Outcomes of Patients with Coronary Artery Perforation Complicating Percutaneous Coronary Intervention and Correlations with the Type of Adjunctive Antithrombotic Therapy: Pooled Analysis from REPLACE-2, ACUITY, and HORIZONS-AMI Trials

Background: The lack of a specific counteragent to bivalirudin may complicate the management of patients with coronary artery (CA) perforation during percutaneous coronary intervention (PCI).
Aim: Assess outcomes of patients with CA perforation from three PCI trials comparing intravenous bivalirudin with provisional glycoprotein (GP) IIb/IIIa inhibition versus unfractionated heparin (UFH) plus GP IIb/IIIa.
Methods: A pooled analysis of patients treated with PCI in three randomized trials including REPLACE-2, ACUITY, and HORIZONS-AMI.
Results: Among a total of 12,921 patients, CA perforation occurred in 35 patients (0.27%). By multivariable analysis, baseline creatinine clearance was the only independent predictor of CA perforation (per 10 mL/min decrease, odds ratio [95% confidence interval]= 1.28 [1.11, 1.47], P = 0.0007). At 30 days, patients with versus without CA perforation had significantly (all P values ≤0.001) higher rates of 30-day mortality (11.4% vs. 1.0%), myocardial infarction (MI) [Q wave: 22.9% vs. 5.7%; non-Q wave: 17.1% vs. 4.9%], target vessel revascularization (TVR) [20.1% vs. 1.8%], and composite end-point of death/MI/TVR (31.4% vs. 7.8%). Patients assigned to bivalirudin versus UFH plus a GP IIb/IIIa inhibitor had nonsignificantly lower rates of death (0% vs. 18.8%, P = 0.08), similar rates of MI (26.7% vs. 25.0%, P = 0.92), significantly lower rates of TVR (6.7% vs. 37.5%, P = 0.04), and similar rates of the composite end-point of death/MI/TVR (35.5% vs. 26.7%, P = 0.54).
Conclusion: In three PCI trials, treatment of patients experiencing CA perforation with adjunctive antithrombotic therapy of bivalirudin monotherapy was not associated with worse outcomes compared to treatment with UFH plus GP IIb/IIIa inhibitors.     

Efficacy and safety of bivalirudin in patients receiving clopidogrel therapy after diagnostic angiography for percutaneous coronary intervention in acute coronary syndromes

Objectives : This study sought to investigate if the efficacy of bivalirudin monotherapy is similar to heparin plus GP IIb/IIIa inhibition in patients with acute coronary syndromes (ACS) treated with clopidogrel following diagnostic angiography. Background : Prior trials have demonstrated that peri‐procedural bivalirudin therapy confers similar efficacy as heparin plus GP IIb/IIIa inhibitors, while lowering the risk of bleeding complications in ACS patients undergoing percutaneous coronary intervnetions (PCI). However, the incidence of adverse ischemic events post‐PCI appeared to be higher in patients receiving bivalirudin without adequate pretreatment with clopidogrel. Methods : Using the 2004/2005 Cornell Angioplasty Registry, we evaluated 980 consecutive patients undergoing urgent PCI for UA/NSTEMI who were treated with either bivalirudin or UFH plus GP IIb/IIIa inhibitor. We excluded patients who were on chronic clopidogrel therapy or received clopidogrel pretreatment prior to angiography. All patients received a clopidogrel load (≥300‐mg dose) immediately before or after the PCI. Long‐term all‐cause mortality was obtained for 100% of patients, with a mean follow‐up of 24.6 ± 7.7 months. Results : Of the 980 study patients, 461 (47.0%) were treated with bivalirudin and 519 (53.0%) patients received UFH plus GP IIb/IIIa inhibitor. DES were used in 88% of PCI; 45% of patients presented with NSTEMI. The incidence of in‐hospital death (0.4% vs. 0.2%, P = 0.604), post‐procedural MI (6.9% vs. 5.4%, P = 0.351), and MACE including death, stroke, emergent CABG/PCI, and MI (7.6% vs. 5.8%, P = 0.304) were similar in patients treated with bivalirudin versus UFH plus GP IIb/IIIa inhibitors, respectively. The incidence of in‐hospital stent thrombosis was similar (0.7% vs. 0%, P = 0.104), while major (0.9% vs. 2.9%, P = 0.034) and minor bleeding (10.4% vs. 18.9%, P < 0.001) was reduced in the bivalirudin‐treated group. By two‐years of follow‐up, after propensity‐score adjusted multivariate Cox regression analysis, there was no significant difference in long‐term mortality between the two groups (HR 1.18; 95%CI 0.64–2.19, P = 0.598). Conclusions : In patients presenting with ACS and receiving clopidogrel treatment after angiography (before or within 30 min of PCI), peri‐procedural bivalirudin monotherapy suppresses acute and long‐term adverse events to a similar extent as does UFH plus GP IIb/IIIa inhibitors, while significantly lowering the risk of bleeding complications. © 2010 Wiley‐Liss, Inc.     

Triple antiplatelet therapy during percutaneous coronary intervention is associated with improved outcomes including one-year survival: results from the Do Tirofiban and ReoProGive Similar Efficacy Outcome Trial (TARGET)

OBJECTIVE: We sought to examine if clopidogrel treatment initiated before coronary stenting improved clinical outcomes among patients receiving aspirin and a glycoprotein (GP) IIb/IIIa inhibitor. BACKGROUND: Antiplatelet therapy plays a pivotal role in contemporary percutaneous coronary interventions (PCI). METHODS: Outcomes among 4,809 patients randomized to tirofiban or abciximab during PCI with stent placement were compared according to whether they received 300 mg of clopidogrel before PCI (93.1%) versus immediately after the procedure. RESULTS: The 30-day primary composite end point (death, myocardial infarction [MI], or urgent target vessel revascularization [TVR]) was lower among clopidogrel-pretreated patients (6.6% vs. 10.4%, p = 0.009), mainly because of reduction of MI (6.0% vs. 9.5%, p = 0.012). The benefit of clopidogrel pretreatment was sustained at six months (death, MI, any TVR: 14.6% vs. 19.8%, HR = 0.71, p = 0.010), and this was due mainly to lowering of death and MI (7.8% vs. 13.0%, p = 0.001). At one year, clopidogrel pretreatment was associated with a lower mortality rate (1.7% vs. 3.6%, p = 0.011). Because clopidogrel pretreatment was not randomized, multivariable and propensity analyses were performed. After adjusting for baseline heterogeneity, clopidogrel pretreatment was an independent predictor for death or MI at 30 days (HR = 0.63, p = 0.012) and at six months (HR = 0.61, p = 0.003), and survival at one year (HR = 0.53, p = 0.044). No excess in 30-day bleeding events was noted with clopidogrel pretreatment. CONCLUSIONS: Among patients undergoing coronary stent placement with aspirin and a GP IIb/IIIa inhibitor, clopidogrel pretreatment is associated with a reduction of death and MI irrespective of the type of GP IIb/IIIa inhibitor used.     

Stenting and glycoprotein IIb/IIIa inhibition in patients with acute myocardial infarction undergoing percutaneous coronary intervention: findings from the global registry of acute coronary events (GRACE).

Stenting and GP IIb/IIIa inhibition are promising adjunctive therapies in PCI. The Global Registry of Acute Coronary Events (GRACE) is a registry of unselected patients with acute coronary syndromes, allowing for the study of treatments in a real-world environment. Data from GRACE patients with AMI who underwent PCI were analyzed. After adjusting for demographics, baseline characteristics, and previous medications, treatment with GP IIb/IIIa inhibitors and a stent and treatment with a stent alone were significant predictors of survival at 6 months. Stents were used in 90.9% of patients. GP IIb/IIIa inhibitors were used in 59.7%; in most cases they were started after the beginning of the procedure. The in-hospital death rate (7.6%) was highest in patients undergoing urgent PCI. Mortality at 6 months following PCI was 14.4% among patients who received neither GP IIb/IIIa inhibitors nor a stent, compared to patients who received both GP IIb/IIIa inhibitors and a stent (7.3%), GP IIb/IIIa inhibitors alone (12.8%), or a stent alone (6.7%).     

Effect of body mass index on Argatroban therapy during percutaneous coronary intervention

BACKGROUND: Obesity is common in patients undergoing percutaneous coronary intervention (PCI). Argatroban, a direct thrombin inhibitor, is used during PCI in patients with or at risk of heparin-induced thrombocytopenia (HIT) and also has been evaluated in conjunction with glycoprotein IIb/IIIa inhibition in nonHIT patients. We investigated the effect of body mass index (BMI), and specifically obesity (BMI>30 kg/m2), on argatroban therapy during PCI. METHODS: From previously reported studies of argatroban therapy during PCI in patients with or at risk of HIT (ie, HIT group) or in conjunction with glycoprotein IIb/IIIa inhibition (ie, nonHIT group), we identified patients with sufficient data to determine BMI. After an initial bolus of 350 microg/kg (HIT group) or 300 or 250 microg/kg (nonHIT group), patients received continuous argatroban 25-30 microg/kg/min (adjusted to achieve ACTs of 300-450 s, HIT group) or 15 microg/kg/min (target ACTs of 275-325 s, nonHIT group) during PCI, with additional 150 microg/kg boluses allowed if needed. Regression analyses evaluated relationships between patient BMI and ACT response to initial bolus administration, mean infusion dose (HIT group only), and rate of ACT decline after PCI. Frequencies of additional bolus usage and clinical outcomes were compared between obese and nonobese patients. RESULTS: Our analysis population included 225 patients (85 obese) in total: 73 in the HIT group and 152 in the nonHIT group (300 microg/kg bolus, n=101; 250 microg/kg bolus, n=51), with BMIs of 16.3-50.9 kg/m2. No association was detected between BMI and the first ACT after bolus administration (median ACTs of 361, 298, and 289 s, respectively, following 350, 300, and 250 microg/kg bolus), mean infusion dose (24.2+/-4.9 microg/kg/min overall in HIT group), or time to ACTsor=0.35). Clinical outcomes did not differ (P>or=0.09) between obese and nonobese individuals: 4 (3 obese) patients in the HIT group and 4 (2 obese) in the nonHIT group had ischemic complications; 1 nonobese patient in the HIT group and 2 (1 obese) in the nonHIT group experienced major bleeding. CONCLUSIONS: These findings support the use of actual body weight-adjusted (and ACT-targeted) argatroban therapy during PCI and suggest that dose adjustment for obesity (BMI up to 50.9 kg/m2) is unnecessary.     

Association of glycoprotein IIb/IIIa inhibitors and long-term survival following administration during percutaneous coronary intervention for acute myocardial infarction

Objectives: We sought to evaluate the impact of GP IIb/IIIa receptor blockers on long-term mortality in patients undergoing PCI for AMI. Background: Glycoprotein (GP) IIb/IIIa inhibitors are potent suppressors of platelet aggregation and when used during percutaneous coronary intervention (PCI) for the treatment of acute myocardial infarction (AMI) may improve short-term clinical outcomes, including survival. However, the impact of GP IIb/IIIa treatment during PCI for AMI on long-term survival is unknown. Methods: Patients undergoing primary or rescue PCI for AMI within 24 hours of symptom onset with or without GP IIb/IIIa inhibitor treatment were identified from a multicenter PCI database. All cause mortality at a mean follow-up of 3 years was the primary end point. Results: Of the 269 patients treated with primary or rescue PCI for AMI, 107 (40%) received a GP IIb/IIIa antagonist. Patients treated with GP inhibitors were more likely to present with or develop heart failure (13% vs. 6.2%, P = 0.052). Left ventricular ejection fraction was reduced in those treated with GP IIb/IIIa antagonists (44% vs. 48%, P = 0.051). The extent of coronary artery disease did not differ between groups. Stent use was 80% in both groups. Procedural success was high and did not differ between groups. In-hospital mortality was low and did not differ between groups. The mortality at a mean follow-up of 3 years was 1.9% among patients treated with a GP IIb/IIIa antagonist and 15% for those who were not treated (log-rank P = 0.0005). Treatment with a GP IIb/IIIa antagonist was independently associated with a significant reduction in the hazard of long-term mortality (Hazard Ratio, 0.159; 95% Confidence Interval, 0.034–0.729; P = 0.018). Conclusions: Treatment of patients undergoing PCI for AMI with GP IIb/IIIa antagonists appears to be associated with a profound reduction in late mortality.     

Direct thrombin inhibition appears to be a safe and effective anticoagulant for percutaneous bypass graft interventions.

BACKGROUND: Percutaneous coronary interventions (PCI) of coronary artery bypass grafts (CABG) are associated with worse outcomes compared with those of native coronary PCI. Little is known concerning the use of direct thrombin inhibition during CABG intervention. The objective of this report is to examine the safety and efficacy of bivalirudin with GPIIb/IIIa blockade inhibition in patients undergoing CABG PCI. GP IIb/IIIa use was provisional in REPLACE-2 and planned in REPLACE-1. METHODS AND RESULTS: A post hoc analysis of patients undergoing CABG PCI in the REPLACE-1 and -2 trials was performed. In REPLACE-1, patients were randomized to either heparin or bivalirudin, with GP IIb/IIIa inhibitor use at the operator's discretion. In REPLACE-2, patients were randomized to heparin plus GP IIb/IIIa inhibition versus bivalirudin with provisional GP IIb/IIIa blockade. In both studies, randomized treatment groups were well matched. In unadjusted and logistic regression analysis, there were no significant differences in the combined endpoint of death, myocardial infarction, urgent revascularization, or major bleeding when patients were treated with either heparin or bivalirudin. Individual safety and efficacy endpoints were also similar. Minor bleeding was significantly reduced in patients treated with bivalirudin (14.8% vs. 22.7%, P = 0.037). Follow-up data available from the REPLACE-2 trial at 12 months found similar efficacy between groups with a trend towards decreased 12 month mortality in the bivalirudin vs. heparin groups (4.2% vs. 7.8%, P = 0.16). CONCLUSION: CABG PCI using bivalirudin with provisional GPIIb/IIIa inhibition appears to provide similar safety and efficacy to heparin with GPIIb/IIIa inhibition.     

Timing of glycoprotein IIb/IIIa inhibitor use and outcomes among patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention (results from CRUSADE)

Although glycoprotein (GP) IIb/IIIa inhibitors are recommended for patients with unstable angina and non-ST-segment elevation myocardial infarction who undergo percutaneous coronary intervention (PCI), the American College of Cardiology/American Heart Association guidelines do not specify optimal timing for their initiation. We compared patient characteristics and clinical outcomes in 30,830 patients with non-ST-segment elevation myocardial infarction included in the CRUSADE initiative (January 2001 to December 2004) who underwent PCI with upstream (>1 hour before PCI) or periprocedural use of GP IIb/IIIa inhibitors. GP IIb/IIIa inhibitors were administered upstream in 43% of patients versus periprocedurally in 57%. Time from arrival to PCI was longer for patients who received GP IIb/IIIa inhibitors upstream (median 25.6 hours) compared with periprocedurally (18.2 hours). Unadjusted incidence of in-hospital death or reinfarction was lower with upstream GP IIb/IIIa inhibitor use (3.8% vs 4.3%, p = 0.046), but after adjusting for patient and hospital characteristics, this difference was not statistically significant. Treatment with upstream GP IIb/IIIa inhibitors was associated with a lower incidence of unadjusted death or reinfarction in patients who underwent PCI <12 hours from hospital arrival. In conclusion, in this observational analysis, overall ischemic outcomes were similar between the 2 groups, but clinical trials are needed to solve the controversy over optional timing of GP IIb/IIIa inhibitor use.     

The impact of GP IIb/IIIa inhibitors during primary percutaneous coronary intervention in acute myocardial infarction patients

The use of glycoprotein (GP) IIb/IIIa inhibitors during percutaneous coronary interventions (PCI) in the acute phase of myocardial infarction (AMI) is still a matter of debate. The aim of the present study was to compare the outcomes of patients with acute ST-segment elevation myocardial infarction who underwent primary PCI and were concomitantly treated with GP IIb/IIIa inhibitors with those who were not treated with these drugs. Between January 1996 and November 2003, a total of 418 consecutive patients underwent PCI in the setting of ST-segment elevation AMI. At the operator's discretion, 287 patients were concomitantly treated with GP IIb/IIIa inhibitors and 115 patients were not. Angiographic success and final TIMI 3 flow in the infarct-related artery was achieved more frequently in patients treated with GP IIb/IIIa inhibitors (90% vs. 77%; p=0.001). The in-hospital composite endpoint of death, reinfarction and bleeding complications was significantly better in patients treated with GP IIb/IIIa inhibitors (4% vs. 12%; p=0.005). Furthermore, the adjusted 12-month survival rate was significantly better in these patients (RR: 2.99, CI: 1.29-6.9; p=0.01). Therefore, adjunctive therapy with GP IIbIIIa inhibitors during primary PCI is associated with improved short-term outcomes and one-year survival without an increased risk of bleeding.     

Economic evaluation of bivalirudin with provisional glycoprotein IIB/IIIA inhibition versus heparin with routine glycoprotein IIB/IIIA inhibition for percutaneous coronary intervention: results from the REPLACE-2 trial

OBJECTIVES: The purpose of this study was to compare the cost of percutaneous coronary intervention (PCI) using bivalirudin with provisional platelet glycoprotein (GP) IIb/IIIa inhibition with that of heparin + routine GP IIb/IIIa inhibition. BACKGROUND: Although GP IIb/IIIa inhibition has been shown to reduce ischemic complications in a broad range of patients undergoing PCI, many patients currently do not receive such therapy because of concerns about bleeding complications or cost. Recently, bivalirudin with provisional GP IIb/IIIa inhibition has been validated as an alternative to heparin + routine GP IIb/IIIa inhibition for patients undergoing PCI. However, the cost-effectiveness of this novel strategy is unknown. METHODS: In the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial, 4,651 U.S. patients undergoing non-emergent PCI were randomized to receive bivalirudin with provisional GP IIb/IIIa (n = 2,319) versus heparin + routine GP IIb/IIIa (n = 2,332). Resource utilization data were collected prospectively through 30-day follow-up on all U.S. patients. Medical care costs were estimated using standard methods including bottom-up accounting (for procedural costs), the Medicare fee schedule (for physician services), hospital billing data (for 2,821 of 4,862 admissions), and regression-based approaches for the remaining hospitalizations. RESULTS: Among the bivalirudin group, 7.7% required provisional GP IIb/IIIa. Thirty-day ischemic outcomes including death or myocardial infarction were similar for the bivalirudin and GP IIb/IIIa groups, but bivalirudin resulted in lower rates of major bleeding (2.8% vs. 4.5%, p = 0.002) and minor bleeding (15.1% vs. 28.1%, p < 0.001). Compared with routine GP IIb/IIIa, in-hospital and 30-day costs were reduced by $405 (95% confidence interval [CI] $37 to $773) and $374 (95% CI $61 to $688) per patient with bivalirudin (p < 0.001 for both). Regression modeling demonstrated that, in addition to the costs of the anticoagulants themselves, hospital savings were due primarily to reductions in major bleeding (cost savings = $107/patient), minor bleeding ($52/patient), and thrombocytopenia ($47/patient). CONCLUSIONS: Compared with heparin + routine GP IIb/IIIa inhibition, bivalirudin + provisional GP IIb/IIIa inhibition resulted in similar acute ischemic events and cost savings of $375 to $400/patient depending on the analytic perspective.     

Comparison of bivalirudin versus heparin plus glycoprotein IIb/IIIa inhibitors in patients undergoing an invasive strategy: A meta-analysis of randomized clinical trials

Objective

This meta-analysis was performed to assess the efficacy and safety of bivalirudin compared with unfractionated heparin or enoxaparin plus glycoprotein (GP) IIb/IIIa inhibitors in patients undergoing percutaneous coronary intervention (PCI).

Background

Pharmacotherapy for patients undergoing PCI includes bivalirudin, heparin, and GP IIb/IIIa inhibitors. We sought to compare ischemic and bleeding outcomes with bivalirudin versus heparin plus GP IIb/IIIa inhibitors in patients undergoing PCI.

Methods

A literature search was conducted to identify fully published randomized trials that compared bivalirudin with heparin plus GP IIb/IIIa inhibitors in patients undergoing PCI.

Results

A total of 19,772 patients in 5 clinical trials were included in the analysis (9785 patients received bivalirudin and 9987 patients received heparin plus GP IIb/IIIa inhibitors during PCI). Anticoagulation with bivalirudin, as compared with heparin plus glycoprotein IIb/IIIa inhibitors, results in no difference in major adverse cardiovascular events (odds ratio [OR] 1.07, 95% confidence interval [CI] 0.96 to 1.19), death (OR 0.93, 95% CI 0.72 to 1.21), or urgent revascularization (OR 1.06, 95% CI 0.86 to 1.30). There is a trend towards a higher risk of myocardial infarction (OR 1.12, 95% CI 0.99 to 1.28) but a significantly lower risk of TIMI major bleeding with bivalirudin (OR 0.55, 95% CI 0.44 to 0.69).

Conclusion

In patients who undergo PCI, anticoagulation with bivalirudin as compared with unfractionated heparin or enoxaparin plus GP IIb/IIIa inhibitors results in similar ischemic adverse events but a reduction in major bleeding.     

Bivalirudin in PCI: an overview of the REPLACE-2 trial

The Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial is one of the largest acute randomized controlled trials evaluating the efficacy of two anticoagulant strategies during contemporary urgent or elective percutaneous coronary intervention (PCI). The direct thrombin inhibitor, bivalirudin, with provisional use of glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitor was compared to low-dose unfractionated heparin (UFH) plus planned GP IIb/IIIa inhibitor. At 30-day follow-up, the primary quadruple composite endpoint (death, myocardial infarction (MI), urgent repeat revascularization, or in-hospital major bleeding) occurred in 9.2% of patients in the bivalirudin group versus 10.0% of patients in the UFH plus GP IIb/IIIa inhibitor group. The secondary triple composite endpoint (death, MI, urgent repeat revascularization) occurred in 7.6% of patients in the bivalirudin group compared with 7.1% of patients in the UFH plus GP IIb/IIIa inhibitor group. Both endpoints met formal statistical criteria for noninferiority to UFH plus GP IIb/IIIa inhibitor. By imputed comparison from historic GP IIb/IIIa trials between bivalirudin versus UFH alone, REPLACE-2 demonstrated that bivalirudin was superior to UFH alone with respect to the quadruple and triple composite endpoints. Furthermore, bivalirudin plus provisional GP IIb/IIIa blockade was associated with a significant reduction in in-hospital bleeding (2.4% vs. 4.1%; p < 0.001). At 6 months' follow-up, there was no significant difference in rates of death, MI, or revascularization between the two groups. Furthermore, there was no evidence that the early, nonsignificant 0.5% excess non-Q-wave MI in the bivalirudin group translated into later mortality. There was a trend toward decreased mortality at 6 months in the bivalirudin arm (0.95% vs. 1.35%; p = 0.148). The relative efficacy of bivalirudin versus UFH plus GP IIb/IIIa inhibitor was similar in several high-risk subgroups, including patients with diabetes mellitus or prior MI, women, the elderly (age > 65 years), and patients undergoing PCI of bypass grafts. Bivalirudin represents an exciting alternative to UFH plus GP IIb/IIIa inhibitor in patients undergoing urgent and elective PCI with similar suppression of ischemic events, fewer bleeding complications, and the potential for greater cost savings and ease of administration.     

Glycoprotein IIb/IIIa inhibitors during rescue percutaneous coronary intervention in acute myocardial infarction

Although percutaneous coronary intervention (PCI) following full-dose thrombolytic therapy (rescue angioplasty) is a common procedure, there is ample controversy regarding the usefulness of the procedure. Moreover, few data are available concerning the safety and efficacy of concomitant treatment with glycoprotein (GP) IIb/IIIa inhibitors in these patients. The aim of the present study was to compare the clinical outcomes of patients who underwent rescue PCI with stents and were treated with GP IIb/IIIa inhibitors. A total of 59 consecutive patients underwent rescue PCI at our institution during the study period, 29 patients (49.2%) were treated concomitantly with a GP IIb/IIIa inhibitor and 30 patients (50.8%) were not. Baseline clinical characteristics were similar between the two groups. In-hospital outcomes regarding death, reinfarction and the need for urgent target vessel revascularization was significantly lower in patients treated with GP IIb/IIIa inhibitors compared to those who were not treated (3.4% vs. 26.7%; p = 0.01, respectively). However, GP IIb/IIIa inhibitor administration was not an independent predictor of better outcomes by multivariate analysis. There was a higher rate of major bleeding complications in patients who received GP IIb/IIIa inhibitors, though it did not achieve statistical significance (6.9% vs. 0%; p = 0.14, respectively). The composite endpoint of major, minor bleeding and vascular complications was similar in both groups (24.1% vs. 16.7%; p = 0.48). In conclusion, the administration of GP IIb/IIIa inhibitors in patients undergoing rescue PCI after failed thrombolysis with stents was safe and may have a beneficial effect on 30-day event-free survival rates, without a significant increase in bleeding or vascular complications. These results warrant further investigation.     

Is glycoprotein IIb/IIIa antagonism as effective in women as in men following percutaneous coronary intervention?. Lessons from the ESPRIT study

OBJECTIVE: The study was done to determine whether eptifibatide, a platelet glycoprotein (GP) IIb/IIIa antagonist, prevents ischemic complications following percutaneous coronary interventions (PCIs) in women as well as in men. BACKGROUND: Eptifibatide reduces ischemic complications after nonurgent coronary stent interventions. METHODS: We compared outcomes in women (n = 562) and men (n = 1,502) enrolled in the Enhanced Suppression of the Platelet GP IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial of double-bolus eptifibatide during PCI. RESULTS: Women in the ESPRIT trial were older, and more frequently had hypertension, diabetes mellitus, or acute coronary syndromes, but were less likely to have prior PCI or coronary artery bypass graft surgery. The primary end point, a composite at 48 h of death, myocardial infarction (MI), urgent target vessel revascularization (TVR), and unplanned GP IIb/IIIa use, occurred in 10.5% of women and 7.9% of men (p = 0.082). The composite of death, MI, or TVR after one year occurred in 24.5% of women compared with 18% of men (p = 0.0008). At 48 h, eptifibatide reduced the composite of death, MI, and TVR from 14.5% to 6.0% in women versus 9.0% to 6.8% in men. At one year, these differences persisted: 28.9% versus 20.0% for women and 19.5% versus 16.6% for men. No statistical interaction existed between treatment and gender at either 48 h (p = 0.063) or one year (p = 0.2). Bleeding occurred more commonly in women (5.5% vs. 2.6%, p = 0.002), and was more common in eptifibatide-treated women. After adjustment for age, weight, and hypertension, no interaction between treatment and gender was present. CONCLUSION: Eptifibatide is effective to prevent ischemic complications of PCI in women and may eliminate gender-related differences in PCI outcomes.     

Impact of body mass index on the five-year outcome of patients having percutaneous coronary interventions with drug-eluting stents

The purpose of this study was to assess the impact of body mass index (BMI) on clinical outcome of patients treated by percutaneous coronary intervention (PCI) using drug-eluting stents. Patients were stratified according to BMI as normal (<25 kg/m(2)), overweight (25 to 30 kg/m(2)), or obese (>30 kg/m(2)). At 5-year follow-up all-cause death, myocardial infarction, clinically justified target vessel revascularization (TVR), and definite stent thrombosis were assessed. A complete dataset was available in 7,427 patients, of which 45%, 22%, and 33% were classified according to BMI as overweight, obese, and normal, respectively. Mean age of patients was significantly older in those with a normal BMI (p <0.05). Incidence of diabetes mellitus, hypertension, and dyslipidemia increased as BMI increased (p <0.05). Significantly higher rates of TVR (15.3% vs 12.8%, p = 0.02) and early stent thrombosis (1.5% vs 0.9%, p = 0.04) were observed in the obese compared to the normal BMI group. No significant difference among the 3 BMI groups was observed for the composite of death/myocardial infarction/TVR or for definite stent thrombosis at 5 years, whereas the normal BMI group was at higher risk for all-cause death at 5 years (obese vs normal BMI, hazard ratio 0.74, confidence interval 0.53 to 0.99, p = 0.05; overweight vs normal BMI, hazard ratio 0.73, confidence interval 0.59 to 0.94, p = 0.01) in the multivariate Cox proportional hazard model. Age resulted in a linearly dependent covariate with BMI in the all-cause 5-year mortality multivariate model (p = 0.001). In conclusion, the "obesity paradox" observed in 5-year all-cause mortality could be explained by the higher rate of elderly patients in the normal BMI group and the existence of colinearity between BMI and age. However, obese patients had a higher rate of TVR and early stent thrombosis and a higher rate of other risk factors such as diabetes mellitus, hypertension, and hypercholesterolemia.     

Incidence and predictors of major vascular complications after percutaneous coronary intervention in the glycoprotein IIb/IIIa platelet inhibitor era

Since the introduction of platelet glycoprotein (GP) IIb/IIIa inhibitors, reports of vascular complications after percutaneous coronary intervention (PCI) have focused on bleeding and the need for surgical repair, whereas specific major vascular complications have been less consistently identified. Moreover, data from clinical trials may lack applicability to the general population. The purpose of this study was to determine the incidence of major vascular complications after PCI and to identify associated risk factors in patients routinely receiving GP IIb/IIIa inhibitors. During a 12-month period, 1,634 consecutive patients underwent PCI at a single institution. Clinical characteristics and procedural data were collected prospectively; data regarding vascular sheath removal were obtained retrospectively. Univariate and multivariable regression methods were used to identify independent predictors of major vascular complications. Major vascular complications occurred in 2.9% of patients. Multivariable analysis revealed advanced age (odds ratio [OR] 1.05, P = 0.0025) and female sex (OR 2.9, P = 0.0002) as clinical characteristics associated with major vascular complications, whereas hypertension had an inverse relationship (OR 0.46, P = 0.013). Procedural factors included use of the following: stents (OR 5.59, P < 0.0001), vascular sheaths >6F (OR 3.25, P = 0.016), and mechanical clamp (OR 2.71, P = 0.0012). The presence of a hematoma >4 cm(2) had a positive predictive value of 12% for major vascular complications. The incidence of major vascular complications in this large, single-center study from the GP IIb/IIIa inhibitor era is consistent with data from the pre-GP IIb/IIIa inhibitor era and recent randomized trials.     

盐酸替罗非班在ST段抬高急性心肌梗死急诊PCI中的安全性分析

目的:评价GPⅡb/Ⅲa受体拮抗剂盐酸替罗非班(商品名欣维宁)在ST段抬高急性心肌梗死(STEMI)急诊经皮冠状动脉腔内介入术(PCI)治疗中的安全性。方法:65例急诊入院STEMI行急诊PCI患者,分为试验组(盐酸替罗非班+PCI)36例和对照组(直接PCI29例)。观察2组住院期间主要心血管事件(MACE)包括死亡、新近心肌梗死和顽固缺血状态、术后左心室射血分数(LVEF)、压迫止血时间及不良反应(出血、血小板减少)。结果:住院期间主要心血管事件(majoradversecardiovascularevents,MACE)发生率,试验组低于对照组(5.6%比13.7%);术后LVEF(59.42±8.06比52.65±5.20)高于对照组;2组均未发生严重出血并发症(包括大量出血和颅内出血等),出血事件发生率试验组较对照组有增多的趋势(11.1%比3.4%),试验组部分凝血活酶时间(activatedpar_tialthromboplastintime,APTT)较对照组延长(58.15±11.86比33.78±11.28),(P<0.05);压迫止血时间明显延长(37.25±6.34比20.12±5.55),(P<0.05),但未增加穿刺点出血和血肿。结论:血小板GPⅡb/Ⅲa受体拮抗剂盐酸替罗非班联合PCI可能成为STEMI患者急诊PCI安全和有效的再灌注手段。     

Complementary effects of thienopyridine pretreatment and platelet glycoprotein IIb/IIIa integrin blockade with eptifibatide in coronary stent intervention; results from the ESPRIT trial.

OBJECTIVES: This analysis sought to investigate the complementary effect of thienopyridine pretreatment and platelet glycoprotein (GP) IIb/IIIa integrin blockade in coronary stent intervention. BACKGROUND: Definitive evidence supporting combined antiplatelet therapy consisting of thienopyridine pretreatment and GP IIb/IIIa receptor blockade in patients undergoing percutaneous coronary intervention (PCI) with stent implantation is limited. METHODS: We retrospectively analyzed clinical outcomes by thienopyridine use in the 2,040 patients randomized to eptifibatide or placebo who underwent PCI in the ESPRIT trial. RESULTS: A total of 901 patients received a loading dose of thienopyridine before PCI (group 1), 123 received thienopyridine pretreatment without a loading dose (group 2), and 1,016 were not treated with thienopyridine before PCI (group 3). The composite incidence of death or myocardial infarction at 30 days was significantly lower in group 1 than in groups 2 and 3 combined (OR, 0.71 [95%CI, 0.52-0.99]; P = 0.0417). A similar trend was seen for the composite of death, myocardial infarction, or urgent target vessel revascularization (unadjusted OR, 0.77 [0.57-1.05]; P = 0.1025). After adjusting for baseline characteristics, these differences were no longer significant. No interactions were identified with eptifibatide assignment for any of the group comparisons. CONCLUSIONS: Pretreatment with a loading dose of thienopyridine lowers the rate of ischemic complications regardless of treatment with a GP IIb/IIIa inhibitor. Conversely, the efficacy of eptifibatide is maintained whether or not a loading dose of a thienopyridine is administered. Optimal outcomes are achieved in patients receiving thienopyridine pretreatment along with platelet GP IIb/IIIa inhibitor therapy.     

Lack of clopidogrel pretreatment effect on the relative efficacy of bivalirudin with provisional glycoprotein IIb/IIIa blockade compared to heparin with routine glycoprotein IIb/IIIa blockade: a REPLACE-2 substudy

OBJECTIVES: The purpose of this study was to assess if clopidogrel pretreatment affects the relative efficacy of bivalirudin versus heparin with glycoprotein (GP) IIb/IIIa blockade for percutaneous coronary interventions (PCI). BACKGROUND: Although thienopyridine pretreatment may improve clinical outcomes with PCI, it is unknown if bivalirudin's efficacy compared with heparin is dependent upon such pretreatment. METHODS: The Randomized Evaluation in Percutaneous coronary intervention Linking Angiomax to reduced Clinical Events (REPLACE-2) trial was a double-blind, triple-dummy, randomized-controlled trial comparing heparin plus routine GP IIb/IIIa blockade (heparin group) with bivalirudin plus provisional GP IIb/IIIa blockade (bivalirudin group) during PCI. The primary end point was a composite of death, myocardial infarction (MI), urgent revascularization at 30 days, and major in-hospital bleeding. The secondary end point was a 30-day composite of death, MI, and urgent revascularization. Clopidogrel pretreatment was encouraged (300 mg loading, 75 mg/day). RESULTS: Of 6,010 patients enrolled, 5,893 received clopidogrel, with 85.8% in the bivalirudin and 84.6% in the heparin group receiving clopidogrel pretreatment. Bivalirudin (provisional GP IIb/IIIa blockade 7.2%) was noninferior to the heparin group for both primary and secondary end points. Clopidogrel pretreatment did not affect the relative efficacy of bivalirudin versus heparin with GP IIb/IIIa blockade, irrespective of pretreatment duration. Pretreatment was associated with significantly lower primary end point with bivalirudin (8.7% pretreatment vs. 12.9% no pretreatment, p = 0.007), and nonsignificantly with heparin (9.7% vs. 11.7%, respectively, p = 0.20). Multivariable models showed a trend toward lower primary and secondary end points with clopidogrel pretreatment. CONCLUSIONS: Clopidogrel pretreatment at the doses and time administered in this trial did not influence the relative efficacy of bivalirudin versus heparin plus GP IIb/IIIa blockade for PCI. However, pretreatment was associated with a trend towards lower clinical events after PCI.     

Effect of additional temporary glycoprotein IIb/IIIa receptor inhibition on troponin release in elective percutaneous coronary interventions after pretreatment with aspirin and clopidogrel (TOPSTAR trial)

OBJECTIVES: The Troponin in Planned PTCA/Stent Implantation With or Without Administration of the Glycoprotein IIb/IIIa Receptor Antagonist Tirofiban (TOPSTAR) trial investigated: 1) the amount of troponin T (TnT) release after nonacute, elective percutaneous coronary intervention (PCI) in patients pretreated with aspirin and clopidogrel; and 2) the effect of additional glycoprotein (GP) IIb/IIIa receptor inhibiton on postinterventional TnT release. BACKGROUND: No data are available yet as to whether additional administration of a GP IIb/IIIa receptor antagonist might be beneficial in patients undergoing elective PCI already pretreated with aspirin and clopidogrel. METHODS: After bolus application of the study medication (tirofiban [T] or placebo [P]), PCI was performed followed by an 18-h continuous infusion of T/P. Primary end point of the study was incidence and amount of TnT release after elective PCI after 24 h. RESULTS: A total of 12 h after PCI troponin release was detected in 63% of the patients receiving P and in 40% of the patients receiving T (p < 0.05), after 24 h in 69% (P) and 48% (T) (p < 0.05) and after 48 h in 74% (P) versus 58% (T) (p < 0.08) of the patients. No differences were observed regarding major bleeding, intracranial bleeding or nonhemorrhagic strokes. After nine months a reduction of combined death/myocardial infarction/target vessel revascularization could be observed in the tirofiban group ([T] 2.3% vs. [P] 13.04%, p < 0.05). CONCLUSIONS: Troponin T release occurs after successful intervention in 74% of the patients undergoing elective PCI after 48 h even after pretreatment with aspirin and clopidogrel. The GP IIb/IIIa receptor antagonist tirofiban is able to decrease the incidence of troponin release significantly in this patient population.