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.      

Platelet glycoprotein IIb/IIIa integrin blockade with eptifibatide in coronary stent intervention: the ESPRIT trial: a randomized controlled trial

CONTEXT: The Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial showed the efficacy of adjunctive, double-bolus eptifibatide therapy in reducing ischemic complications of nonurgent coronary stent implantation at 48 hours and at 30 days. OBJECTIVE: To determine whether the beneficial effects of eptifibatide persist at 6 months after treatment. DESIGN: Follow-up study of a randomized, double-blind, placebo-controlled, crossover-permitted trial conducted from June 1999 through February 2000. SETTING: Ninety-two tertiary care centers in the United States and Canada. PARTICIPANTS: A total of 2064 patients scheduled to undergo nonurgent percutaneous coronary intervention with stent implantation. INTERVENTION: Patients were randomly assigned to receive placebo or eptifibatide (two 180-microg/kg boluses 10 minutes apart and continuous infusion of 2.0 microg/kg per minute), started immediately before stent implantation and continued for 18 to 24 hours. Complete follow-up data were available for 988 (95.0%) of 1040 patients given eptifibatide and 977 (95.4%) of 1024 patients given placebo. MAIN OUTCOME MEASURES: Composite rates of death or myocardial infarction (MI); death, MI, or target vessel revascularization; and their individual components 6 months after enrollment, compared between the 2 groups. RESULTS: By 6 months, the composite end point of death or MI had occurred in 7.5% of eptifibatide-treated patients and in 11.5% of placebo-treated patients (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.47-0.84; P =.002). The composite of death, MI, or target vessel revascularization was 14.2% in eptifibatide-treated patients vs 18.3% in placebo-treated patients (HR, 0.75; 95% CI, 0.60-0.93; P =.008). Most of this benefit accrued early (<48 hours after initiation of therapy) and was maintained through 6 months. Six-month mortality in the eptifibatide group was 0.8% vs 1.4% in the placebo group (HR, 0.56; 95% CI, 0.24-1.34; P =.19) and target vessel revascularization occurred in 8.6% of the eptifibatide group vs 9.4% of the placebo group (HR, 0.91; 95% CI, 0.68-1.22; P =.51). CONCLUSION: Adjunctive eptifibatide therapy during coronary stent implantation provides benefit through 6-month follow-up.     

Long-term efficacy of platelet glycoprotein IIb/IIIa integrin blockade with eptifibatide in coronary stent intervention

Context  In the Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial, treatment with eptifibatide, a platelet glycoprotein IIb/IIIa integrin blocker, was found to reduce the ischemic complications of nonurgent coronary stent implantation at 48 hours and 30 days. Objective  To determine whether eptifibatide treatment continues to provide durable, long-term benefit after coronary stent intervention. Design and Setting  The ESPRIT trial was a randomized, double-blind, placebo-controlled, parallel-group, crossover-permitted trial conducted from June 1999 through February 2000 at 92 tertiary care centers in the United States and Canada. Participants  A total of 2064 patients scheduled to undergo nonurgent percutaneous coronary intervention with stent implantation. Intervention  Patients were randomly assigned to receive placebo (n = 1024) or eptifibatide (two 180-µg/kg boluses, 10 minutes apart, with a continuous infusion of 2.0 µg/kg per minute; n = 1040), started immediately before stent implantation and continued for 18 to 24 hours. Patients also received aspirin, heparin, and a thienopyridine. Main Outcome Measures  Composite rates of death or myocardial infarction (MI) and death, infarction, or target vessel revascularization during the 12 months after enrollment. Results  Complete follow-up data were available for 988 patients given eptifibatide (95.0%) and 976 patients given placebo (95.3%). By 12 months, the composite of death or MI had occurred in 8.0% of eptifibatide-treated patients and in 12.4% of placebo-treated patients (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.48-0.83; P = .001). The composite rate of death, MI, or target vessel revascularization was 17.5% in eptifibatide-treated patients vs 22.1% in placebo-treated patients (HR, 0.76; 95% CI, 0.63-0.93; P = .007). Conclusions  Long-term outcomes of nonurgent coronary stent implantation appear to be improved through blockade of the platelet glycoprotein IIb/IIIa integrin with eptifibatide.      

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.      

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      

Thorombolytic therapy with rescue percutaneous coronary intervention versus primary percutaneous coronary intervention in patients with acute myocardial infarction: a multicenter randomized clinical trial

Background Although thrombolytic therapy with rescue percutaneous coronary intervention （PCI） is a common treatment strategy for ST-segment elevation acute myocardial infarction （STEMI）, scant data are available on its efficacy relative to primary PCI, and comparison was therefore the aim of this study. Methods This multicenter, open-label, randomized, parallel trial was conducted in 12 hospitals on patients （age 〈70 years） with STEMI who presented within 12 hours of symptom onset （mean interval 〉3 hours）. Patients were randomized to three groups： primary PCI group （n=101）; recombinant staphylokinase （r-Sak） group （n=-104）; and recombinant tissue-type plasminogen activator （rt-PA） group （n=-106）. For all patients allocated to the thrombolytic therapy arm, coronary angiography was performed at 90 minutes after drug therapy to confirm infarct-related artery （IRA） patency; rescue PCI was performed in cases with TIMI flow grade 〈2. Bare-metal stent implantation was planned for all patients. Results After randomization it required an average of 113.4 minutes to start thrombolytic therapy （door-to-needle time）and 141.2 minutes to perform first balloon inflation in the IRA （door to balloon time）. Rates of IRA patency （TIMI flow grade 2 or 3） and TIMI flow grade 3 were significantly lower in the thrombolysis group at 90 minutes after drug therapy than in the primary PCI group at the end of the procedure （70.5% vs. 98.0%, P 〈0.0001, and 53.0% vs. 85.9%, P 〈0.0001, respectively）. Rescue PCI with stenting was performed in 117 patients （55.7%） in the thrombolytic therapy arm. Rates of patency and TIMI flow grade 3 were still significantly lower in the rescue PCI than in the primary PCI group （88.9% vs. 97.9%, P=-0.0222, and 68.4% vs. 85.0%, P=0.0190, respectively）. At 30 days post-therapy, mortality rate was significantly higher in the thrombolysis combined with rescue PCI group than in primary PCI group （7.1% vs. 0, P=0.0034）. Rates of death/MI and bleeding complications were significantly higher in the thrombolysis with rescue PCI group than in the primary PCI group （10.0% vs. 1.0%, P=-0.0380, and 28.10% vs. 8.91%, P=-0.O001, respectively）. Conclusions Thrombolytic therapy with rescue PCI was associated with significantly lower rates of coronary patency and TIMI flow grade 3, but with significantly higher rates of mortality, death/MI and hemorrhagic complications at 30 days, as compared with primary PCI in this group of Chinese STEMI patients with late presentation and delayed treatments.     

Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment: the ISAR-REACT 2 randomized trial

Context  No specifically designed studies have addressed the role of the glycoprotein IIb/IIIa inhibitor abciximab in patients with non–ST-segment elevation acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) after pretreatment with 600 mg of clopidogrel. Objective  To assess whether abciximab is associated with clinical benefit in high-risk patients with ACS undergoing PCI after pretreatment with 600 mg of clopidogrel. Design, Setting, and Patients  International, multicenter, randomized, double-blind, placebo-controlled study conducted from March 2003 through December 2005, enrolling 2022 patients (mean age, 66 years) with non–ST-segment elevation ACS undergoing PCI. Interventions  Patients were assigned to receive either abciximab (0.25 mg/kg of body weight bolus, followed by a 0.125-µg/kg per minute [maximum, 10 µg/min] infusion for 12 hours, plus heparin, 70 U/kg of body weight) or placebo (placebo bolus and infusion of 12 hours, plus heparin bolus, 140 U/kg). All patients received clopidogrel, 600 mg, at least 2 hours prior to the procedure, as well as 500 mg of oral or intravenous aspirin. Main Outcome Measures  The primary end point was a composite of death, myocardial infarction, or urgent target vessel revascularization occurring within 30 days after randomization; secondary end points were rates of in-hospital major and minor bleeding. Results  Of 2022 patients enrolled, 1012 were assigned to abciximab and 1010 to placebo. The primary end point was reached in 90 patients (8.9%) assigned to abciximab vs 120 patients (11.9%) assigned to placebo, a 25% reduction in risk with abciximab (relative risk [RR], 0.75; 95% CI, 0.58-0.97; P = .03). Among patients without an elevated troponin level, there was no difference in the incidence of primary end point events between the abciximab group (23/499 patients [4.6%]) and the placebo group (22/474 patients [4.6%]) (RR, 0.99; 95% CI, 0.56-1.76; P = .98), whereas among patients with an elevated troponin level, the incidence of events was significantly lower in the abciximab group (67/513 patients [13.1%]) compared with the placebo group (98/536 patients [18.3%]), which corresponds to an RR of 0.71 (95% CI, 0.54-0.95; P = .02) (P = .07 for interaction). There were no significant differences between the 2 groups regarding the risk of major and minor bleeding as well as need for transfusion. Conclusions  Abciximab reduces the risk of adverse events in patients with non–ST-segment elevation ACS undergoing PCI after pretreatment with 600 mg of clopidogrel. The benefits provided by abciximab appear to be confined to patients presenting with an elevated troponin level. Trial Registration  ClinicalTrials.gov Identifier: NCT00133003      

Coagulation, inflammation and myocardial dysfunction in unstable coronary artery disease and the influence of glycoprotein IIb/IIIa inhibition and low molecular weight heparin

Patients with unstable coronary artery disease (CAD) have an increased risk of subsequent myocardial infarction and death. This study evaluated the safety and efficacy of treatment with glycoprotein IIb/IIIa inhibition in addition to aspirin, low molecular-weight heparin and its influence on coagulation and inflammation. Also, early and differentiated risk assessment utilising markers of inflammation, myocardial damage and dysfunction were evaluated. The Global Utilisation of Strategies To open Occluded arteries-IV (GUSTO-IV) trial randomised 7800 patients with unstable CAD to 24 or 48 hours infusion of abciximab or placebo in addition to routine treatment with aspirin and heparin or dalteparin. Baseline levels of creatinine, C-reactive protein (CRP), troponin T (TnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were analysed. At selected sites, all patients received subcutaneous dalteparin (n=974), in stead of heparin infusion (n=6826). In a sub-population of dalteparin treated patients (n=404), serial measurements of markers of coagulation, fibrinolysis and inflammation were also performed. Addition of abciximab to dalteparin as the primary treatment of unstable CAD was not associated with any significant reduction in cardiac events but a doubled risk of bleedings. The combination of abciximab with dalteparin seemed as safe when used with heparin. Despite full dose dalteparin and aspirin there was a simultaneous activation of the inflammation, coagulation and fibrinolysis systems without any influence of the abciximab treatment. Elevated levels of CRP, TnT, and NT-proBNP and reduced creatinine clearance were independently related to short and long-term mortality. The best prediction of high and low risk was provided by a combination of NT-proBNP and creatinine clearance. Any detectable elevation of TnT and reduced creatinine clearance, but neither elevation of CRP nor NT-proBNP, were also independently associated to a raised risk of subsequent myocardial infarction.     

Distal microcirculatory protection during percutaneous coronary intervention in acute ST-segment elevation myocardial infarction: a randomized controlled trial

Context  Atheromatous and thrombotic embolization during percutaneous coronary intervention (PCI) in acute myocardial infarction is common and may result in microcirculatory dysfunction, the prevention of which may improve reperfusion success, reduce infarct size, and enhance event-free survival. Objective  To determine whether protection of the distal microcirculation from thromboembolic debris liberated during primary PCI results in improved reperfusion and decreased infarct size. Design, Setting, and Patients  Prospective randomized controlled trial at 38 academic and community-based institutions in 7 countries enrolling 501 patients aged 18 years or older with ST-segment elevation myocardial infarction (STEMI) presenting within 6 hours of symptom onset and undergoing primary PCI or rescue intervention after failed thrombolysis. Interventions  Patients were randomized between May 20, 2002, and November 21, 2003, to receive PCI with a balloon occlusion and aspiration distal microcirculatory protection system vs angioplasty without distal protection. Main Outcome Measures  Coprimary end points were ST-segment resolution (STR) measured 30 minutes after PCI by continuous Holter monitoring and infarct size measured by technetium Tc 99m sestamibi imaging between days 5 and 14. Secondary end points included major adverse cardiac events. Results  Among 252 patients assigned to distal protection, aspiration was performed in 97% (242/251), all angioplasty balloon inflations were fully protected in 79% (193/245), and visible debris was retrieved from 73% (182/250). Complete STR was achieved in a similar proportion reperfused with vs without distal protection (63.3% [152/240] vs 61.9% [148/239], respectively; absolute difference, 1.4% [95% confidence interval, –7.7% to 10.5%; P = .78]), and left ventricular infarct size was similar in both groups (median, 12.0% [n = 229] vs 9.5% [n = 208], respectively; P = .15). Major adverse cardiac events at 6 months occurred with similar frequency in the distal protection and control groups (10.0% vs 11.0%, respectively; P = .66). Conclusions  A distal balloon occlusion and aspiration system effectively retrieves embolic debris in most patients with acute STEMI undergoing emergent PCI. Nonetheless, distal embolic protection did not result in improved microvascular flow, greater reperfusion success, reduced infarct size, or enhanced event-free survival.      

Mortality at 1 year with combination platelet glycoprotein IIb/IIIa inhibition and reduced-dose fibrinolytic therapy vs conventional fibrinolytic therapy for acute myocardial infarction: GUSTO V randomized trial

Context  Among patients with acute myocardial infarction, combination reperfusion therapy with a platelet glycoprotein IIb/IIIa receptor inhibitor (abciximab) and a half dose of a plasminogen activator (reteplase) did not significantly reduce mortality at 30 days compared with a full dose of reteplase. Rates of nonfatal ischemic complications were significantly diminished. Objective  To determine if the beneficial effects of abciximab and reteplase (combination therapy) on early nonfatal complications would translate into a reduction in the risk of death by 1 year. Design, Setting, and Patients  One-year follow-up of a randomized controlled trial (Global Use of Strategies To Open Coronary Arteries [GUSTO] V). Of 16 588 patients who had been treated in 820 community and referral hospitals in 20 countries between July 1999 and February 2001, mortality data were available for 16 453 (99.2%). Intervention  Patients were randomly assigned to receive (intravenously) a standard dose of reteplase (two 10-U boluses, 30 minutes apart) or the combination of a standard dose of abciximab (0.25 mg/kg bolus, 0.125 µg/kg per minute infusion [maximum 10 µg/min for 12 hours]) and a half dose of reteplase (two 5-U boluses, 30 minutes apart). Main Outcome Measure  One-year all-cause mortality rates. Results  All-cause mortality at 1 year occurred in 692 (8.38%) of 8260 patients in the reteplase group and 698 (8.38%) of the 8328 patients in the combination therapy group (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.90-1.11; P>.99). Reinfarction within the first 7 days occurred in 3.5% of patients in the reteplase group and 2.3% of patients in the combination therapy group, and was significantly associated with 1-year mortality (22.6% in patients with reinfarction vs 8.0% in patients without reinfarction; HR, 3.08; 95% CI, 2.53-3.75; P<.001). However, treatment assignment did not significantly influence time of mortality regardless of reinfarction status. Conclusion  Combination therapy (abciximab and reteplase) did not reduce mortality over 1 year compared with fibrinolytic therapy with reteplase alone.      

Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial

Context  Following percutaneous coronary intervention (PCI), short-term clopidogrel therapy in addition to aspirin leads to greater protection from thrombotic complications than aspirin alone. However, the optimal duration of combination oral antiplatelet therapy is unknown. Also, although current clinical data suggest a benefit for beginning therapy with a clopidogrel loading dose prior to PCI, the practical application of this therapy has not been prospectively studied. Objectives  To evaluate the benefit of long-term (12-month) treatment with clopidogrel after PCI and to determine the benefit of initiating clopidogrel with a preprocedure loading dose, both in addition to aspirin therapy. Design, Setting, and Participants  The Clopidogrel for the Reduction of Events During Observation (CREDO) trial, a randomized, double-blind, placebo-controlled trial conducted among 2116 patients who were to undergo elective PCI or were deemed at high likelihood of undergoing PCI, enrolled at 99 centers in North America from June 1999 through April 2001. Interventions  Patients were randomly assigned to receive a 300-mg clopidogrel loading dose (n = 1053) or placebo (n = 1063) 3 to 24 hours before PCI. Thereafter, all patients received clopidogrel, 75 mg/d, through day 28. From day 29 through 12 months, patients in the loading-dose group received clopidogrel, 75 mg/d, and those in the control group received placebo. Both groups received aspirin throughout the study. Main Outcome Measures  One-year incidence of the composite of death, myocardial infarction (MI), or stroke in the intent-to-treat population; 28-day incidence of the composite of death, MI, or urgent target vessel revascularization in the per-protocol population. Results  At 1 year, long-term clopidogrel therapy was associated with a 26.9% relative reduction in the combined risk of death, MI, or stroke (95% confidence interval [CI], 3.9%-44.4%; P = .02; absolute reduction, 3%). Clopidogrel pretreatment did not significantly reduce the combined risk of death, MI, or urgent target vessel revascularization at 28 days (reduction, 18.5%; 95% CI, -14.2% to 41.8%; P = .23). However, in a prespecified subgroup analysis, patients who received clopidogrel at least 6 hours before PCI experienced a relative risk reduction of 38.6% (95% CI, -1.6% to 62.9%; P = .051) for this end point compared with no reduction with treatment less than 6 hours before PCI. Risk of major bleeding at 1 year increased, but not significantly (8.8% with clopidogrel vs 6.7% with placebo; P = .07). Conclusions  Following PCI, long-term (1-year) clopidogrel therapy significantly reduced the risk of adverse ischemic events. A loading dose of clopidogrel given at least 3 hours before the procedure did not reduce events at 28 days, but subgroup analyses suggest that longer intervals between the loading dose and PCI may reduce events.      

比伐芦定与肝素对经皮冠状动脉介入急性心肌梗死患者抗凝效果的比较

目的 分析急性心肌梗死(AMI)患者经皮冠状动脉介入术(PCI)后使用比伐芦定与肝素的临床效果.方法 回顾性分析2018年1月至2020年1月于海南省人民医院急救中心就诊并接受PCI治疗的160例AMI患者的临床资料,其中80例患者在PCI后接受比伐芦定治疗(比伐芦定组),80例患者在PCI后接受肝素治疗(肝素组),比...     

Terminal complement blockade with pexelizumab during coronary artery bypass graft surgery requiring cardiopulmonary bypass: a randomized trial

Context  Inflammation and ischemia-reperfusion injury during coronary artery bypass graft (CABG) surgery requiring cardiopulmonary bypass are associated with postoperative myocardial infarction (MI) and mortality. Objective  To determine the efficacy and safety of pexelizumab, a C5 complement inhibitor, in reducing perioperative MI and mortality in CABG surgery. Design, Setting, and Participants  A randomized, double-blind, placebo-controlled trial, including 3099 patients (=" BORDER="0"> 18 years) undergoing CABG surgery with or without valve surgery at 205 hospitals in North America and Western Europe from January 2002 to February 2003. Interventions  Patients were randomly assigned to receive intravenous pexelizumab (2.0 mg/kg bolus plus 0.05 mg/kg per hour for 24 hours; n = 1553) or placebo (n = 1546) 10 minutes before undergoing the procedure. Main Outcome Measures  The primary composite end point was the incidence of death or MI within 30 days of randomization in those undergoing CABG surgery only (n = 2746). Secondary analyses included the intent-to-treat analyses of death or MI composite at days 4 and 30 in all 3099 study patients. Results  After 30 days, 134 (9.8%) of 1373 of patients receiving pexelizumab vs 161 (11.8%) of 1359 of patients receiving placebo (relative risk, 0.82; 95% confidence interval, 0.66-1.02; P = .07) died or experienced MI in the CABG surgery only population. In the intent-to-treat analyses, 178 (11.5%) of 1547 patients receiving pexelizumab vs 215 (14.0%) of 1535 receiving placebo died or experienced MI (relative risk, 0.82; 95% confidence interval, 0.68-0.99; P = .03). The trial was not powered to detect a reduction in mortality alone. Conclusions  Compared with placebo, pexelizumab was not associated with a significant reduction in the risk of the composite end point of death or MI in 2746 patients who had undergone CABG surgery only but was associated with a statistically significant risk reduction 30 days after the procedure among all 3099 patients undergoing CABG with or without valve surgery.      

Fluvastatin for prevention of cardiac events following successful first percutaneous coronary intervention: a randomized controlled trial

Context  Percutaneous coronary intervention (PCI) is associated with excellent short-term improvements in ischemic symptoms, yet only three fifths of PCI patients at 5 years and one third of patients at 10 years remain free of major adverse cardiac events (MACE). Objective  To determine whether treatment with fluvastatin reduces MACE in patients who have undergone PCI. Design and Setting  Randomized, double-blind, placebo-controlled trial conducted at 77 referral centers in Europe, Canada, and Brazil. Patients  A total of 1677 patients (aged 18-80 years) recruited between April 1996 and October 1998 with stable or unstable angina or silent ischemia following successful completion of their first PCI who had baseline total cholesterol levels between 135 and 270 mg/dL (3.5-7.0 mmol/L), with fasting triglyceride levels of less than 400 mg/dL (4.5 mmol/L). Interventions  Patients were randomly assigned to receive treatment with fluvastatin, 80 mg/d (n = 844), or matching placebo (n = 833) at hospital discharge for 3 to 4 years. Main Outcome Measure  Survival time free of MACE, defined as cardiac death, nonfatal myocardial infarction, or reintervention procedure, compared between the treatment and placebo groups. Results  Median time between PCI and first dose of study medication was 2.0 days, and median follow-up was 3.9 years. MACE-free survival time was significantly longer in the fluvastatin group (P = .01). One hundred eighty-one (21.4%) of 844 patients in the fluvastatin group and 222 (26.7%) of 833 patients in the placebo group had at least 1 MACE (relative risk [RR], 0.78; 95% confidence interval [CI], 0.64-0.95; P = .01). This result was independent of baseline total cholesterol levels (above [RR, 0.76; 95% CI, 0.56-1.04] vs below [RR, 0.77; 95% CI, 0.57-1.02] the median). In subgroup analysis, the risk of MACE was reduced in patients with diabetes (n = 202; RR, 0.53; 95% CI, 0.29-0.97; P = .04) and in those with multivessel disease (n = 614; RR, 0.66; 95% CI, 0.48-0.91; P = .01) who received fluvastatin compared with those who received placebo. There were no instances of creatine phosphokinase elevations 10 or more times the upper limit of normal or rhabdomyolysis in the fluvastatin group. Conclusion  Fluvastatin treatment in patients with average cholesterol levels undergoing their first successful PCI significantly reduces the risk of major adverse cardiac events.      

Pexelizumab for acute ST-elevation myocardial infarction in patients undergoing primary percutaneous coronary intervention: a randomized controlled trial

Context  Reperfusion with percutaneous transluminal coronary intervention (PCI) is effective at improving outcomes in patients with acute ST-elevation myocardial infarction (STEMI). However, in patients without prompt reestablishment of brisk coronary flow and tissue perfusion, mortality remains high, providing an opportunity for novel treatments, including anti-inflammatory agents. Objective  To evaluate the effectiveness of pexelizumab, a humanized monoclonal antibody that binds the C5 component of complement, as an adjunct to PCI in improving 30-day mortality from STEMI. Design, Setting, and Patients  This trial was a prospective, multicenter, double-blind, placebo-controlled, phase 3 study of the intravenous administration of pexelizumab in conjunction with primary PCI in STEMI with prespecified high-risk electrocardiographic findings. The trial was intended to enroll 8500 patients, but in conjunction with the US Food and Drug Administration enrollment was modified to 5745 patients presenting from 296 hospitals in 17 countries from July 13, 2004, to May 11, 2006. Interventions  Two thousand eight hundred eighty-five patients were randomly assigned to receive placebo and 2860 to receive pexelizumab given as a 2-mg/kg intravenous bolus prior to PCI followed by 0.05-mg/kg per hour infusion over the subsequent 24 hours. Patients were randomized within 6 hours of symptom onset. Main Outcome Measures  The primary end point was all-cause mortality through day 30. Secondary end points were death through day 90 and the composite of death, cardiogenic shock, or congestive heart failure through days 30 and 90. Results  No difference in mortality through day 30 was observed between the pexelizumab and placebo treatment groups, with 116 patients (4.06%) and 113 patients (3.92%) who died in the respective groups (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.80-1.35; log-rank P = .78). The composite end points of death, shock, or heart failure were also similar with 257 patients (8.99%) receiving pexelizumab and 265 patients (9.19%) receiving placebo at 30 days (HR, 0.98; 95% CI, 0.83-1.16; P = .81) and 293 patients (10.24%) receiving pexelizumab and 293 patients (10.16%) receiving placebo at 90 days (HR, 1.01; 95% CI, 0.86-1.19; P = .91). Conclusion  In this large clinical trial of patients treated with primary PCI for STEMI, mortality was low and unaffected by administration of pexelizumab. Trial Registration  clinicaltrials.gov Identifier: NCT00091637      

红花注射液对急性冠状动脉综合征患者血小板糖蛋白Ⅱb／Ⅲa受体影响的随机对照研究

背景：血小板表面糖蛋白（glycoprotein,GP）Ⅱb／Ⅲa受体是评价血小板活化的重要指标,具有活血化瘀作用的中成药红花注射液对该指标的影响对于探讨其抗血小板凝集作用机制及疗效有重要意义。目的：观察红花注射液对急性冠状动脉综合征患者血小板表面糖蛋白GPⅡb／Ⅲa受体的影响,探讨红花注射液在抗血小板凝集治疗中的作用及其机制。设计、场所、对象和干预措施：选择2008年9月至2009年5月在上海中医药大学附属岳阳中西医结合医院心血管内科住院的急性冠状动脉综合征患者64例,用随机数字表法分为红花注射液治疗组（32例,常规西药加红花注射液）与对照组（32例,常规西药）,两组疗程均为14d。主要结局指标：采用免疫荧光标记法和流式细胞仪检测治疗前后血小板活化标志物GPⅡb／Ⅲa复合物（CD41）、P选择素（CD62p）和溶酶体膜糖蛋白（CD63）的表达,同时观察红花注射液对急性冠状动脉综合征患者心绞痛症状及近期预后的影响。结果：对照组中有4例患者因提前出院而退出试验。对照组和治疗组的CD41比例、CD41抗体荧光量治疗后比治疗前均有所降低,差异有统计学意义（P〈0．05,P〈0．01）;治疗后治疗组CD41比例、CD41抗体荧光量低于对照组（P〈0．05）;两组CD62p比例和CD63比例治疗后均呈现出一定的下降趋势,但与治疗前比较差异无统计学意义。两组患者在住院14d中均未发生死亡、心肌梗死、脑卒中事件,红花注射液治疗组患者心绞痛症状缓解和心电图表现均明显好于对照组。结论：红花注射液具有抑制血小板膜糖蛋白GPⅡb／Ⅲa受体表达的作用,对急性冠状动脉综合征患者心绞痛具有很好的缓解作用,可增强常规西药抗血小板活化的作用。