Review of pharmacoeconomic evaluation of genotype-guided antiplatelet therapy

Introduction: Clopidogrel is an antiplatelet agent widely prescribed for acute coronary syndrome (ACS), and it is activated by the CYP enzyme system to active metabolite. CYP2C19 loss-of-function (LOF) allele(s) affect the responsiveness of clopidogrel, but not the new antiplatelet agents (prasugrel and ticagrelor). We reviewed the pharmacoeconomic studies on genotype-guided use of new antiplatelet agents.

Areas covered: A literature search was conducted between the period of 2000 and 2014. Seven studies including cost-effectiveness and risk-benefit analyses of CYP2C19 genotype-guided antiplatelet therapy in ACS patients were reviewed. Genotype-guided prasugrel was found to be cost-effective when compared with universal antiplatelet therapy in four studies. Three studies showed genotype-guided ticagrelor to be cost-effective in ACS patients with percutaneous coronary intervention (PCI), and universal ticagrelor to be cost-effective in ACS patients. Drug cost of antiplatelet agents and relative risk of the new antiplatelet versus clopidogrel for clinical events were common influential factors of cost-effectiveness analyses.

Expert opinion: All studies in the present review focused on selecting antiplatelet agents for carriers of CYP2C19 LOF allele(s). Cost-effectiveness of genotype-guided use of antiplatelets was demonstrated in high-risk ACS patients.     

Comparative effectiveness of coronary artery bypass grafting (CABG) surgery and percutaneous coronary intervention (PCI) in elderly patients with diabetes

Objective: To compare the relative effectiveness of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) among elderly patients with diabetes regarding acute myocardial infarction (AMI), stroke, repeat revascularization, and all-cause mortality.

Methods: A retrospective cohort study was conducted using the 2006–2008 5% national sample of Medicare claims data. Elderly (≥65 years) beneficiaries with at least two claims of diabetes separated by ≥30 days and who had at least one inpatient claim for multi-vessel CABG or PCI between 1 July 2006 and 30 June 2008 were identified. The date of beneficiary’s first CABG or PCI was defined as the index date. All patients were followed from the index date to 31 December 2008 for outcomes. CABG and PCI patients were 1:1 matched on propensity scores and index dates. Cox proportional hazards models were used to compare postoperative outcomes between patients undergoing CABG versus PCI.

Results: The matched sample consisted of 4430 patients (2215 in each group). The Cox proportional hazards models showed that, compared to patients undergoing PCI, CABG was associated with a lower risk of postoperative AMI (hazard ratio [HR]: 0.494; 95% CI: 0.396–0.616; p?<?.0001), repeat revascularization (HR: 0.194; 95% CI: 0.149–0.252; p?<?.0001), the composite outcome (HR: 0.523; 95% CI: 0.460–0.595; p?<?.0001), and all-cause mortality (HR: 0.775; 95% CI: 0.658–0.914; p?=?.0024); postoperative risk of stroke was not significantly different between the two groups (HR: 0.965; 95% CI: 0.812–1.148; p?=?.691).

Conclusions: CABG appears to be the preferred revascularization strategy for elderly patients with diabetes and coronary heart disease. However, this result should be interpreted considering study limitations, for example, several patient clinical variables and physician-related factors which may affect procedure outcomes are not available in the data. Clinical decisions should be individualized considering all patient- and physician-related factors.     

Developments in antiplatelet therapy for acute coronary syndromes and considerations for long-term management

ABSTRACT

Objective: This article reviews the currently available antiplatelet therapies and emerging investigational drugs in the treatment of acutecoronary syndrome (ACS), and considerations for primary and secondary prevention in the long-term management of ACS patients undergoing percutaneous coronary intervention (PCI).

Research design and methods: Primary studies and reviews in the peer-reviewed, English-language literature were identified through searches of MEDLINE (1966–2008) using the terms ‘acute coronary syndrome’, ‘antiplatelet’, ‘aspirin’, ‘long-term management’, ‘P2Y₁₂ receptor’, and ‘thienopyridine’. Additional references were obtained by searching the reference lists of the identified articles. Articles were included if they were recently published and pertinent, patient-focused, and authors were recognized as leaders in the field. Current review is limited by literature search on single database.

Results: Platelets play a major role in atherogenesis and the formation of thrombi, the main events in the pathogenesis of ACS. Although aspirin is an effective antiplatelet agent, efficacy and safety data from a number of randomized clinical trials on atherothrombotic disease support the use of dual antiplatelet therapies such as aspirin and thienopyridines over single antiplatelet therapy for ACS and up to 1?year following ACS. Antiplatelet agents reduce, but do not eliminate, ischemic events after ACS due, in part, to variable individual response (or resistance) in antiplatelet agents, non-compliance, progression of atherosclerosis, modest inhibition of platelet aggregation (IPA) levels and other factors. Several antiplatelet agents, including novel P2Y₁₂-receptor antagonists and thrombin-receptor antagonists, are currently under investigation for ACS and primary and secondary prevention in the long-term management of patients undergoing PCI.

Conclusions: Current antiplatelet therapies have clinical benefits such as reducing immediate and long-term cardiovascular risk, but substantial residual risk remains indicating a need for new therapeutic agents. Additional large randomized trials are necessary to determine the most appropriate treatment regimens for ACS patients.     

Effects of tirofiban on acute systemic inflammatory response in elective percutaneous coronary interventions

SUMMARY

Objective: In this study the effect of a specific glycoprotein IIb/IIIa inhibitor, tirofiban [which also has antiplatelet activity on acute systemic inflammatory responses (IR) during elective percutaneous coronary intervention (PCI)] was evaluated.

Patients and methods: Patients with stable angina pectoris and similar baseline characteristics who angiographically had a single lesion in their coronary arteries with a PCI performed on that lesion were enrolled in the study. One group of patients (control group, n?=?52) received 0.9% NaCl (15?mL/h for 24h) and the other group (tirofiban group, n?=?55) had tirofiban (10|ig/kg bolus infusion in 3min and 0.15jj,g/kg/mir for 24h) in addition to stenting without pre-dilatation. The effect of interventional procedure on levels of cardiac troponin T (cTnT) and several parameters of acute IR (leukocytes, fibrinogen, C-reactive protein, interleukin-1, interleukin-6, interleukin-8 and tumor necrotizing factor-α) was assessed on blood samples obtained from all patients before PCI and at pre-specified time points after PCI.

Results: During the follow-up after PCI, the number of patients becoming cTnT-positive (> 0.1?ng/mL) was greater in the control group [12 (23%) patients vs. 3 (5%) patients, p?=?0.01]. However, both groups had changes (generally observed as elevations) in their levels of all inflammatory parameters during the study and C-reactive protein, interleukin-6 and tumor necrotizing factor-α levels were elevated significantly. Yet, no significant difference occurred between groups due to these changes in any phase of the study (p?>?0.05).

Conclusions: Based on the findings of this study, it was concluded that although tirofiban limits development of myocardial necrosis during elective PCI, it does not directly affect the acute systemic inflammatory responses.     

Safety of bivalirudin in patients with coronary artery disease

Introduction: Various limitations of unfractionated heparin (UFH) have triggered a search for new antithrombotic therapies for patients with coronary artery disease (CAD). Bivalirudin is a direct thrombin inhibitor with several pharmacological advantages over UFH and is currently endorsed by practice guidelines, particularly in patients with acute coronary syndromes undergoing percutaneous coronary intervention (PCI). To maximize effectiveness of an antithrombotic regimen and reduce complications, both ischemic and bleeding risks should be known when an antithrombotic strategy is chosen.

Areas covered: This review focuses on the safety and tolerability of bivalirudin in patients with CAD in the setting of currently approved indications. Synthesis of evidence has been made from clinical trials, systematic reviews, meta-analyses and registries (1992 – 2011). The reader is provided with an overview of pharmacological properties of bivalirudin and its efficacy, with special emphasis on its safety in patients with CAD.

Expert opinion: Bivalirudin has an impressive safety profile in CAD patients treated with PCI. Bivalirudin is the antithrombotic of choice in suspected or verified heparin-induced thrombocytopenia. For ST elevation myocardial infarction patients undergoing primary PCI, bivalirudin should become the preferred antithrombotic agent together with early institution of antiplatelet therapy.     

The discovery and development of prasugrel

Introduction: Prasugrel (CS-747, LY640315) is a third-generation thienopyridine, which gained approval by the FDA in 2009 for its use in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

Areas covered: This article focuses on the preclinical profile of prasugrel. Using published preclinical and clinical studies, the authors summarize the pharmacokinetics, pharmacodynamics, and pharmacogenomics of prasugrel and their distinguishing features in efficacy and safety.

Expert opinion: Prasugrel has a more rapid, more potent antiplatelet effect with less interindividual response variability when compared to clopidogrel. Those therapeutic advantages are attributed to features of its chemical structure that favor the metabolic conversion of prasugrel to its active metabolite. However, the increased risk of bleeding has been associated with a greater antiplatelet effect and dosing profile; this is especially the case in those patients who are at a higher risk of bleeding complications. It is therefore important for an optimal dosing strategy of prasugrel to be identified to provide a formulation that has the best balance for efficacy and safety.     

急性冠脉综合征PCI术后患者双联抗血小板治疗相关不良反应特点及危险因素分析

目的 探讨急性冠脉综合征（ACS）患者接受经皮冠状动脉介入治疗（PCI）后服用替格瑞洛和阿司匹林双联抗血小板治疗出现不良反应的特点及危险因素。方法 前瞻性纳入2018年3月—2018年6月郑州市第七人民医院收治的PCI术后服用替格瑞洛和阿司匹林的ACS患者100例,采用VerifyNow-P2Y12系统检测患者血小板反应性并随访6个月,根据是否发生相关不良反应分为对照组和不良反应组,收集对比两组患者临床基线资料,采用单因素和多因素Logistic回归分析出血和呼吸困难的危险因素。结果 纳入研究的患者未出现不良反应的40例纳入对照组,出现不良反应的60例纳入不良反应组,双联抗血小板治疗相关不良反应发生率60.0%,84例（84.0%）患者存在低血小板反应性。两组患者在年龄、性别、合并疾病、血小板反应性等方面差异不具有统计学意义（P＞0.05）,不良反应组吸烟患者占比明显高于对照组（51.7%vs27.5%,P=0.016）。不良反应主要临床表现为皮肤黏膜出血和轻中度呼吸困难,用药后1个月内出血和呼吸困难发生率显著高于用药后2～6个月（出血发生率：38.0%vs1.0%,P＜0.001;呼吸困难发生率：32.0%vs8.0%,P＜0.001）。多因素Logisitc回归分析显示老年、女性和贫血是双联抗血小板治疗相关出血的独立危险因素（P＜0.05）,吸烟和出血事件是双联抗血小板治疗相关呼吸困难的独立危险因素（P＜0.05）。结论 ACS患者PCI术后双联抗血小板治疗早期出血和呼吸困难发生率高但程度较轻,对于合并危险因素的患者应提前评估、加强监测,最大限度地降低药品不良反应的发生。     

PCI术后早期抗血小板药物反应性与西雅图心绞痛量表评分的相关性研究

目的 评估PCI术后早期血栓弹力图（thromboelastography,TEG）测定的阿司匹林和氯吡格雷反应性与西雅图心绞痛量表（SAQ）评分之间的相关性。方法 43例PCI术后患者使用TEG测定出花生四烯酸（AA）和二磷酸腺苷（ADP）的最大血块强度（maximum amplitude,MA）和血小板抑制率（inhibition rate,IR）。阿司匹林反应性根据AA-IR分为低（<50%）,中（50%~85%）,高（>85%）。氯吡格雷反应性根据ADP-MA分为低（>47 mm）,中（31~47 mm）,高（<31 mm）。根据2种药物的反应性组合为联合高反应组、联合中反应组和联合低反应组。患者在PCI术前和术后4周进行SAQ评分。结果 3组患者的性别构成、年龄、植入支架数、高血压和糖尿病患病率的差异均无统计学意义。3组患者术前SAQ评分无显著差异,术后4周SAQ评分均较术前明显提高,但联合低反应组患者的SAQ评分较其他2组相对较低（P<0.05）。术后SAQ评分与抗血小板药物反应性之间存在相关性（Pearson法）。结论 PCI术后早期阿司匹林和氯吡格雷反应性与SAQ评分具有相关性,抗血小板药物低反应可能是患者PCI术后早期再发心绞痛的重要危险因素。     

Developing drugs for use before,during and soon after percutaneous coronary intervention

Introduction: Percutaneous coronary intervention (PCI) is a milestone for treating coronary artery disease (CAD). Antithrombotic therapy is essential to prevent ischemic complications, including the microvascular no-reflow, while minimizing bleeding events.

Areas covered: This overview discusses available and developing drugs for PCI including anticoagulants, antiplatelets and treatment of no-reflow.

Expert opinion: For years unfractionated heparin (UFH) has been the unique anticoagulant to be used before and during PCI. Enoxaparin showed similar efficacy and safety, yet, based on recent trials, bivalirudin has been shown to have some benefits, particularly for patients with ST-segment elevation myocardial infarction (STEMI). The evidence concerning new anticoagulants is still preliminary, except for new oral anticoagulants, particularly rivaroxaban that showed intriguing findings and is currently under investigation. Dual antiplatelet therapy (DAPT) is the standard of care after PCI, but new developments have recently emerged. Indeed, ticagrelor and prasugrel are currently recommended over clopidogrel due to their significant reduction of ischemic events in acute coronary syndrome (ACS) whereas clopidogrel remains the choice in stable CAD. Among new agents, vorapaxar and cangrelor showed positive but limited evidence and might be considered at least in selected patients. Conversely, evidence on effective treatments for no-reflow remains limited and would require future dedicated research.     

急性心肌梗死经皮冠状动脉介入术后支架内血栓形成临床研究

目的探讨急性心肌梗死（AMI）经皮冠状动脉介入治疗（PCI）后支架内血栓形成（ST）的发生率、危险因素、治疗及预后。方法选择AMI行PCI治疗后发生ST的患者28例,围手术期均使用阿司匹林、硫酸氯吡格雷片或噻氯匹定双重标准抗血小板治疗和肝素抗凝治疗。结果因胃溃疡或出血未用或停用抗血小板药物后发生ST8例,在经球囊扩张（PTCA）并尿激酶溶栓术中发生室颤死亡1例,发生ST后急性左心功能衰竭死亡1例。22例均于PTCA或PCI治疗血管再通。2例经冠脉搭桥术（CABG）治疗好转。2例可能的ST在术后24h内出现心绞痛,心电图示ST段抬高,肌钙蛋白升高,经加强抗凝抗血小板治疗后病情好转。多因素logist回归显示前壁心肌梗死、心功能不全、C型病变、支架的长度及早期停用抗血小板药物是发病的危险因子（P〈0.05）。结论 AMI患者PCI术后的ST形成发生率很低,但是预后较差。复杂的冠状动脉病变型类型和抗血小板治疗依从性差可能是ST形成的主要危险因素,积极早期介入治疗可改善预后。     

Antiplatelet therapy in acute coronary syndromes

Introduction: Antiplatelet therapy is the cornerstone of treatment for patients with acute coronary syndromes in the acute phase and in long-term management. Over the last few years, new antiplatelet drugs have been developed and the therapeutic landscape has rapidly evolved.

Areas covered: We review the available evidence and most recent data concerning all of the principal classes of antiplatelet agents, including aspirin, thienopyridines and glycoprotein IIb/IIIa inhibitors, as well the impact of the new drugs prasugrel and ticagrelor and the available data concerning cangrelor, elinogrel and PAR-1 inhibitors (still under development).

Expert opinion: This review considers the management of antiplatelet therapy in the light of recent advances, highlighting how to identify patients who will receive the greatest benefit from the older and newer agents, and underscoring the importance of carefully balancing the risks of ischaemia and bleeding in order to improve clinical outcomes. Finally, the paper discusses the potential role of functional and genetic tests in guiding the choice of antiplatelet therapy in a future perspective of ‘personalised medicine’.     

Genetic and non-genetic factors affecting the response to clopidogrel therapy

Introduction: Clopidogrel (CLP) is a second-generation thienopyridine that prevents platelet aggregation by inhibiting the adenosine diphosphate receptor located on the platelet surface. The use of CLP in combination with aspirin has become standard treatment in patients with acute coronary syndromes and stent implantation. Data suggests that a significant percentage of individuals treated with CLP do not receive the expected therapeutic benefit because of a decreased platelet inhibition. The clinical consequences of an inadequate platelet response are cardiovascular complications, which can lead to acute myocardial infarction, stroke and death. The mechanism underlying CLP resistance is multifactorial and includes genetic polymorphisms and non-genetic causes (such as drug–drug interactions, co-morbidities, age).

Areas covered: This article reviews the so-far accumulated evidence on the role of genetic polymorphisms and non-genetic factors, as determinants of the antiplatelet response to CLP. Pharmacodynamic and clinical aspects of the CLP nonresponsiveness are also presented. Relevant papers were identified by an extensive PubMed search using appropriate keywords.

Expert opinion: Impaired platelet inhibition in CLP poor responders is a real problem, as it leads to serious clinical consequences. Therefore, prediction models that include pharmacogenetic knowledge and non-genetic risk factors of low response to the drug are needed in the individualization of antithrombotic therapy. Alternative antiplatelet strategies that should be considered to overcome this problem include dose modification, adjunctive antiplatelet drug usage, and use of newer agents.     

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.     

Healthcare resource use and cost associated with timing of pharmacological treatment for major depressive disorder in the United States: a real-world study

Abstract

Background: Guidelines recommend selective serotonin reuptake inhibitors (SSRI) and serotonin norepinephrine reuptake inhibitors (SNRI) as first-line treatments for major depressive disorder (MDD) and emphasize the importance of early pharmacological treatment as key factors to treatment success.

Objectives: To compare the MDD-related healthcare resource utilization (HCRU) and cost among patients (1) with early vs late pharmacological treatment initiation and (2) achieving minimum therapeutic dose (MTD) early vs late.

Methods: The MarketScan database (2010–2015) was used. Adults who were newly-treated with SSRI/SNRI within 12?months after the initial MDD diagnosis (index) were included. Patients who initiated SSRI/SNRI within 2?weeks of the index date were defined as early initiators; those who reached MTD within 4?weeks of index date were defined as early MTD achievers. MDD-related HCRU and costs per year after the index date were compared between early and late initiators and between early and late achievers using propensity score matching and generalized linear models.

Results: Of the 55,539 patients, 60% were early initiators and 61% were early MTD achievers. The mean number of MDD-related outpatient visits per year were significantly higher for late initiator (6.7 vs 4.2, p?<?.001) and late MTD achievers (6.5 vs 4.5, p?<?.001) vs their early counterparts. Mean annual MDD-related outpatient, drug, and total cost were significantly higher for late initiators and MTD achievers vs the early groups.

Conclusions: There is an opportunity to improve outcomes by treating MDD patients with SSRI/SNRI within 2?weeks and at or above the MTD within 4?weeks of diagnosis or less.     

Emerging antithrombotic drugs for acute coronary syndrome

Introduction: Acute coronary syndrome (ACS) encompasses acute myocardial infarction (MI) and unstable angina. Activation of platelets and coagulation cascade plays a central role in the development of ACS. Over the past decade, there have been substantial improvements in the strategies for secondary prevention of ACS, including the development of more potent oral antiplatelet agents such as prasugrel and ticagrelor. However, therapies with even better efficacy and safety profiles and more rapid onset and offset of action would be desirable.

Areas covered: This review discusses the advantages and disadvantages of the currently available antithrombotic agents and describes the findings from recent clinical trials of three novel agents; cangrelor (an intravenous P2Y12 receptor antagonist), vorapaxar (protease-activated receptor-1 inhibitor) and rivaroxaban (an oral factor Xa inhibitor).

Expert opinion: Cangrelor appears more promising than clopidogrel when a very rapid onset and reversal of antiplatelet effect is needed. Vorapaxar in addition to standard oral antiplatelet therapy was effective in patients with prior MI, but was not safe in patients with a prior stroke. Low dose rivaroxaban decreased cardiovascular events and mortality in patients post-ACS compared to placebo, although bleeding was increased.     

Efficacy of clopidogrel treatment and platelet responsiveness in peripheral arterial procedures

Introduction: Long-term antiplatelet therapy with clopidogrel has been recommended in patients undergoing peripheral arterial procedures. Poor antiplatelet effect of clopidogrel or high on-clopidogrel platelet reactivity (HCPR) has been recently identified in patients with peripheral arterial disease (PAD).

Areas covered: This review focuses on the use of clopidogrel and the phenomenon of HCPR in PAD patients treated for intermittent claudication or critical limb ischaemia (CLI). The authors summarize current guidelines and recommendations for use of clopidogrel following peripheral arterial procedures and explore the prevalence and clinical impact of HCPR in the PAD population. Underlying mechanisms of HCPR and relevant clinical and genetic factors are analyzed with particular attention to the potential utility of point-of-care platelet function testing (PFT).

Expert opinion: Clopidogrel is a safe, effective and well-tolerated antiplatelet agent in PAD patients following peripheral arterial revascularization. Dual-antiplatelet therapy could also be considered after complex endovascular procedures. HCPR has been identified in more than 50% of PAD patients on clopidogrel and has been related with significantly increased re-intervention rates. Incidence of HCPR is significantly higher in patients with CLI, diabetes mellitus and chronic renal disease. Personalized antiplatelet therapy on the basis of PFT is an elegant emerging concept for optimization of platelet inhibition and potential identification of patients at increased risk of bleeding and warrants investigation in future large-scale trials.     

Routine early versus deferred provisional tirofiban treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention

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Warfarin therapy in Chinese patients with atrial fibrillation treated with percutaneous coronary intervention: a 5 year follow-up retrospective cohort study

Objective: To evaluate warfarin use in Chinese patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) by investigating the stroke and major adverse cardiac and cerebral events (MACCEs) and bleeding events.

Methods: Retrospective cohort study of the 5?year follow-up of 1134 patients with AF who underwent PCI. The patients were grouped according to whether they received warfarin or not. Baseline characteristics and the occurrence of MACCEs and bleeding events were compared between the two groups using the CHA2DS2-VASc and HAS-BLED scoring. Cox regression analysis was used to identify factors related to the occurrence of MACCEs and bleeding.

Results: Overall MACCE (p?=?.008) and mortality (p?=?.004) rates were significantly lower in the warfarin group compared with the non-warfarin group. Major bleeding, minor bleeding and overall bleeding were comparable in the two groups. Recurrent myocardial infarction (HR?=?10.129, 95% CI?=?4.737–21.655; p?<?.001) and a baseline CHA2DS2-VASc score >4 (HR?=?2.035, 95% CI?=?1.121–3.692; p?=?.019) were independent predictors of MACCEs in the warfarin group. A baseline HAS-BLED score ≥3 (HR?=?5.498, 95% CI?=?3.773–8.013; p?<?.001) and previous bleeding (HR?=?3.058, 95% CI?=?1.319–7.088; p?=?.009) were independent predictors of bleeding.

Conclusions: Warfarin reduces the incidence of MACCEs but does not increase bleeding events in Chinese patients with AF who underwent PCI. For patients taking warfarin, recurrent myocardial infarction and a baseline CHA2DS2-VASc score >4 were related to MACCE occurrence.     

Effect of clopidogrel besylate on platelet reactivity in patients with acute coronary syndromes. Comparison with clopidogrel hydrogen sulfate

Objective: The efficacy of clopidogrel therapy in patients with an acute coronary syndrome (ACS) has been established using the clopidogrel hydrogen sulfate (CHS) formulation. In this study we compared the antiplatelet effectiveness of a generic clopidogrel salt, clopidogrel besylate (CB), with the original CHS in patients with an ACS.

Research design and methods: Ninety-six ACS patients were randomized to receive a 600-mg loading dose of either CHS (n = 45) or CB (n = 51), followed by 75 mg/day. Sixty-eight patients underwent a percutaneous coronary intervention (PCI), whereas 28 were treated conservatively. Platelet aggregatory response, vasodilator-stimulated phosphoprotein (VASP) phosphorylation, P-selectin expression and platelet–leucocyte conjugates were determined before clopidogrel loading (baseline), as well as at 5 days and at 1 month afterwards.

Results: No difference in the clopidogrel response variability was observed between patients receiving CHS or CB either at 5 days or at 1 month of follow-up. Similarly, no difference in the inhibition of platelet aggregation, P-selectin expression or in the platelet–leucocyte conjugates was observed between CHS and CB group during the follow-up.

Conclusions: There is no overall significant difference in the antiplatelet efficacy between CB and CHS during their administration in ACS patients for up to 1 month after the episode.