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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. [ABSTRACT FROM AUTHOR]

Background: There is limited information about the association between diabetes, its treatment, and long-term angiographic and clinical outcomes in patients undergoing coronary artery bypass graft surgery (CABG). We evaluated the association of diabetes and its treatment with 1-year angiographic graft failure and 5-year clinical outcomes in patients undergoing CABG., Methods: Using data from 3,014 patients in PREVENT IV, we analyzed angiographic and clinical outcomes in patients with and without diabetes and among those who did and did not receive insulin before CABG. Logistic regression and Cox proportional hazards models were used to adjust for differences in baseline variables., Results: Overall, 1,139 (37.8%) patients had diabetes. Of these, 305 (26.8%) received insulin. One-year rates of vein graft failure were similar in patients with and without diabetes but, among diabetics, tended to be higher in patients who received insulin compared with those who did not. At 5 years, rates of death, myocardial infarction, or revascularization were higher among patients with compared with those without diabetes (adjusted hazard ratio 1.57; 95% CI 1.26-1.96; P < .001) and, among diabetics, higher among those who received insulin (adjusted hazard ratio 1.15; 95% CI 1.02-1.30; P = .02)., Conclusions: Patients with diabetes had similar rates of vein graft failure but worse clinical outcomes than patients without diabetes. Patients who received insulin had significantly worse clinical outcomes than patients who did not receive insulin. Further studies to better understand the mechanism behind these findings and to improve the outcomes of patients with insulin-requiring diabetes undergoing CABG surgery are warranted., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To evaluate angiographic and clinical outcomes associated with open and closed dissection tunnel endoscopic vein harvesting (EVH) devices., Background: A previous PREVENT-IV (PRoject of Ex-vivo Vein graft ENgineering via Transfection IV) analysis reported that EVH for coronary artery bypass graft surgery was associated with worse outcomes than with traditional vein harvesting; however, outcomes by EVH device type were not available., Methods: Using data from the PREVENT-IV trial, we compared 1549 patients from 75 surgical sites who underwent EVH with open (n = 390) or closed (n = 1159) harvest tunnel devices. Outcomes included the incidence of vein graft failure at 12 to 18 months and a composite of death, myocardial infarction, and revascularization through 5 years., Results: Among patients undergoing open and closed tunnel EVH, no difference in the per-patient incidence of vein graft failure (43.8% vs 47.1%; adjusted odds ratio, 0.91; 95% confidence interval, 0.53-1.55; P = 0.724) or per-graft incidence of vein graft failure (25.5% vs 25.9%; adjusted odds ratio, 0.96; 95% confidence interval, 0.59-1.55; P = 0.847) was observed. At 5 years, no difference was observed in the primary composite clinical outcome between patients who underwent open and closed system EVH (21.5% vs 23.9%; adjusted hazard ratio, 0.85; 95% confidence interval, 0.66-1.10; P = 0.221)., Conclusions: No differences in angiographic or clinical outcomes were observed among patients who underwent open versus closed tunnel endoscopic harvesting for coronary bypass surgery. These findings suggest that the risks associated with EVH that were reported in a previous PREVENT-IV analysis are not related to a specific EVH device.

Dual antiplatelet therapy with both aspirin and clopidogrel is increasingly used after coronary artery bypass grafting (CABG); however, little is known about the safety or efficacy. We sought to determine the relationship between postoperative clopidogrel and clinical and angiographic outcomes following CABG. We evaluated 3,014 patients from PREVENT IV who underwent CABG at 107 US sites. Postoperative antiplatelet therapy was left to physician discretion. Risk-adjusted angiographic and clinical outcomes were compared in patients taking and not taking clopidogrel 30 days post-CABG. At 30 days, 633 (21%) patients were taking clopidogrel. Clopidogrel users were more likely to have peripheral vascular (15 vs. 11%) and cerebrovascular disease (17 vs. 11%), prior myocardial infarction (MI) (46 vs. 41%), and off-pump surgery (33 vs. 18%). Clopidogrel use was associated with statistically insignificant higher graft failure (adjusted odds ratio 1.3; 95% confidence interval [CI] [1.0, 1.7]; P = 0.05). At 5-year follow-up, clopidogrel use was associated with similar composite rates of death, MI, or revascularization (27 vs. 24%; adjusted hazard ratio 1.1; 95% CI [0.9, 1.4]; P = 0.38) compared with those not using clopidogrel. There was an interaction between use of cardiopulmonary bypass and clopidogrel with a trend toward lower 5-year clinical events with clopidogrel in patients undergoing off-pump CABG. In this observational analysis, clopidogrel use was not associated with better 5-year outcomes following CABG. There may be better outcomes with clopidogrel among patients having off-pump surgery. Adequately powered randomized clinical trials are needed to determine the role of dual antiplatelet therapy after CABG.

Background: Edifoligide, an E2F transcription factor decoy, does not prevent vein graft failure or adverse clinical outcomes at 1 year in patients undergoing coronary artery bypass grafting (CABG). We compared the 5-year clinical outcomes of patients in PREVENT IV treated with edifoligide and placebo to identify predictors of long-term clinical outcomes., Methods: A total of 3,014 patients undergoing CABG with at least 2 planned vein grafts were enrolled. Kaplan-Meier curves were generated to compare the long-term effects of edifoligide and placebo. A Cox proportional hazards model was constructed to identify factors associated with 5-year post-CABG outcomes. The main outcome measures were death, myocardial infarction (MI), repeat revascularization, and rehospitalization through 5 years., Results: Five-year follow-up was complete in 2,865 patients (95.1%). At 5 years, patients randomized to edifoligide and placebo had similar rates of death (11.7% and 10.7%, respectively), MI (2.3% and 3.2%), revascularization (14.1% and 13.9%), and rehospitalization (61.6% and 62.5%). The composite outcome of death, MI, or revascularization occurred at similar frequency in patients assigned to edifoligide and placebo (26.3% and 25.5%, respectively; hazard ratio 1.03 [95% CI 0.89-1.18], P = .721). Factors associated with death, MI, or revascularization at 5 years included peripheral and/or cerebrovascular disease, time on cardiopulmonary bypass, lung disease, diabetes mellitus, and congestive heart failure., Conclusions: Up to a quarter of patients undergoing CABG will have a major cardiac event or repeat revascularization procedure within 5 years of surgery. Edifoligide does not affect outcomes after CABG; however, common identifiable baseline and procedural risk factors are associated with long-term outcomes after CABG., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Background: Vein-graft harvesting with the use of endoscopy (endoscopic harvesting) is a technique that is widely used to reduce postoperative wound complications after coronary-artery bypass grafting (CABG), but the long-term effects on the rate of vein-graft failure and on clinical outcomes are unknown., Methods: We studied the outcomes in patients who underwent endoscopic harvesting (1753 patients) as compared with those who underwent graft harvesting under direct vision, termed open harvesting (1247 patients), in a secondary analysis of 3000 patients undergoing CABG. The method of graft harvesting was determined by the surgeon. Vein-graft failure was defined as stenosis of at least 75% of the diameter of the graft on angiography 12 to 18 months after surgery (data were available in an angiographic subgroup of 1817 patients and 4290 grafts). Clinical outcomes included death, myocardial infarction, and repeat revascularization. Generalized estimating equations were used to adjust for baseline covariates associated with vein-graft failure and to account for the potential correlation between grafts within a patient. Cox proportional-hazards modeling was used to assess long-term clinical outcomes., Results: The baseline characteristics were similar between patients who underwent endoscopic harvesting and those who underwent open harvesting. Patients who underwent endoscopic harvesting had higher rates of vein-graft failure at 12 to 18 months than patients who underwent open harvesting (46.7% vs. 38.0%, P<0.001). At 3 years, endoscopic harvesting was also associated with higher rates of death, myocardial infarction, or repeat revascularization (20.2% vs. 17.4%; adjusted hazard ratio, 1.22; 95% confidence interval [CI], 1.01 to 1.47; P=0.04), death or myocardial infarction (9.3% vs. 7.6%; adjusted hazard ratio, 1.38; 95% CI, 1.07 to 1.77; P=0.01), and death (7.4% vs. 5.8%; adjusted hazard ratio, 1.52; 95% CI, 1.13 to 2.04; P=0.005)., Conclusions: Endoscopic vein-graft harvesting is independently associated with vein-graft failure and adverse clinical outcomes. Randomized clinical trials are needed to further evaluate the safety and effectiveness of this harvesting technique., (2009 Massachusetts Medical Society)

Objective: Limited information exists on the impact of preoperative renal dysfunction on internal thoracic artery and saphenous vein graft failure and 2-year clinical outcomes in patients undergoing coronary artery bypass surgery., Methods: We studied the impact of preoperative renal dysfunction (creatinine clearance < 60 mL/min) on 1-year internal thoracic artery and saphenous vein graft failure (defined as > or = 75% angiographic stenosis) and 2-year clinical events (death; death or myocardial infarction; and death, myocardial infarction, or revascularization) in 3014 patients undergoing coronary artery bypass surgery enrolled in the Project of Ex-vivo Vein Graft Engineering via Transfection-IV study., Results: Of 2973 patients (98.6%) with preoperative measurement of renal function, 440 (14.8%) had renal dysfunction. Most baseline comorbidities were higher in these patients. Two-year clinical events were higher in patients with preoperative renal dysfunction (adjusted death, myocardial infarction, or revascularization, hazard ratio 1.21, 95% confidence interval 0.97-1.50; adjusted death or myocardial infarction, hazard ratio 1.35, 95% confidence interval 1.05-1.74; adjusted death, hazard ratio 1.47, 95% confidence interval 0.98-2.21). However, saphenous vein graft (odds ratio 1.02, 95% confidence interval 0.79-1.33) and internal thoracic artery (odds ratio 0.76, 95% confidence interval 0.40-1.44) failure were similar in the 2 groups., Conclusion: Although the risk of adverse clinical events is higher in patients with preoperative renal dysfunction, that of internal thoracic artery and saphenous vein graft failure is not. This suggests that factors other than graft failure account for the worse clinical outcomes in this high-risk cohort. Further studies are needed to identify other mechanisms of these worse outcomes so that appropriate measures can be developed to improve long-term outcomes in patients with renal dysfunction undergoing coronary artery bypass surgery.

Objectives: We determined the contribution of multiple variables to predict arrhythmic death and total mortality risk in patients with coronary disease and left ventricular dysfunction. We then constructed an algorithm to predict risk of mortality and sudden death., Background: Many factors in addition to ejection fraction (EF) influence the prognosis of patients with coronary disease. However, there are few tools to use this information to guide clinical decisions., Methods: We evaluated the relationship between 25 variables and total mortality and arrhythmic death in 674 patients enrolled in the MUSTT (Multicenter Unsustained Tachycardia Trial) study that did not receive antiarrhythmic therapy. We then constructed risk-stratification algorithms to weight the prognostic impact of each variable on arrhythmic death and total mortality risk., Results: The variables having the greatest prognostic impact in multivariable analysis were functional class, history of heart failure, nonsustained ventricular tachycardia not related to bypass surgery, EF, age, left ventricular conduction abnormalities, inducible sustained ventricular tachycardia, enrollment as an inpatient, and atrial fibrillation. The model demonstrates that patients whose only risk factor is EF < or =30% have a predicted 2-year arrhythmic death risk <5%., Conclusions: Multiple variables influence arrhythmic death and total mortality risk. Patients with EF < or =30% but no other risk factor have low predicted mortality risk. Patients with EF >30% and other risk factors may have higher mortality and a higher risk of sudden death than some patients with EF < or =30%. Thus, risk of sudden death in patients with coronary disease depends on multiple variables in addition to EF.

Patients with coronary artery disease, depressed left ventricular ejection fraction, and nonsustained ventricular tachycardia (VT) have a high mortality rate due to arrhythmic (arrhythmic death/cardiac arrest) and other cardiac causes. The Multicenter UnSustained Tachycardia Trial (MUSTT) investigated whether electrophysiologic study (EPS) was helpful in choosing drug or defibrillator therapy in patients induced into sustained VT. The events committee attempted to categorize follow-up events in patients in MUSTT and to present a detailed breakdown of events. A derivative of the Hinkle-Thaler classification was used, incorporating lessons from other multicenter studies. The committee was blinded to results of EPS and implantable cardioverter-defibrillator (ICD) or other antiarrhythmic therapy status of patients. The primary end point was cardiac arrest or death from arrhythmia. Secondary end points were death from all causes, cardiac causes, and spontaneous sustained VT. Classifications were death and cardiac arrest. Each was similarly divided as arrhythmic with 14 subcategories, e.g., unwitnessed or related to EPS and nonarrhythmic with 10 subcategories, e.g., ischemia. Terminal VF in progressive heart failure was considered nonarrhythmic. Events were reviewed by 2 members. Disagreements were resolved by the 2 members or, if needed, by the full committee. Of the 2,202 patients in MUSTT, there were 902 deaths. Sustained VT requiring cardioversion occurred in 182 patients. An additional 94 patients had resuscitated cardiac arrests. Events occurred in 1,027 patients, and all were reviewed. The 3 leading events were deaths that were classed as sudden/unwitnessed (23% of 902), due to progressive heart failure (22%), or due to noncardiovascular causes (18%). Arrhythmic deaths or cardiac arrests were highest in inducible patients randomized to no antiarrhythmic therapy; next were inducible patients receiving an ICD; and lowest were in patients who were noninducible. In conclusion, the classification system provided a detailed breakdown of events in consistent categories, showing utility for event analysis and interpretation and development of therapeutic strategies. The classifications assigned by the committee were used in all MUSTT outcomes reports, thus affecting all reported outcomes and overall interpretations of the MUSTT.

Background: Secondary prevention medications are beneficial after acute coronary syndromes, but these benefits are less clear after coronary artery bypass graft surgery. We investigated whether greater use of secondary prevention medications after coronary artery bypass graft surgery is associated with improved clinical outcomes., Methods: Patients undergoing coronary artery bypass graft surgery in the PREVENT IV trial (n = 2970) were surveyed for use of antiplatelet agents, beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and lipid-lowering agents after hospital discharge and at 1 year. Patients were categorized based on their percentage use of indicated medications after hospital discharge. Cox modeling was used to determine the association between medication use categories and rates of death or myocardial infarction through 2 years after adjustment for clinical factors, the number of indicated medications, and treatment propensity., Results: Rates of use of antiplatelet agents and lipid-lowering agents were high at discharge and at 1 year, but use of beta-blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was suboptimal. There was a stepwise association between medication use at discharge and patient outcomes (p for trend = 0.014). Patients taking 50% or less of indicated medications at discharge had a significantly higher 2-year rate of death or myocardial infarction (8.0% versus 4.2%; adjusted hazard ratio, 1.69; 95% confidence interval, 1.12 to 2.55; p = 0.013) than those taking all indicated medications., Conclusions: Greater use of indicated secondary prevention medications after coronary artery bypass graft surgery is associated with a lower 2-year rate of death or myocardial infarction. These data underscore the importance of appropriate secondary prevention measures to improve long-term clinical outcomes after coronary artery bypass graft surgery.

Background: Practice patterns for percutaneous coronary interventions (PCIs) may differ between Canada and the United States. Few data are available comparing PCI outcomes between the two countries in the era of coronary stenting and adjunctive glycoprotein IIb/IIIa inhibition., Methods: In the Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial, 2064 patients were randomly assigned to receive eptifibatide or placebo during nonurgent PCI. The 30-day and one-year rates of death, myocardial infarction (MI) and target vessel revascularization (TVR) were compared between Canadian and American patients enrolled in the ESPRIT trial., Results: There were 1531 American patients and 533 Canadian patients enrolled. Americans were older and heavier, and had a higher incidence of cardiac risk factors than Canadians (P<0.05 for all variables). Canadian patients had a lower incidence of death, MI and TVR at 30 days (6.2% versus 10.4%, P=0.004) and at one year (14.8% versus 21.5%, P=0.0006). After adjusting for known baseline differences, enrollment in Canada remained a significant predictor of reduced ischemic complications at 30 days (OR=0.53, c2=9.0, P=0.003). Similar results were observed at one year. Eptifibatide was superior to placebo in both groups of patients., Conclusions: This analysis is among the first to show Canadian patients to have fewer adverse events than American patients after nonurgent PCI. This effect was independent of known baseline differences between the patients in each country. The relative treatment effect of eptifibatide in Canadian patients paralleled that observed in the main ESPRIT trial and in American patients.

Introduction: Previous studies have demonstrated gender differences in risk of sudden death in patients with ischemic heart disease. The Multicenter UnSustained Tachycardia Trial (MUSTT) evaluated the ability of therapy guided by electrophysiologic (EP) testing to reduce mortality in patients with coronary disease, ejection fraction < or =40%, and spontaneous nonsustained ventricular tachycardia., Methods and Results: We analyzed the influence of gender on results of EP testing and outcome of patients enrolled in MUSTT. Women made up 14% of the overall MUSTT population and were less likely than men to have inducible sustained randomizable ventricular arrhythmias (24% vs 36%, P < 0.001). Baseline characteristics differed between men and women. In randomized patients, women were older, more likely to have had an infarction within 6 months, more likely to have a history of heart failure, and more likely to have recent angina prior to enrollment than men (P < 0.05). In the EP-guided therapy group, there was no difference in implantable cardioverter defibrillator implantation rate in men and women (45% vs 53%, P = 0.38). There also were no significant gender influences on risk of arrhythmic death or cardiac arrest (2-year event rate 9% in women and 12% in men, adjusted hazard ratio 0.88) or overall mortality (2-year event rate 32% in women vs 21% in men, adjusted hazard ratio 1.51)., Conclusion: The outcome and benefit of EP-guided therapy in this trial did not appear to be influenced by gender. However, due to the small numbers of women in the trial, small differences in outcome may not be apparent. Plans for future primary prevention trials should include careful risk stratification of women who less often have inducible sustained ventricular arrhythmias and better left ventricular function despite more frequent heart failure.

Background: Fifty percent of deaths in patients with coronary disease occur suddenly. Although many factors correlate with increased mortality, there is little information regarding the influence of these factors on mode of death. As such, optimum methods to determine patients most likely to benefit from implantable defibrillator therapy are unclear., Methods and Results: We analyzed the relation of ejection fraction and inducible ventricular tachyarrhythmias to mode of death in all 1791 patients enrolled in the Multicenter Unsustained Tachycardia Trial who did not receive antiarrhythmic therapy. Total mortality and arrhythmic deaths/cardiac arrests occurred more frequently in patients with ejection fraction <30% than in those with ejection fraction of 30% to 40%. The percentage of deaths classified as arrhythmic was similar in patients with ejection fraction <30% or > or =30%. The relative contribution of arrhythmic events to total mortality was significantly higher in patients with inducible tachyarrhythmia (58% of deaths in inducible patients versus 46% in noninducible patients, P=0.004). The higher percentage of events that were arrhythmic among patients with inducible tachyarrhythmia appeared more distinct among patients with an ejection fraction > or =30% (61% of events were arrhythmic among inducible patients with ejection fraction > or =30% and only 42% among noninducible patients, P=0.002)., Conclusions: Both low ejection fraction and inducible tachyarrhythmias identify patients with coronary disease at increased mortality risk. Ejection fraction does not discriminate between modes of death, whereas inducible tachyarrhythmia identifies patients for whom death, if it occurs, is significantly more likely to be arrhythmic, especially if ejection fraction is > or =30%.

Introduction: Nonsustained ventricular tachycardia (NSVT) occurs frequently in the postoperative period (< or = 30 days) after coronary artery bypass graft (CABG) surgery, a setting where many factors may play a role in its genesis. The prognosis of NSVT in this setting in patients with left ventricular (LV) dysfunction is unknown. This study was designed to assess its significance., Methods and Results: We compared the outcome of untreated patients enrolled in the Multicenter Unsustained Tachycardia Trial with coronary artery disease (CAD), LV dysfunction, and NSVT identified postoperatively after CABG (n = 228; mean age 67 years, 84% males) versus nonpostoperative settings (n = 1,302; mean age 66 years, 85% males). Sustained monomorphic ventricular tachycardia was induced in 27% and 33% (P = 0.046) of patients with postoperative and nonpostoperative NSVT, respectively. The 2- and 5-year rates of arrhythmic events were 6% and 16%, respectively, in postoperative patients versus 15% and 29% in nonpostoperative patients (unadjusted P = 0.0020, adjusted P = 0.0082). The 2- and 5-year overall mortality rates were 15% and 36%, respectively, for postoperative patients versus 24% and 47% for nonpostoperative patients (unadjusted P = 0.0005, adjusted P = 0.027). Patients whose NSVT was identified early (<10 days) versus late (10-30 days) after CABG had significantly lower 2- (13% vs 23%) and 5-year (30% vs 52%) mortality rates (unadjusted P = 0.024, adjusted P = 0.018)., Conclusion: In this population of patients with CAD and LV dysfunction, the occurrence of postoperative NSVT, especially within 10 days after CABG, portends a far better outcome than when it occurs in nonpostoperative settings. This suggests that in a such setting, NSVT represents a less specific risk factor for future events and should be considered when assigning risk and treatment of similar patients.

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-microg/kg boluses, 10 minutes apart, with a continuous infusion of 2.0 microg/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.

Objectives: The goal of this study was to describe the influence of the clinical setting (in-hospital vs. out-of-hospital) in which nonsustained ventricular tachycardia (NSVT) is discovered on the rate of inducibility of sustained ventricular tachycardia (VT), arrhythmic events and survival in patients with coronary artery disease (CAD) and left ventricular (LV) dysfunction., Background: In-hospital presentation of sustained VT is independently associated with lower long-term overall survival. The impact of the clinical setting in which NSVT is documented is unknown., Methods: In the Multicenter Unsustained Tachycardia Trial (MUSTT), designed to assess the benefit of randomized antiarrhythmic therapy guided by electrophysiologic testing in patients with asymptomatic NSVT, CAD and LV dysfunction, eligible patients were enrolled irrespective of the setting in which the index arrhythmia was discovered. In this retrospective analysis, we compared the rate of VT inducibility and outcome of MUSTT-enrolled patients with in-hospital versus out-of-hospital presentation of NSVT., Results: Monomorphic sustained VT was induced in 35% and 28% of the patients whose index NSVT occurred in-hospital and out-of-hospital, respectively (adjusted p = 0.006). Cardiac arrest or death due to arrhythmia at two- and five-year follow-ups were 14% and 28% for untreated patients with in-hospital-identified NSVT and 11% and 21% for the out-of-hospital group (adjusted p = 0.10). Overall mortality rates at two- and five-year follow-ups were 24% and 48% for inpatients and 18% and 38% for outpatients (adjusted p = 0.018). In patients randomized to antiarrhythmic therapy, there was no significant interaction between patient status (in-hospital vs. out-of-hospital) and treatment impact on the rates of total mortality (p = 0.98) and arrhythmic events (p = 0.08)., Conclusions: In patients with CAD and impaired LV function, asymptomatic NSVT identified in-hospital, compared with that identified out-of-hospital, is associated with a higher rate of induction of sustained VT and overall mortality. Therefore, in similar patients, the clinical setting in which NSVT is discovered should be taken into account when formulating patient risk, treatment and clinical trial design.

Objectives: Using data from the Multicenter UnSustained Tachycardia Trial (MUSTT), we examined the factors used to select antiarrhythmic drug therapy and their impact on outcomes., Background: The MUSTT examined the use of programmed ventricular stimulation (PVS) to guide antiarrhythmic therapy in patients with coronary arteriosclerosis, left ventricular dysfunction and asymptomatic, unsustained ventricular tachycardia (VT). Trial outcomes may reflect factors used to select antiarrhythmic drug therapy., Methods: We compared subgroups of patients with inducible sustained VT randomized to PVS-guided antiarrhythmic therapy (n = 351), in particular those receiving PVS-guided antiarrhythmic drug therapy (n = 142) versus no antiarrhythmic therapy (controls, n = 353)., Results: "Effective" antiarrhythmic drug therapy (i.e., the term "effective" was used to denote therapy that resulted in noninducible VT or hemodynamically stable induced VT) was found for 142 of the 351 patients (43%), most often at the first or second PVS session (125/142, 88%). Mortality among the 142 patients did not differ from that among control patients. Of these 142 patients, the PVS end point was noninducibility in 91 patients and stable VT in 51 patients. Mortality did not differ between these two groups either, but arrhythmia was numerically more frequent in the PVS-induced stable VT group. Mortality was greatest in the few patients receiving propafenone (unadjusted p = 0.07, adjusted p = 0.14 vs. controls), but mortality with all agents did not differ from that of controls, even after adjustment., Conclusions: Even when presenting the results as favorably as possible, we found no benefit with PVS-guided drug therapy in patients with clinical unsustained VT who had inducible sustained VT. These findings are unaltered by using different end points for PVS or considering the response to individual drugs.

Background: An abnormal signal-averaged ECG (SAECG) is a noninvasive marker of the substrate of sustained ventricular tachycardia after myocardial infarction. We assessed its prognostic ability in patients with asymptomatic unsustained ventricular tachycardia, coronary artery disease, and left ventricular dysfunction., Methods and Results: A blinded core laboratory analyzed SAECG tracings from 1925 patients in a multicenter trial. Cox proportional hazards modeling was used to examine individual and joint relations between SAECG variables and arrhythmic death or cardiac arrest (primary end point), cardiac death, and total mortality. We also assessed the prognostic utility of SAECG at different levels of ejection fraction (EF). A filtered QRS duration >114 ms (abnormal SAECG) independently predicted the primary end point and cardiac death, independent of clinical variables, cardioverter-defibrillator implantation, and antiarrhythmic drug therapy. With an abnormal SAECG, the 5-year rates of the primary end point (28% versus 17%, P=0.0001), cardiac death (37% versus 25%, P=0.0001), and total mortality (43% versus 35%, P=0.0001) were significantly higher. The combination of EF <30% and abnormal SAECG identified a particularly high-risk subset that constituted 21% of the total population. Thirty-six percent and 44% of patients with this combination succumbed to arrhythmic and cardiac death, respectively., Conclusions: SAECG is a powerful predictor of poor outcomes in this population. The noninvasive combination of an abnormal SAECG and reduced EF may have utility in selecting high-risk patients for intervention.

Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce sudden cardiac death and all-cause mortality. They also may have direct antiarrhythmic properties. We retrospectively analyzed the data from the Multicenter UnSustained Tachycardia Trial (MUSTT), to determine the effects of ACE inhibitors on inducibility of sustained ventricular tachycardia and on sudden cardiac death and overall mortality in 2,087 patients with prior myocardial infarction, nonsustained ventricular tachycardia, and depressed left ventricular function. Results of electrophysiologic testing were compared by use of ACE inhibitors at baseline, and outcomes were compared between the 564 patients prescribed ACE inhibitors at discharge and the 1,523 patients who did not receive treatment. The inducibility of sustained ventricular tachycardia during electrophysiologic testing did not differ by baseline ACE inhibitor use (unadjusted p = 0.75). Patients discharged from hospital on ACE inhibitors had a lower ejection fraction, more extensive coronary artery disease, and fewer previous revascularizations at baseline. After adjustments for differences in baseline factors and initial hospitalization variables, there were no significant differences in total mortality (p = 0.47) or arrhythmic death or cardiac arrest (p = 0.51) with ACE inhibitor use at discharge over a median 43 months of follow-up.

Background: Cardiologists often use clinical variables to determine the need for electrophysiological studies to stratify patients for risk of sudden death. It is not clear whether this is rational in patients with coronary artery disease, left ventricular dysfunction, and nonsustained ventricular tachycardia., Methods and Results: We analyzed the first 1721 patients enrolled in the Multicenter UnSustained Tachycardia Trial to determine whether clinical variables could predict which patients would have inducible sustained monomorphic ventricular tachycardia. The rate of inducibility of sustained ventricular tachycardia was significantly higher in patients with a history of myocardial infarction and in men compared with women. There was a progressively increased rate of inducibility with increasing numbers of diseased coronary arteries. There was a significantly lower rate of inducibility in patients with prior coronary artery bypass surgery and in patients who also had noncoronary cardiac disease. The rate of inducibility was higher in patients of white race, patients with recent (