Platelet glycoprotein IIb/IIIa receptor antagonists in cardiovascular disease

CONTEXT: Thrombus formation on disrupted atherosclerotic plaque is the major cause of acute coronary events. Platelet inhibitors are the mainstay of drug therapy to reduce cardiac events in patients with acute coronary syndromes. The platelet glycoprotein (GP) IIb/IIIa receptor is the final common pathway of platelet aggregation. OBJECTIVES: To review mechanisms of platelet activation and aggregation and the role of the GP IIb/IIIa receptor in the acute coronary syndromes and to summarize completed clinical trials of GP IIb/IIIa receptor antagonists. DATA SOURCES: English-language journal articles, reviews from a MEDLINE search from 1993 through 1998, as well as abstracts and presentations from major national or international cardiology meetings through November 1998. STUDY SELECTION/DATA EXTRACTION: Randomized, placebo-controlled clinical trials testing intravenous GP IIb/IIIa receptor antagonists and having more than 500 subjects were included. Data quality and validity included publication or presentation venue. DATA SYNTHESIS/CONCLUSIONS: The GP IIb/IIIa receptor is the final common pathway of platelet aggregation. Intravenous monoclonal antibody and peptide and nonpeptide antagonists of the GP IIb/IIIa receptor have been tested in randomized, placebo-controlled trials of the acute coronary syndromes and percutaneous coronary interventions. For patients undergoing percutaneous revascularization, these agents have demonstrated efficacy in reducing death, myocardial infarction, or urgent reintervention. Odds ratios of death or myocardial infarction at 30 days range from 0.42 to 0.84 for the drugs in these studies. More modest benefits have been seen in trials of IIb/IIIa receptor antagonists for patients with the acute coronary syndromes, with odds ratios for death or myocardial infarction at 30 days ranging from 0.70 to 0.89. The efficacy of oral agents for chronic GP IIb/IIIa receptor antagonism has not been sufficiently studied.     

Routine upstream initiation vs deferred selective use of glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: the ACUITY Timing trial

Context  In patients with moderate- and high-risk acute coronary syndromes (ACS) who undergo an early, invasive treatment strategy, current guidelines recommend administration of platelet glycoprotein IIb/IIIa (Gp IIb/IIIa) inhibitors, either upstream to all patients prior to angiography or deferred for selective use in the catheterization laboratory just prior to angioplasty. The preferred approach is undetermined. Objective  To determine the optimal strategy for the use of Gp IIb/IIIa inhibitors in patients with moderate- and high-risk ACS undergoing an early, invasive treatment strategy. Design  Prospective, randomized, open-label trial with 30-day clinical follow-up. Setting  Four hundred fifty academic and community-based institutions in 17 countries. Patients  A total of 9207 patients with moderate- and high-risk ACS undergoing an invasive treatment strategy. Interventions  Patients were randomly assigned to receive either routine upstream (n=4605) or deferred selective (n=4602) Gp IIb/IIIa inhibitor administration, respectively. Main Outcome Measures  The primary outcome was assessment of noninferiority of deferred Gp IIb/IIIa inhibitor use compared with upstream administration for the prevention of composite ischemic events (death, myocardial infarction, or unplanned revascularization for ischemia) at 30 days, using a 1-sided level of .025. Major secondary end points included noninferiority or superiority of major bleeding and net clinical outcomes (composite ischemia or major bleeding). Results  Glycoprotein IIb/IIIa inhibitors were used more frequently (98.3% vs 55.7%, respectively) and for a significantly longer duration (median, 18.3 vs 13.1 hours; P<.001) in patients in the upstream group compared with the deferred group. Composite ischemia at 30 days occurred in 7.9% of patients assigned to deferred use compared with 7.1% of patients assigned to upstream administration (relative risk, 1.12; 95% confidence interval, 0.97-1.29; P = .044 for noninferiority; P = .13 for superiority); as such, the criterion for noninferiority was not met. Deferred use compared with upstream use resulted in reduced 30-day rates of major bleeding (4.9% vs 6.1%, respectively; P<.001 for noninferiority; P = .009 for superiority) and similar rates of net clinical outcomes (11.7% vs 11.7%; P<.001 for noninferiority; P = .93 for superiority). Conclusions  Among patients with moderate- and high-risk ACS undergoing an invasive treatment strategy, deferring the routine upstream use of Gp IIb/IIIa inhibitors for selective administration in the cardiac catheterization laboratory only to patients undergoing percutaneous coronary intervention resulted in a numerical increase in composite ischemia that, while not statistically significant, did not meet the criterion for noninferiority. This finding was offset by a significant reduction in major bleeding. Trial Registration  ClinicalTrials.gov Identifier: NCT00093158      

Early vs late administration of glycoprotein IIb/IIIa inhibitors in primary percutaneous coronary intervention of acute ST-segment elevation myocardial infarction: a meta-analysis

Context  Glycoprotein IIb/IIIa (Gp IIb/IIIa) inhibitors improve myocardial reperfusion and clinical outcomes of patients undergoing primary percutaneous coronary intervention (PCI), but optimal timing of administration remains unclear. No systematic reviews have comprehensively examined the effects of early vs delayed administration of these agents. Objective  To perform a meta-analysis of randomized trials of early (prior to transfer to the catheterization laboratory) vs late (at the time of PCI) intravenous administration of Gp IIb/IIIa inhibitors in acute ST-segment elevation myocardial infarction (STEMI). Data Sources  MEDLINE and the Cochrane Controlled Trials Register search of the literature over the past 10 years; papers presented at major cardiac conferences; consultation with national and international colleagues as well as Gp IIb/IIIa inhibitor drug manufacturers; and text and journal article bibliographies. Study Selection and Data Extraction  We examined trials of randomized comparisons between early administration at the point of initial contact (emergency department or ambulance) and late administration (catheterization laboratory) of Gp IIb/IIIa inhibitors in STEMI. Outcome data had to be available on both culprit artery patency evaluated by Thrombolysis in Myocardial Infarction (TIMI) flow grades on admission and mortality. Two authors independently reviewed abstracts or complete articles. Six studies met inclusion criteria. Independent data extraction was performed by 2 reviewers and confirmed by consensus. Data Synthesis  The 6 trials enrolled 931 STEMI patients treated with abciximab (3 trials) or tirofiban (3 trials) in combination with primary PCI. TIMI grade 2 or 3 flow (41.7% [194/465 vs 29.8% [139/466]) as well as TIMI grade 3 flow (20.3% [84/413] vs 12.2% [51/418]) were significantly more frequent in the early group compared with the late group (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.28-2.22; P<.001; and OR, 1.85; 95% CI, 1.26-2.71; P<.001, respectively). The early administration of Gp IIb/IIIa inhibitors was associated with a 28% reduction of mortality from 4.7% to 3.4%, which was not significant but consistent with similar trends for reinfarction and the composite ischemic end point. Conclusions  In a meta-analysis of 6 randomized trials, early administration of Gp IIb/IIIa inhibitors in STEMI appeared to improve coronary patency with favorable trends for clinical outcomes. These findings are supportive of a strategy of facilitated PCI. Further evaluations in adequately powered large trials are awaited to confirm the clinical benefit of this strategy.      

Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention: REPLACE-2 randomized trial

Context  The direct thrombin inhibitor bivalirudin has been associated with better efficacy and less bleeding than heparin during coronary balloon angioplasty but has not been widely tested during contemporary percutaneous coronary intervention (PCI). Objective  To determine the efficacy of bivalirudin, with glycoprotein IIb/IIIa (Gp IIb/IIIa) inhibition on a provisional basis for complications during PCI, compared with heparin plus planned Gp IIb/IIIa blockade with regard to protection from periprocedural ischemic and hemorrhagic complications. Design, Setting, and Participants  The Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)–2 trial, a randomized, double-blind, active-controlled trial conducted among 6010 patients undergoing urgent or elective PCI at 233 community or referral hospitals in 9 countries from October 2001 through August 2002. Interventions  Patients were randomly assigned to receive intravenous bivalirudin (0.75-mg/kg bolus plus 1.75 mg/kg per hour for the duration of PCI), with provisional Gp IIb/IIIa inhibition (n = 2999), or heparin (65-U/kg bolus) with planned Gp IIb/IIIa inhibition (abciximab or eptifibatide) (n = 3011). Both groups received daily aspirin and a thienopyridine for at least 30 days after PCI. Main Outcome Measures  The primary composite end point was 30-day incidence of death, myocardial infarction, urgent repeat revascularization, or in-hospital major bleeding; the secondary composite end point was 30-day incidence of death, myocardial infarction, or urgent repeat revascularization. Results  Provisional Gp IIb/IIIa blockade was administered to 7.2% of patients in the bivalirudin group. By 30 days, the primary composite end point had occurred among 9.2% of patients in the bivalirudin group vs 10.0% of patients in the heparin-plus-Gp IIb/IIIa group (odds ratio, 0.92; 95% confidence interval, 0.77-1.09; P = .32). The secondary composite end point occurred in 7.6% of patients in the bivalirudin vs 7.1% of patients in the heparin-plus-Gp IIb/IIIa groups (odds ratio, 1.09; 95% confidence interval 0.90-1.32; P = .40). Prespecified statistical criteria for noninferiority to heparin plus Gp IIb/IIIa were satisfied for both end points. In-hospital major bleeding rates were significantly reduced by bivalirudin (2.4% vs 4.1%; P<.001). Conclusions  Bivalirudin with provisional Gp IIb/IIIa blockade is statistically not inferior to heparin plus planned Gp IIb/IIIa blockade during contemporary PCI with regard to suppression of acute ischemic end points and is associated with less bleeding.      

Long-term efficacy of bivalirudin and provisional glycoprotein IIb/IIIa blockade vs heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary revascularization: REPLACE-2 randomized trial

Context  In the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial, bivalirudin with provisional glycoprotein IIb/IIIa (Gp IIb/IIIa) inhibition was found to be noninferior to heparin plus planned Gp IIb/IIIa blockade in the prevention of acute ischemic end points and was associated with significantly less bleeding by 30 days after percutaneous coronary intervention (PCI). Objective  To determine whether the efficacy of bivalirudin remains comparable with that of heparin plus Gp IIb/IIIa blockade over 6 months and 1 year. Design, Setting, and Participants  Follow-up study to 1 year of a randomized, double-blind trial conducted among 6010 patients undergoing urgent or elective PCI at 233 community or referral hospitals in 9 countries from October 2001 through August 2002. Interventions  Patients were randomly assigned to receive intravenously bivalirudin (0.75 mg/kg bolus, 1.75 mg/kg per hour for the duration of PCI), with provisional Gp IIb/IIIa inhibition, or to receive heparin (65 U/kg bolus), with planned Gp IIb/IIIa inhibition (abciximab or eptifibatide). Both groups received daily aspirin and a thienopyridine for at least 30 days after PCI. Main Outcome Measures  Incidence of death, myocardial infarction, or repeat revascularization by 6 months and death by 12 months after enrollment. Results  At 6 months, death occurred in 1.4% of patients in the heparin plus Gp IIb/IIIa group and in 1.0% of patients in the bivalirudin group (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.43-1.14; P = .15). Myocardial infarction occurred in 7.4% and 8.2% of patients, respectively (HR, 1.12; 95% CI, 0.93-1.34; P = .24), and repeat revascularization was required in 11.4% and 12.1% of patients, respectively (HR, 1.06; 95% CI, 0.91-1.23; P = .45). By 1 year, death occurred in 2.46% of patients treated with heparin plus Gp IIb/IIIa blockade and in 1.89% of patients treated with bivalirudin (HR, 0.78; 95% CI, 0.55-1.11; P = .16). Nonsignificant trends toward lower 1-year mortality with bivalirudin were present in all patient subgroups analyzed and were of greatest magnitude among high-risk patients. Conclusion  Long-term clinical outcome with bivalirudin and provisional Gp IIb/IIIa blockade is comparable with that of heparin plus planned Gp IIb/IIIa inhibition during contemporary PCI.      

ST段抬高心肌梗死行介入治疗患者冠脉相对于静脉使用Ⅱb/Ⅲa受体拮抗剂临床效果的Meta分析

目的系统评价ST段抬高心肌梗死(ST segment elevation myocardial infarction,STEMI)行经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)患者,冠脉较静脉使用血小板糖蛋白(platelet glycoprotein,GP)Ⅱb/Ⅲa受体拮抗剂的有效性及安全性。方法 2011年9月至10月,计算机检索美国国立生物医学信息中心PubMed数据库、Cochrane图书馆临床对照试验数据库、荷兰医学文摘embase数据库、中国生物医学文献数据库(CBM)和中国期刊全文数据库(CJFD)。同时检索相关网站,尽量获取会议摘要及灰色文献。使用RevMan 5.1软件对纳入研究进行Meta分析。结果共纳入11篇文献,总计1 569例患者。Meta分析结果示:冠脉较静脉使用GPⅡb/Ⅲa受体拮抗剂能显著改善STEMI患者术后心肌梗死溶栓试验(TIMI)3级血流(RR=1.08,95%CI为1.04～1.13,P<0.01),TIMI心肌组织灌注分级(TMPG)3级血流(RR=1.37,95%CI为1.16～1.63,P<0.01),左室射血分数(MD=0.04,95%CI为0.02～0.06,P<0.01),降低主要不良心脏事件(MACE)发生率(RR=0.48,95%CI为0.34～0.69,P<0.01),同时不增加主要出血并发症(RR=1.04,95%CI为0.55～1.95,P=0.90)。阿昔单抗在此基础上能进一步降低1个月时死亡率(RR=0.45,95%CI为0.21～0.99,P=0.05)。结论冠脉较静脉途径使用GPⅡb/Ⅲa受体拮抗剂能改善STEMI行PCI治疗患者术后罪犯血管再通、心肌灌注及左心室功能恢复,降低主要不良心脏事件发生率,同时不增加主要出血并发症。     

自身反应性T淋巴细胞在抗血小板抗体产生中的作用

目的 探讨自身反应性T淋巴细胞在抗血小板抗体产生中的作用.方法 采用亲和层析柱分离血小板膜糖蛋白GPⅡb/Ⅲa,并以此为抗原刺激ITP患者(实验组)和正常人(正常对照组)的单个核细胞,观察单个核细胞的增殖活化情况及IL-6、抗GPⅡb/Ⅲa IgG抗体产生水平.结果 实验组单个核细胞的增殖数量明显多于正常对照组,且增殖的细胞以T细胞为主,CD4 T细胞略高于对照组, 实验组CD28 、CD25 T淋巴细胞均明显高于对照组.在9例增殖的ITP患者单个核细胞培养的上清液中检测到高于正常对照组的IL-6和抗GPⅡb/Ⅲa IgG抗体水平,12例ITP患者中3例T淋巴细胞增生不明显,其IL-6和抗GPⅡb/Ⅲa IgG抗体水平亦很低,对照组虽然有淋巴细胞的增殖,但在体外培养过程中产生的相应抗体含量极低.结论 GPⅡb/Ⅲa 抗原刺激增强了抗GPⅡb/Ⅲa IgG抗体的产生, 对GPⅡb/Ⅲa自身反应的T淋巴细胞在激活B细胞及抗GPⅡb/Ⅲa IgG抗体的产生中起到了重要作用.     

The role of inflammatory stress in acute coronary syndrome

Objective To summarize current understanding of the roles of anti-inflammatory and proinflammatory mechanisms in the development of atherosclerosis and acute coronary syndrome and to postulate the novel concept of inflammation stress as the most important factor triggering acute coronary syndrome. Moreover, markers of inflammation stress and ways ,to block involved pathways are elucidated.Data sources A literature search(MEDLINE 1997 to 2002) was performed using the key words “inflammation and cardiovascular disease”. Relevant book chapters were also reviewed.Study selection Well-controlled, prospective landmark studies and review articles on inflammation and acute coronary syndrome were selected.Data extraction Data and conclusions from the selected articles providing solid evidence to elucidate the mechanisms of inflammation and acute coronary syndrome were extracted and interpreted in the light of our own clinical and basic research.Data synthesis Inflammation is closely linked to atherosclerosis and acute coronary syndrome.Chronic and long-lasting inflammation stress, present both systemically or in the vascular walls, can trigger acute coronary syndrome.Conclusions Inflammation stress plays an important role in the process of acute coronary syndrome.Drugs which can modulate the balance of pro- and anti-inflammatory processes and attenuate inflammation stress, such as angiotensin-converting enzyme (ACE) inhibitors/angiotensin Ⅱ receptor blockers, statins, and cytokine antagonists may play active roles in the prevention and treatment of acute coronary syndrome when used in addition to conventional therapies (glycoprotein Ⅱ b/Ⅲ a receptor antagonists, mechanical intervention strategies, etc).     

Antithrombotic strategies in patients with acute coronary syndromes undergoing early invasive management: one-year results from the ACUITY trial

Gregg W. Stone, MD; James H. Ware, PhD; Michel E. Bertrand, MD; A. Michael Lincoff, MD; Jeffrey W. Moses, MD; E. Magnus Ohman, MD; Harvey D. White, MD; Frederick Feit, MD; Antonio Colombo, MD; Brent T. McLaurin, MD; David A. Cox, MD; Steven V. Manoukian, MD; Martin Fahy, MSc; Tim C. Clayton, MSc; Roxana Mehran, MD; Stuart J. Pocock, PhD; for the ACUITY Investigators

JAMA. 2007;298(21):2497-2506.

Context  At 30-day follow-up, patients with moderate- and high-risk acute coronary syndromes (ACS) undergoing early invasive treatment in the ACUITY trial with bivalirudin monotherapy vs heparin plus glycoprotein (GP) IIb/IIIa inhibitors had noninferior rates of adverse ischemic events with reduced rates of major bleeding. Deferred upstream use of GP IIb/IIIa inhibitors for selective administration to patients undergoing percutaneous coronary intervention (PCI) resulted in a significant reduction in major bleeding, although a small increase in composite ischemia could not be excluded.

Objective  To determine 1-year ischemic outcomes for patients in the ACUITY trial.

Design, Setting, and Patients  A prospective, randomized, open-label trial with 1-year clinical follow-up at 450 academic and community-based institutions in 17 countries. A total of 13 819 patients with moderate- and high-risk ACS undergoing invasive treatment were enrolled between August 23, 2003, and December 5, 2005.

Interventions  Patients were assigned to heparin plus GP IIb/IIIa inhibitors (n = 4603), bivalirudin plus GP IIb/IIIa inhibitors (n = 4604), or bivalirudin monotherapy (n = 4612). Of these patients, 4605 were assigned to routine upstream GP IIb/IIIa administration and 4602 were deferred to selective GP IIb/IIIa inhibitor administration.

Main Outcome Measure  Composite ischemia (death, myocardial infarction, or unplanned revascularization for ischemia) at 1 year.

Results  Composite ischemia at 1 year occurred in 15.4% of patients assigned to heparin plus GP IIb/IIIa inhibitors and 16.0% assigned to bivalirudin plus GP IIb/IIIa inhibitors (compared with heparin plus GP IIb/IIIa inhibitors, HR, 1.05; 95% CI, 0.95-1.16; P = .35), and 16.2% assigned to bivalirudin monotherapy (HR, 1.06; 95% CI, 0.95-1.17; P = .29). Mortality at 1 year occurred in an estimated 3.9% of patients assigned to heparin plus GP IIb/IIIa inhibitors, 3.9% assigned to bivalirudin plus GP IIb/IIIa inhibitors (HR, 0.99; 95% CI, 0.80-1.22; P = .92), and 3.8% assigned to bivalirudin monotherapy (HR, 0.96; 95% CI, 0.77-1.18; P = .67). Composite ischemia occurred in 16.3% of patients assigned to deferred use compared with 15.2% of patients assigned to upstream administration (HR, 1.08; 95% CI, 0.97-1.20; P = .15).

Conclusions  At 1 year, no statistically significant difference in rates of composite ischemia or mortality among patients with moderate- and high-risk ACS undergoing invasive treatment with the 3 therapies was found. There was no statistically significant difference in the rates of composite ischemia between patients receiving routine upstream administration of GP IIb/IIIa inhibitors vs deferring their use for patients undergoing PCI.

Trial Registration  clinicaltrials.gov Identifier: NCT00093158

     

Excess dosing of antiplatelet and antithrombin agents in the treatment of non-ST-segment elevation acute coronary syndromes

Context  Effective medical care assumes delivery of evidence-based medicines to appropriate patients with doses comparable to those studied. Objective  To investigate dosing of unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and glycoprotein IIb/IIIa inhibitors, and the association between dosing and major outcomes. Design, Setting, and Participants  A prospective observational analysis in 387 US academic and nonacademic hospitals of 30 136 patients from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines) National Quality Improvement Initiative Registry who had non–ST-segment elevation acute coronary syndromes (NSTE ACS) with chest pain and either positive electrocardiograms or cardiac biomarkers between January 1 and September 30, 2004. Main Outcome Measures  Excessive dosing of UFH, LMWH, and glycoprotein IIb/IIIa inhibitors and major clinical outcomes, including bleeding, in-hospital mortality, and length of stay. Results  A total of 3354 patients (42%) with NSTE ACS who were administered antithrombotic agents received at least 1 initial dose outside the recommended range. An excess dose was administered to 2934 patients (32.8%) treated with UFH, 1378 (13.8%) treated with LMWH, and 2784 (26.8%) treated with glycoprotein IIb/IIIa inhibitors. Factors associated with excess dosing included older age, as well as female sex, renal insufficiency, low body weight, diabetes mellitus, and congestive heart failure. Relative to those patients not administered excess dosages, patients with excess dosages of UFH, LMWH, and glycoprotein IIb/IIIa inhibitors either tended toward or had higher risks for major bleeding (adjusted odds ratio [OR], 1.08; 95% confidence interval [CI], 0.94-1.26; OR, 1.39; 95% CI, 1.11-1.74; and OR, 1.36; 95% CI, 1.10-1.68; respectively). Bleeding increased relative to the degree of excess dose and to the number of agents administered in excess (6.6% [237/3590] if neither heparin nor glycoprotein IIb/IIIa excess vs 22.2% [93/419] if both excess). Mortality and length of stay were also higher among those patients administered excess dosing. We estimated that 15% (400/2766) of major bleeding in this population may be attributable to excess dosing. Conclusions  Patients with NSTE ACS treated in the community often receive excess doses of antithrombotic therapy. Dosing errors occur more often in vulnerable populations and predict an increased risk of major bleeding.      

血小板膜糖蛋白Ⅱb／Ⅲa受体激活在再灌注心肌无复流形成中的作用

OBJECTIVE: To observe the changes in the activity of platelet glycoprotein (GP) IIb/IIIa receptor following the occurrence of no-reflow after myocardial reperfusion, to explore the measures for clinical management of this condition. METHODS: Nine canine models of no-reflow following myocardial ischemia verified by reperfusion myocardial contrast echocardiography were used in this investigation. The peripheral venous blood (PVB) and sinus venous blood (SVB) were sampled before myocardial reperfusion (after a 3-hour myocardial ischemia) and after a 3-hour reperfusion for determinating GP IIb/IIIa receptor activities by means of enzyme-linked immunosorbent assay (ELISA). RESULTS: The activity of platelet GP IIb/IIIa of PVB, either in 3-hour ischemic group or in 3-hour reperfusion group, was elevated significantly (P < 0.001), suggesting platelet activation. Elevated platelet GP IIb/IIIa receptor activity in SVB occurred only in 3-hour ischemic group, and the 3-hour reperfusion group (P < 0.001) and the no-reflow group had significantly decreased activities, which was more obvious in the latter group (P < 0.01). The findings signified the consumption of the platelet GP IIb/IIIa receptors in the myocardial microcirculation and the presence of platelet aggregation. CONCLUSIONS: Myocardial ischemia may activate the platelets to express GP IIb/IIIa receptors through stress response mechanism and damage the endothelia of the microvasculature to incur adhesion and aggregation of the platelets within the microcirculation, which may be one of the pathogeneses for myocardial no-reflow phenomenon.     

Antiplatelet therapy in non-ST-segment elevation acute coronary syndromes

Acute coronary syndromes are a frequent cause of hospital admission for patients with coronary artery disease. The pathophysiology of acute coronary syndromes often involves plaque rupture or fissure with platelet aggregation. Recognition of the importance of platelet aggregation resulted in several large randomized trials testing 3 types of platelet antagonists, aspirin, glycoprotein IIb/IIIa inhibitors, and adenosine diphosphate inhibitors. A thorough understanding of the data, risks, and benefits of these therapies is important to optimize treatment of the patient with an acute coronary syndrome. Recognition that there is a great deal of interpatient variability in response to these antiplatelet therapies highlights the need for future research in this area.     

Troponin: the biomarker of choice for the detection of cardiac injury

It has been known for 50 years that transaminase activity increases in patients with acute myocardial infarction. With the development of creatine kinase (CK), biomarkers of cardiac injury began to take a major role in the diagnosis and management of patients with acute cardiovascular disease. In 2000 the European Society of Cardiology and the American College of Cardiology recognized the pivotal role of biomarkers and made elevations in their levels the “cornerstone” of diagnosis of acute myocardial infarction. At that time, they also acknowledged that cardiac troponin I and T had supplanted CK-MB as the analytes of choice for diagnosis. In this review, we discuss the science underlying the use of troponin biomarkers, how to interpret troponin values properly and how to apply these measurements to patients who present with possible cardiovascular disease.     

再生障碍性贫血血小板相关抗体及血浆抗血小板膜糖蛋白抗体检测

对74例再生障碍性贫血患者进行了血小板相关抗体(PAIgG、PAIgA、PAIgM、PAC_3)及血浆中抗血小板膜糖蛋白(GP Ib、GP Ⅱb/Ⅲa)抗体的测定。结果表明,PAIgG和PAIgM增高有显著性,29.6％的患者血浆中可检出抗GP Ib及/或抗GP Ⅱb/Ⅲa抗体、提示病理免疫机制可能参与再障血小板异常的作用。     

Why we need a national registry in interventional cardiology

Percutaneous coronary intervention (PCI) is increasingly used in the management of acute coronary syndromes and refractory angina, and technical advances such as drug-eluting stents (DES) and potent antithrombotic therapies (such as clopidogrel and glycoprotein IIb/IIIa inhibitors) have been heralded as improving long-term outcomes. Offsetting these advances has been: considerable concern about the safety of DES in regard to late stent thrombosis and antithrombotic drug-induced bleeding; the rising use of PCI and DES in clinical situations where evidence of efficacy is lacking; preferential use of PCI in low-risk populations; and limited cost-effectiveness data comparing PCI with other treatments. There are few contemporary data in Australia on the efficacy, safety and costs of PCI - as used in everyday clinical practice - that matches clinical outcomes with baseline patient characteristics, indications for intervention, coronary anatomy, procedural technique, co-interventions and site of care. A national registry that prospectively collects standardised data on processes and outcomes of PCI is warranted. This would ensure safe and appropriate evidence-based use of limited resources in an era of expanding use of PCI in clinical circumstances not tested in randomised trials.     

Production and application of anti-human platelet GP IIb/IIIa monoclonal antibodies

Four types of anti-human platelet glycoprotein IIb/IIIa (GP IIb/IIIa)monoclonal antibodies (McAb), termed HIP2, HIP4, HIP7, HIP8, were obtained in our laboratory. All of them recognized GP IIb/IIIa complex except that HIP2 recognized GP IIb. As to the effect of the four McAbs on platelet aggregation, the results showed: 1) HIP4 and HIP8 can completely inhibit platelet aggregation induced by ADP or collagen, but not that induced by thrombin or ristocetin. 2) HIP2 was able to activate platelet aggregation directly. But it is Ca++ and complement dependent; 3) HIP7 did not show any effect on platelet aggregation induced by collagen, ADP, thrombin or ristocetin. When clinically studied, some cases of platelet-associated diseases such as thrombocytasthenia and thrombocytopenia had abnormal responses to the above McAbs. In addition, we also found that these McAbs can stimulate hematopoiesis in CFU-E assay.     

2020年美国心脏病学会《降低2型糖尿病患者心血管风险新型疗法的专家共识决策路径》解读：降糖更要护心

基金项目：上海市卫生健康委员会科研课题（202040368） 心血管疾病在2型糖尿病（T2DM）患者中的发病率居高不下,并且是T2DM患者死亡的主要原因。不断优化临床治疗策略以改善T2DM患者心血管事件预后是临床医生对糖尿病患者治疗的首要任务。近些年大量研究证实钠-葡萄糖协同转运蛋白2（SGLT-2）抑制剂和胰高血糖素样肽1受体激动剂（GLP-1RA）可以显著降低T2DM患者主要不良心血管事件的发生风险。近日美国心脏病学会依据最新的临床研究证据,发布了《降低2型糖尿病患者心血管风险新疗法的专家共识决策路径》,本文结合该共识对SGLT-2抑制剂和GLP-1RA两类新型降糖药物治疗策略进行了解读,希望为临床医生提供简洁、实用的新型降糖药物治疗指导,以优化临床治疗策略,实现改善T2DM患者预后的目的。     

Bolus fibrinolytic therapy in acute myocardial infarction

CONTEXT: New bolus fibrinolytics derived from the human tissue-type plasminogen activator (tPA) have emerged as a means of dissolution of occlusive thrombosis associated with acute myocardial infarction. OBJECTIVE: To review the new bolus fibrinolytic drugs derived from tPA: reteplase, lanoteplase, and tenecteplase. DATA SOURCES: The MEDLINE, EMBASE, and Current Contents databases were searched for articles from 1983 to 2001, using the index terms pharmacokinetics, pharmacodynamics, plasminogen activator, reteplase, lanoteplase, and tenecteplase. Additional data sources included bibliographies of articles identified on MEDLINE, EMBASE, and Current Content, inquiry of experts and pharmaceutical companies, and preliminary data presented at recent national and international cardiology conferences. STUDY SELECTION: We selected for review studies that evaluated the pharmacokinetics and pharmacodynamics of reteplase, lanoteplase, and tenecteplase, and assessed the effects of these bolus fibrinolytic drugs on the angiographic and immediate and long-term outcomes of patients. Of 138 articles identified, 38 were analyzed. DATA EXTRACTION: Data quality was determined by publication in the peer-reviewed literature or presentation at an official cardiology society-sponsored meeting. DATA SYNTHESIS: Tenecteplase and reteplase are comparable with accelerated infusion recombinant tPA in terms of efficacy and safety but more convenient because they are administered by bolus injection. Lanoteplase and heparin bolus plus infusion is as effective as tPA with regard to mortality, but the rate of intracranial hemorrhage is significantly higher. CONCLUSION: Given the ease of administration and the similar outcomes compared with accelerated infusion recombinant tPA, it is likely that a key component of contemporary reperfusion will include a bolus fibrinolytic.     

Use of low-molecular-weight heparins in the management of acute coronary artery syndromes and percutaneous coronary intervention

Context  Low-molecular-weight heparins (LMWHs) possess several potential pharmacological advantages over unfractionated heparin as an antithrombotic agent. Objective  To systematically summarize the clinical data on the efficacy and safety of LMWHs compared with unfractionated heparin across the spectrum of acute coronary syndromes (ACSs), and as an adjunct to percutaneous coronary intervention (PCI). Data Sources  We searched MEDLINE for articles from 1990 to 2002 using the index terms heparin, enoxaparin, dalteparin, nadroparin, tinzaparin, low molecular weight heparin, myocardial infarction, unstable angina, coronary angiography, coronary angioplasty, thrombolytic therapy, reperfusion, and drug therapy, combination. Additional data sources included bibliographies of articles identified on MEDLINE, inquiry of experts and pharmaceutical companies, and data presented at recent national and international cardiology conferences. Study Selection  We selected for review randomized trials comparing LMWHs against either unfractionated heparin or placebo for treatment of ACS, as well as trials and registries examining clinical outcomes, pharmacokinetics, and/or phamacodynamics of LMWHs in the setting of PCI. Of 39 studies identified, 31 fulfilled criteria for analysis. Data Extraction  Data quality was determined by publication in the peer-reviewed literature or presentation at an official cardiology society–sponsored meeting. Data Synthesis  The LMWHs are recommended by the American Heart Association and the American College of Cardiology for treatment of unstable angina/non–ST-elevation myocardial infarction. Clinical trials have demonstrated similar safety with LMWHs compared with unfractionated heparin in the setting of PCI and in conjunction with glycoprotein IIb/IIIa inhibitors. Finally, LMWHs show promise as an antithrombotic agent for the treatment of ST-elevation myocardial infarction. Conclusions  The LMWHs could potentially replace unfractionated heparin as the antithrombotic agent of choice across the spectrum of ACSs. In addition, they show promise as a safe and efficacious antithrombotic agent for PCI. However, further study is warranted to define the benefit of LMWHs in certain high-risk subgroups before their use can be universally recommended.      

Anticoagulation with low-molecular-weight heparin in patients with heart diseases

Low-molecular-weight heparins (LMWH) were investigated in different cardiac diseases requiring anticoagulation. In case of short term usage advantages over intravenous unfractionated heparin (UFH) are of relevance, such as simple subcutaneous application, possibility for outpatient treatment and predictable effect on anticoagulation enabling abstention of laboratory monitoring in most cases. Thromboprophylaxis in acute medically ill patients and therapy of non-ST-elevation acute coronary syndromes (NSTE-ACS) are important indications, in which significant advantages for special LMWH as compared to Placebo or UFH were shown. A significant effect versus Placebo was demonstrated for the LMWH Dalteparin in prolonged anticoagulation until revascularisation procedure in NSTE-ACS. Promising results from trials were also published concerning use of LMWH Dalteparin and Enoxaparin in TEE-guided cardioversion. Findings from cohort trials are available for temporary or long term switch from oral anticoagulation to LMWH. Due to limited data, determination of individual benefit-to-risk ratio is of special importance to select suitable anticoagulation regimen in this case. Further investigations as a basis of general recommendations on standard dosing regimen are outstanding for use of each LMWH in percutaneous coronary interventions, as combination with Glycoprotein IIb/IIIa-inhibitors, in acute myocardial infarction and in artificial heart valves. In cardiology, most studies were performed with Dalteparin and Enoxaparin, suggesting these to be used in established cardiac indications as well as in further investigations.