopidogrel in cardiac patients. These findings suggest that the variability in response to anti-platelet drugs is multi-factorial and is not caused only by single gene mutations.     

Comparison of turbidimetric aggregation and in vitro bleeding time (PFA-100) for monitoring the platelet inhibitory profile of antiplatelet agents in patients undergoing stent implantation

The present study compared classical ADP-induced platelet aggregation vs. PFA-100 closure times using collagen/ADP membrane cartridges to monitor the degree of platelet-inhibiting effect of three drug regimens: ticlopidin, abciximab/ticlopidin and loading dose clopidogrel, each on top of aspirin (acetylsalicylic acid, ASA) during and after elective stent placement (intervention) in a total of 31 patients with acute coronary syndrome. Ticlopidin was started directly after stent implantation, abciximab was started before coronary intervention and given intravenously for 12 h, and a clopidogrel loading dose was given before intervention. The 10 patients treated with ticlopidin (500 mg daily) showed no significant prolongation of PFA closure times and a slight increase of ADP-induced platelet aggregation shortly after intervention. In 11 patients treated with abciximab/ticlopidin, the PFA closure times were significantly prolonged, and ADP-induced platelet aggregation was reduced by more than 80% during the 12-h abciximab infusion after intervention. The 10 patients pretreated with loading dose clopidogrel (450 mg followed by 75 mg daily) showed an intermediate but significant prolongation of PFA closure times and reduction of ADP-induced platelet aggregation at levels between the ticlopidin/aspirin- and the abciximab/ticlopidin/aspirin-treated groups. At 20 h after intervention, a similar degree of PFA closure time prolongation and inhibition of ADP-induced aggregation was observed in the abciximab/ticlopidin/aspirin- and the clopidogrel/aspirin-treated patient groups. Both measurement of PFA-100 closure times and inhibition of ADP-induced platelet aggregation showed a similar degree of platelet inhibition, but had rather broad SD ranges, which limit their precision for the follow-up of individual patients. In conclusion, abciximab on top of ticlopidin/aspirin showed a stronger antiplatelet effect for only less than 20 h, as compared to loading dose clopidogrel/aspirin in acute coronary syndrome patients undergoing stent implantation. Whether such a short-term superiority of abciximab, as compared to loading dose clopidogrel, translates into an overall clinical benefit of thombotic and bleeding complications remains to be established in a randomized clinical trial.     

基于高分辨率磁共振成像的氯吡格雷和阿司匹林治疗症状性颅内动脉狭窄患者1年的疗效观察

目的 通过高分辨率磁共振成像观察硫酸氢氯吡格雷片和阿司匹林肠溶片治疗症状性颅内动脉狭窄（intracranial artery stenosis,IAS）的有效性及安全性,旨在为症状性IAS患者的药物治疗选择提供可靠依据。