Mesalazine for the treatment of inflammatory bowel disease

Clopidogrel has become a mainstay in the management of acute coronary syndrome patients over the past decade, as well as an essential component of percutaneous coronary intervention (PCI) pharmacotherapy. Until recently, no prospective study has evaluated the effectiveness of clopidogrel in the setting of an ST-segment elevation myocardial infarction (STEMI). The majority of patients presenting with STEMI receive thrombolytic therapy (aspirin, heparin and a fibrinolytic agent) although many do not achieve or maintain adequate reperfusion of the infarct-related artery. The CLARITY (Clopidogrel as Adjunctive Reperfusion Therapy) study and the PCI–CLARITY substudy were designed to address whether a beneficial effect of clopidogrel, including a loading dose, would be attained among STEMI patients who were being treated with thrombolytic therapy and undergoing coronary angiography during the index hospitalisation. A total of 3491 patients who presented within 12 h after the onset of STEMI were randomly assigned to receive clopidogrel (300-mg loading dose followed by 75 mg daily) or placebo. Patients were scheduled to undergo coronary angiography after 48 h, and those who underwent PCI during the index hospitalisation formed the basis of PCI–CLARITY. This PCI cohort was followed for the combined end point of cardiovascular death, recurrent myocardial infarction and stroke for 30 days.     

Clopidogrel in ST-elevation myocardial infarction patients undergoing percutaneous coronary intervention

Clopidogrel has become a mainstay in the management of acute coronary syndrome patients over the past decade, as well as an essential component of percutaneous coronary intervention (PCI) pharmacotherapy. Until recently, no prospective study has evaluated the effectiveness of clopidogrel in the setting of an ST-segment elevation myocardial infarction (STEMI). The majority of patients presenting with STEMI receive thrombolytic therapy (aspirin, heparin and a fibrinolytic agent) although many do not achieve or maintain adequate reperfusion of the infarct-related artery. The CLARITY (Clopidogrel as Adjunctive Reperfusion Therapy) study and the PCI-CLARITY substudy were designed to address whether a beneficial effect of clopidogrel, including a loading dose, would be attained among STEMI patients who were being treated with thrombolytic therapy and undergoing coronary angiography during the index hospitalisation. A total of 3491 patients who presented within 12 h after the onset of STEMI were randomly assigned to receive clopidogrel (300-mg loading dose followed by 75 mg daily) or placebo. Patients were scheduled to undergo coronary angiography after 48 h, and those who underwent PCI during the index hospitalisation formed the basis of PCI-CLARITY. This PCI cohort was followed for the combined end point of cardiovascular death, recurrent myocardial infarction and stroke for 30 days.     

Expression of Platelet Surface Receptors and Early Changes in Platelet Function in Patients with STEMI Treated with Abciximab and Clopidogrel versus Clopidogrel Alone

BACKGROUND: Platelets play a crucial role in the pathogenesis of acute coronary syndromes (ACS). The efficacy of antiplatelet treatment is pivotal in the success of percutaneous coronary intervention (PCI) performed in patients with ACS. OBJECTIVE: The aim of the study was to investigate the effects of clopidogrel with or without abciximab on the expression of platelet surface receptors and platelet function in patients with ST-segment elevation myocardial infarction (STEMI) undergoing PCI. MATERIALS AND METHODS: Thirty patients with STEMI were included in the study. During acute primary coronary intervention, patients received aspirin (acetylsalicylic acid) and clopidogrel in a loading dose of 300mg. Clopidogrel was the only antiplatelet therapy used by nine patients (group B). Twenty-one patients (group A) received additional abciximab. Blood samples were collected and analyzed twice: before and up to 22 hours after administration of antiplatelet therapy. The platelet aggregation was established as primary platelet-related hemostasis (closure time [CT] assessed using the PFA100 system). The absolute number of platelet surface antigens as CD41a, CD42a, CD42b, CD61, and CD62P were determined by flow cytometry analysis. RESULTS: The study revealed a statistically significant increase in CT induced by adenosine diphosphate and adrenaline (epinephrine) +130 seconds (p < 0.0001) and +94 seconds (p < 0.0001), respectively, in group A patients post-therapy. While in group B the parameters of CT did not change after treatment. In addition, the absolute number of CD41a antigens (glycoprotein [GP] IIb/IIIa) increased significantly after treatment in group A. No significant changes were observed after treatment in the expression of CD62P (P-selectin) antigens in either treatment group. There was a significant reduction in the percentage of CD62P-positive platelets in group B after antiplatelet therapy. CONCLUSIONS: The absolute number of GP IIb/IIIa receptors increases and platelets are not activated up to 12 hours after cessation of abciximab therapy. Treatment of STEMI patients undergoing PCI with a loading dose of clopidogrel reduces the percentage of active platelets but does not influence the CT.     

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

Clopidogrel (Plavix), Iscover) selectively and irreversibly inhibits adenosine diphosphate (ADP)-induced platelet aggregation. Long-term administration of clopidogrel was associated with a modest but statistically significant advantage over aspirin in reducing adverse cardiovascular outcomes in patients with established cardiovascular disease in the CAPRIE trial. In other large well designed multicentre trials, such as CURE, COMMIT and CLARITY-TIMI 28, the addition of clopidogrel to aspirin therapy improved outcomes in patients with acute coronary syndromes. However, some issues regarding the use of clopidogrel remain unresolved, such as the optimal loading dose in patients undergoing percutaneous coronary interventions (PCI) and the optimal treatment duration following drug-eluting intracoronary stent placement. Results of several large randomised trials, therefore, have established clopidogrel as an effective and well tolerated antiplatelet agent for the secondary prevention of ischaemic events in patients with various cardiovascular conditions, including those with ischaemic stroke or acute coronary syndromes. In addition, treatment guidelines from the US and Europe acknowledge the importance of clopidogrel in contemporary cardiovascular medicine.     

Oral antiplatelet therapy and percutaneous coronary intervention

The benefit of oral antiplatelet therapy following percutaneous coronary intervention (PCI) with intracoronary stent implantation is well established. Combined aspirin with clopidogrel or ticlopidine therapy is superior to aspirin alone in reducing thrombotic events after stent placement. Clopidogrel is the drug of choice, given that its efficacy is comparable to ticlopidine and it has a superior safety profile. Despite dual antiplatelet therapy, patients remain at risk of recurrent vascular events. Optimal timing, duration and dosage of antiplatelet therapy remain controversial. Recent evidence suggests additional benefit with clopidogrel pretreatment, high clopidogrel loading dose and long-term dual antiplatelet therapy post-PCI in high-risk patients.     

国产与进口氯吡格雷在冠状动脉介入治疗中的疗效对比分析

目的:对比观察国产氯吡格雷(泰嘉)和进口氯吡格雷(波立维)对经皮冠状动脉介入治疗(PCI)术后的疗效及安全性。方法:将1 258例冠心病患者分为两组,其中国产氯吡格雷组563例,进口氯吡格雷组695例。两组患者术前1 d分别服用泰嘉或波立维300 mg,阿司匹林300 mg作为负荷量,以后泰嘉或波立维75 mg.d-1及阿司匹林100 mg.d-1两联抗血小板治疗,比较泰嘉和波立维对冠心病患者PCI术后9个月的MACE事件、血小板聚集率的影响,以及两药在PCI术后抗血小板作用的安全性。结果:国产和进口氯吡格雷组的血小板聚集率及冠心病患者PCI术后MACE事件差异无统计学意义。结论:国产和进口氯吡格雷均有良好的抗血小板作用,临床疗效相似,不良反应轻微。     

Clopidogrel

Dual antiplatelet therapy with acetylsalicylic acid (aspirin) and clopidogrel is a guideline-recommended standard of care for patients with acute coronary syndromes (ACS) and those who undergo percutaneous coronary intervention (PCI). Despite a large body of clinical evidence obtained from randomized clinical trials and patient registries supporting the efficacy and safety of aspirin plus clopidogrel therapy in these patients, questions concerning the optimal use of dual antiplatelet therapy remain. Widely debated topics pertaining to dual antiplatelet therapy in patients with ACS or undergoing PCI include (i) the appropriate clopidogrel loading dose; (ii) the optimal time to initiate the clopidogrel loading dose; (iii) the optimal duration of dual antiplatelet therapy following ACS or PCI; (iv) impact of variability of platelet response on patient outcomes; and (v) the role of other recommended and emerging P2Y₁₂ antagonists. This review discusses these ongoing controversies regarding the optimal use of dual antiplatelet therapy with aspirin and clopidogrel in patients with ACS or those undergoing PCI.     

替格瑞洛对急性冠脉综合征经皮冠状动脉介入治疗围术期血小板聚集率的影响

目的 探讨替格瑞洛对急性冠脉综合征(ACS)经皮冠状动脉介入治疗(PCI)围术期血小板聚集率(MPAR)的影响.方法 80例确诊为ACS行PCI术患者为研究对象,术前采用随机数字表法分为替格瑞洛治疗组(观察组)和氯吡格雷治疗组(对照组),每组40例.所有研究对象入院前已连续服用氯吡格雷(泰嘉) 75 mg·d-1持续7 d以上者维持原剂量,未曾服用过氯吡格雷者予以300 mg负荷剂量后75 mg·d-1维持.观察组入院前已连续服用替格瑞洛每次90 mg,2次/天,持续7 d以上者维持原剂量,未曾服用过替格瑞洛者予以180 mg负荷剂量后改标准剂量替格瑞洛(每次90 mg,2次/天)治疗.分别于治疗前、术后5 d抽取空腹外周血标本进行MPAR的测定.结果 治疗前观察组和对照组患者MPAR比较,差异无统计学意义 (P>0.05);术后5 d外周血MPAR均明显低于治疗前(P<0.05);观察组MPAR明显低于对照组(P<0.05).结论 替格瑞洛较氯吡格雷能更好地抑制ACS血管病变患者PCI围术期MPAR,降低早中期不良心血管事件的发生率,对重度冠状动脉血管病变的患者具有更好抗血小板聚集的治疗效果.     

冠脉介入治疗围手术期使用氯吡格雷的循证医学证据

目的总结氯吡格雷在冠脉介入治疗（PCI）患者中应用的循证医学证据。方法检索Pubmed、Cochrane Library、CNKI、中文科技期刊数据库、万方数据库从建库至2014年2月的有关文献,根据纳入相关标准进行文献收集,然后对其作用机制、有效性系统评价文献汇总分析。结果共纳入33篇meta分析文献,证实氯吡格雷在PCI患者中抗血小板治疗的有效性,认为其高剂量维持和高剂量负荷并采取预治疗的策略似乎更有益。结论氯吡格雷是临床应用广泛的抗血小板药物,虽存在一定的局限,但其与阿司匹林联用,目前在PCI患者中发挥着积极的作用。     

Triple antiplatelet therapy in acute coronary syndromes

Heightened platelet activity plays a critical role in thrombus formation, which is central to acute coronary syndromes (ACS), including non-ST-segment elevation (NSTE)-ACS (comprising unstable angina pectoris and non-ST-segment elevation myocardial infarction [NSTEMI]) and ST-segment elevation myocardial infarction (STEMI), and has been implicated in poor clinical outcome. Platelets not only impact coronary thrombus but are major contributors to microcirculatory dysfunction and vascular inflammation. Efforts to inhibit platelet function, including antiplatelet therapy, are paramount to the management of ACS; thus, a growing recognition of the various pathways driving platelet activity has given rise to the need for multiple agents that impart complimentary mechanisms of action. While only inhibiting platelet activation will still allow for aggregation, i.e. the binding of glycoprotein (GP) IIb/IIIa receptors to fibrinogen, solely blocking aggregation may leave platelet-activating pathways free to sustain the production and release of various pro-inflammatory and pro-thrombotic compounds. The benefit of 'triple antiplatelet therapy', referring to the combination of aspirin, a thienopyridine or non-thienopyridine adenosine diphosphate (ADP)/P2Y12 receptor blocker and a GPIIb/IIIa inhibitor (GPI), has been demonstrated in patients with NSTE-ACS who ultimately undergo percutaneous coronary intervention (PCI) and are determined to be at an elevated risk for ischaemic events, and in patients undergoing primary PCI. It is therefore recommended by the European Society of Cardiology (ESC) and American College of Cardiology/American Heart Association. Furthermore, the rationale for adding a GPI, particularly in patients with STEMI, is backed by studies that have shown negligible effects of a 600?mg clopidogrel loading dose, despite being administered 4 hours prior to PCI. Moreover, it has been observed that the physiological state of STEMI may deem dual antiplatelet therapy ineffective, because during an acute event the absorption of clopidogrel may be impaired. Nonetheless, there is still considerable variability with respect to the use of triple antiplatelet therapy such as that documented in the Euro Heart Survey. The perception that the mortality benefit afforded by adding a GPI to dual oral antiplatelet therapy does not outweigh the risk is a likely factor. This may be fuelled by results of trials such as BRAVE-3, which, inconsistent with those for On-TIME 2, failed to prove the value of adding a GPI to dual oral antiplatelet therapy in patients with STEMI. Subsequent analyses have indeed demonstrated the positive benefit-risk ratio associated with adding a GPI and determined that the timing of GPI administration could have an impact on clinical outcome related to its impact on infarct size in patients with STEMI. Additionally, it has been presumed that a synergistic effect exists between P2Y12 inhibitors and GPIs. Triple antiplatelet therapy has a significant role to play in the management of patients with ACS managed with PCI. An understanding of patient risk status and timing of symptoms and bleeding risk is crucial to patient selection and ensuring that this therapy is optimized. Though no interaction has been noted in trials of newer, more potent antiplatelet agents, future studies are key to determining the role of this strategy in the era of these more potent agents.     

The impact of genetic polymorphisms of P2Y12, CYP3A5 and CYP2C19 on clopidogrel response variability in Iranian patients

Clopidogrel is an inhibitor of platelet ADP P2Y12 receptors and currently used for prevention of stent thrombosis. Despite certain clinical benefit using this drug in patients undergoing percutaneous coronary intervention (PCI), some patients do not attain adequate antiplatelet effects. In this study, we investigated the role of three genetic factors (P2Y12, CYP3A5, CYP2C19), demographic characteristics, and pathologic condition on clopidogrel response variability in Iranian patients after PCI. Patients who were candidate for elective PCI were enrolled in this study. All patients had received aspirin 80-325 mg daily for ≥ 1 week before PCI. Blood samples were taken from patients at baseline, 2 h after taking a 600-mg loading dose of clopidogrel, 24h and 30 days after PCI. Platelet aggregation was measured by turbidimetric aggregation assay with two different concentrations of ADP (5 and 20 μM). CYP2C19*2(rs4244285), CYP2C19*3(rs4986893), CYP3A5 (A6986G), and P2Y12 (T744C) genotypings were performed by PCR-RFLP. One hundred and twelve patients were included in this study. Maximum clopidogrel non-responsiveness (25.90%) occurred at 2 h after taking 600 mg of the loading dose of clopidogrel. Although there were no significant associations between clopidogrel responsiveness and polymorphisms of CYP2C19, CYP3A5, and P2Y12 (P > 0.05), subjects who were CYP3A5 genotype expressor had a greater inhibition of platelet aggregation. No significant associations were observed between environmental factors and clopidogrel responsiveness (P > 0.05). Our results showed that P2Y12, CYP3A5, and CYP2C19 polymorphisms along with non-genetic factors were not responsible for the interindividual variability in response to clopidogrel in Iranian population.     

Review of clopidogrel dose escalation in the current era of potent P2Y12 inhibitors

Dual anti-platelet therapy with aspirin and a P2Y12 inhibitor is the standard of care for patients with acute coronary syndromes (ACS) and for patients undergoing percutaneous coronary intervention (PCI). Clopidogrel is associated with increased risk of high on-treatment platelet reactivity (HTPR) compared to ticagrelor and prasugrel. Investigators have therefore sought to “escalate” clopidogrel dosing to overcome HTPR to reduce ischemic/thrombotic events. In this review, we will summarize the evidence for dose escalation in the context of genetic determinants of resistance and platelet function data. We will review contemporary clinical trials that have sought to improve delivery of dual antiplatelet therapy to patients with coronary artery disease and discuss the potential of clopidogrel dose escalation in specific populations.     

Aspirin and Platelet Adenosine Diphosphate Receptor Antagonists in Acute Coronary Syndromes and Percutaneous Coronary Intervention

Platelet activation and aggregation are key components in the cascade of events causing thrombosis following plaque rupture. Antiplatelet therapy is essential in the treatment of patients with acute coronary syndromes (ACS) and for those requiring percutaneous coronary intervention (PCI). Aspirin (acetylsalicylic acid) is a well established antiplatelet therapy and is mandated for secondary prevention of cardiovascular events following ACS. In patients with ACS, the addition of clopidogrel to aspirin is more effective than aspirin alone. For patients undergoing PCI, dual antiplatelet therapy with aspirin and clopidogrel is warranted. Aspirin should be continued indefinitely after PCI. Pretreatment of patients with clopidogrel prior to PCI lowers the incidence of cardiovascular events, yet the optimum timing of drug administration and dose are still being investigated, as is the duration of therapy following PCI. Late-stent thrombosis with drug-eluting stents has pushed the recommendation for duration of clopidogrel therapy up to 1 year and perhaps beyond, in patients without risks for bleeding. The concepts of aspirin and clopidogrel resistance are important clinical questions. No uniform definition exists for aspirin or clopidogrel resistance. Measurements of resistance are often highly variable and do not necessarily correlate with clinical resistance. Noncompliance remains the most prominent mode of resistance. Screening of selected patient populations for resistance or pharmacologic intervention of those patients termed 'resistant' warrants further study.     

Comparison of bolus only with bolus plus infusion of bivalirudin in patients undergoing elective percutaneous coronary intervention: a retrospective observational study

Background: Anticoagulation therapy during percutaneous coronary intervention (PCI) has been the focus of numerous clinical trials. Low-anticoagulant doses have been successfully used in patients undergoing elective PCI, a situation with low-thrombogenic milieu. Objective: The purpose of the study was to evaluate the safety and efficacy of shorter duration of treatment with bivalirudin in patients undergoing elective PCI and receiving optimal antiplatelet therapy. Methods: We compared patients undergoing PCI who received aspirin and clopidogrel loading dose in addition to either conventional bivalirudin dosing (intravenous [IV] bolus of 0.75 + 1.75 mg/kg per h for the duration of PCI; n = 197) or a reduced bivalirudin dose (IV bolus of 0.75 mg/kg; n = 200). Results: Procedural success was obtained in 100% of cases. The primary end point (in-hospital death, acute myocardial infarction, or need for urgent target vessel revascularization) did not differ between both the groups (6 patients [3%] in the conventional dose group vs 5 patients [2.5%] in the reduced dose group). Major bleeding occurred in 1 patient in the conventional dose group (P = nonsignificant [NS]). Minor bleeding occurred in 4 patients (2%) in the conventional dose group vs 5 patients (2.5%) in the reduced dose group (P = NS) and was mainly due to bleeding at entry site. Conclusion: In patients undergoing elective PCI, using bivalirudin as a bolus only dosing may be as effective and less costly when compared with bolus followed by an infusion for the duration of the intervention. A larger study is needed to confirm our findings.     

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.

     

Facilitated PCI: rationale, current evidence, open questions, and future directions

Both thrombolysis and primary percutaneous coronary intervention (PCI) are validated therapies in the treatment of ST-elevation acute myocardial infarction (STEMI). Primary PCI appears now to be more effective, provided the vessel patency is restored within 120 minutes. An approach combining the possibility of quickly starting a clot-dissolving medication with a subsequent PCI of the culprit lesion has therefore recently gained considerable interest. Facilitated percutaneous coronary intervention (PCI) refers to a pretreatment with any pharmacological agent allowing the achievement of some recanalization and possibly myocardial reperfusion, which might translate into an improved clinical outcome. Many drugs reduce the thrombus burden; however, the term "facilitated" is currently operatively restricted to glycoprotein GP-IIb-IIIa inhibitors, thrombolytic drugs, and their combination. Several earlier clinical trials tested the hypothesis that facilitated PCI in the setting of STEMI allows the achievement of a better myocardial reperfusion compared with primary PCI and that this benefit translates into an improved clinical outcome. However, after the first promising results, the recent ASSENT-4 trial has been prematurely interrupted because of higher in-hospital mortality in the group of patients who underwent full-dose tenecteplase followed by PCI compared with subjects undergoing primary PCI alone. After a critical review of the current knowledge, and pending the completion of ongoing trials, no clear evidence currently exists on the benefit of any systemic pharmacological facilitation of PCI beyond the upfront administration of dual oral antiplatelet therapy with aspirin and clopidogrel. While awaiting the results of a few other currently ongoing trials, facilitated PCI should now probably be restricted to the administration of glycoprotein IIb-IIIa inhibitors for patients at high risk of cardiovascular events and at low risk of bleeding when a more than 60-minute delay to primary PCI is anticipated. In patients having first medical contact within 3 hours, with an anticipated absolute delay to PCI of more than 90 minutes, thrombolysis can be safely recommended.     

Clopidogrel use with stenting

Previous clinical trials have established that clopidogrel is beneficial when used with coronary artery stenting. However, questions remain as to when the clopidogrel treatment should be started and how long treatment should be continued for. In a Clopidogrel Registry, it was shown that when subjects received a loading dose of clopidogrel 300 mg, 6-24 h before the intervention and clopidogrel maintenance for 1 month, the primary end point at 30 days (acute myocardial infarction, all cause death and revascularisation) was lower than in subjects who were just given clopidogrel maintenance. An observational study has shown that there are no additional benefits from continuing to use clopidogrel after 6 months from bare-metal stenting. In contrast, long-term treatment with clopidogrel is beneficial in subjects given drug-eluting stents, when long-term stent thrombosis can be a rare complication. Thus, in subjects given drug-eluting stents, there was an incidence of death and non-fatal myocardial infarction (6-24 months after stenting) of 8.4% without clopidogrel and 2.1% with clopidogrel. These results suggest that clopidogrel pretreatment should be used with stenting, and that with drug-eluting stents, clopidogrel treatment should be continued for at least 24 months.     

Role of Prasugrel, a Novel P2Y12 Receptor Antagonist, in the Management of Acute Coronary Syndromes

Prasugrel is a new P2Y₁₂ receptor antagonist that has been investigated for the treatment of atherothrombosis in patients with cardiovascular disease undergoing percutaneous coronary intervention (PCI). Similar to other thienopyridines, prasugrel is a prodrug that requires biologic conversion to active metabolites. Studies have demonstrated the ability of prasugrel to selectively and irreversibly inhibit ADP-induced platelet aggregation to a greater degree than clopidogrel. In a large randomized, double-blind, double-dummy clinical trial, it was demonstrated that treatment with prasugrel (n=6813; 60mg loading dose followed by 10 mg/day) significantly reduced the incidence of a composite endpoint of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke during the median follow-up of 14.5 months, compared with clopidogrel (n=6795; 300mg loading dose followed by 75 mg/day) in patients with acute coronary syndromes scheduled to undergo PCI. The number of patients who would need to be treated with prasugrel instead of clopidogrel in order to prevent one primary efficacy outcome was 46. Landmark analyses found that prasugrel not only reduced the incidence of individual clinical endpoints and stent thrombosis during the loading dose phase (randomization to 3 days), but also that these benefits continued throughout the maintenance phase (from 3 days until the end of the trial). Nonsurgical-related Thrombolysis In Myocardial Infarction (TIMI)-major and life-threatening bleeds were significantly more frequent in patients receiving prasugrel compared with clopidogrel. Patients with a history of stroke or transient ischemic attack (TIA) seem to be at especially high risk for bleeding, as well as patients aged >75 years and those weighing <60kg. A prespecified analysis of net clinical benefit, which took into account the effects on both the primary efficacy and safety endpoints, was conducted. After taking into account the higher bleeding rates, the net clinical benefit still favored prasugrel use compared with clopidogrel. However, patients with prior stroke or TIA, patients older than 75 years, and patients weighing <60kg did not demonstrate a net clinical benefit with prasugrel use. Prasugrel was approved for use in Europe by the European Commission in February 2009, and is currently available in the UK. In July 2009, the US Food and Drug Administration (FDA) approved the use of prasugrel for the reduction of thrombotic cardiovascular events (including stent thrombosis) in patients with acute coronary syndrome who are to be managed with PCI.     

Prevention of coronary heart disease with aspirin and clopidogrel: efficacy, safety, costs and cost-effectiveness

Atherothrombotic coronary artery disease is the single most common cause of death worldwide and a growing public health problem. Platelets play a central role in the pathogenesis of atherothrombosis and are therefore commonly targeted by one or more antiplatelet drugs as part of primary and secondary atherothrombosis prevention strategies. Aspirin reduces the risk of serious vascular events (myocardial infarction, stroke or cardiovascular death) by approximately 20% in a broad range of high-risk patients and remains the first-line antiplatelet drug because of its relative safety, low cost and cost-effectiveness. Compared with aspirin alone, clopidogrel reduces the risk of serious vascular events by approximately 10% and the combination of aspirin and clopidogrel reduces the risk by approximately 20% in patients with non-ST-segment elevation acute coronary syndrome. Clopidogrel has a similar safety profile to aspirin but clopidogrel tablets are substantially more expensive. However, the incremental cost-effectiveness ratio of clopidogrel compared with aspirin is favourable, particularly in high-risk patients and is intermediate compared with a range of other effective therapeutic strategies for the treatment of coronary heart disease. Clopidogrel should be considered as a replacement for aspirin in patients who are allergic to aspirin, cannot tolerate aspirin, have experienced a recurrent atherothrombotic vascular event whilst taking aspirin and are at very high absolute risk of a serious vascular event (e.g., > 20%/year). The combination of clopidogrel and aspirin should be considered in patients with non-ST-segment elevation acute coronary syndrome or undergoing percutaneous coronary intervention.     

The pattern of platelet response to clopidogrel in Iranian patients after percutaneous coronary intervention

Despite certain clinical benefit in using clopidogrel in patients undergoing percutaneous coronary intervention (PCI), some patients do not attain adequate antiplatelet effects. In this study, the authors investigated the response to clopidogrel in Iranian patients after PCI. Patients who were candidates for elective PCI were enrolled in this study. All patients had received aspirin 80 to 325 mg daily for ≥1 week before PCI. Blood samples were taken from patients at baseline, 2 hours after taking a 600-mg loading dose of clopidogrel, and 24 hours and 30 days after stenting. Platelet aggregation was measured by light transmittance aggregometry with adenosine diphosphate (5 and 20 μM) and arachidonic acid (500 and 5000 μg/mL). One hundred twelve patients were included (79 men, 33 women). Maximal and minimal clopidogrel nonresponsiveness occurred at 2 hours (26%) and 48 hours (13%) after taking 600 mg clopidogrel, respectively. Pretreatment platelet reactivity had no effects on posttreatment platelet reactivity. Moreover, clopidogrel responsiveness did not correlate with pretreatment reactivity. Patients' demographic and procedural characteristics had no significant effect on clopidogrel responsiveness. The frequency of clopidogrel nonresponsiveness in this study was similar to other studies. However, clopidogrel required more than 2 hours for induction of its maximal antiplatelet effect in this study.