the high-risk, post-MI patient. In the words of the trialinvestigators, the decision between these 2 therapies“will depend on cumulative clinical experience, tolera-bility, safety, convenience, and cost.”4

References1. Pfeffer MA, Braunwald E, Moye LA, et al. Effect of captopril on

mortality and morbidity in patients with left ventricular dysfunctionafter myocardial infarction: results of the Survival and VentricularEnlargement trial. N Engl J Med 1992;327:669–77.

2. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators.Effect of ramipril on mortality and morbidity of survivors of acutemyocardial infarction with clinical evidence of heart failure. Lancet1993;342:821–8.

3. Dickstein K, Kjekshus J. Effects of losartan and captopril on mortal-ity and morbidity in high-risk patients after acute myocardial infarc-tion: the OPTIMAAL randomised trial. Lancet 2002;360:752–60.

4. Pfeffer MA, McMurray JV, Velazquez EJ, et al. Valsartan, captopril,or both in myocardial infarction complicated by heart failure, leftventricular dysfunction, or both. N Engl J Med2003;349:1893–906.

SessionLate-Breaking Clinical Trials

Study: DEFINITE (Prophylactic Implantation of a Defi-brillator in Patients with Non-Ischemic DilatedCardiomyopathy)

Presenter: Dr Alan Kadish, Northwestern University ofMedicine, Chicago, Ill

Background: Patients with congestive heart failure(CHF) are at substantial risk for sudden cardiac death.Recent studies have shown that patients with ischemiccardiomyopathy and a left ventricular ejection fraction(EF) �30% have a survival benefit from implantablecardioverter defibrillators (ICD).1 However, it is un-known if patients with nonischemic cardiomyopathybenefit from ICD implantation for primary preventionof sudden cardiac death.

The DEFINITE trial’s primary hypothesis was thatprophylactic ICD implantation would improve survivalin patients with nonischemic cardiomyopathy. Patientswho met the following major inclusion criteria at 48centers were enrolled: nonischemic dilated cardiomy-opathy, symptomatic heart failure, EF �35%, and spon-taneous premature ventricular complexes or nonsus-tained ventricular tachycardia. The major exclusioncriteria were prior cardiac arrest, ventricular tachycar-dia of �15 beats, any proximal coronary lesion �50%or distal lesion �75%, NYHA class IV, amiodaronetreatment or electrophysiological study within 3months. The primary end point was total mortality,but an important secondary end point was arrhythmicmortality. Because of interim analyses, a P value of

.0367 was considered statistically significant for theprimary end point.

Results: A total of 458 patients were randomized toICD implantation or optimal medical therapy. Patientswere followed-up for a mean of 26 months and themean EF was 21%. The majority of patients weretreated with ACE inhibitors (86%) and �-blockers(85%). There were 33 deaths in the standard therapygroup and 23 in the ICD group. The hazard ratio was0.66 (95% CI 0.39–1.12, P � .06). Mortality at 2 yearswas 13.8% in the standard-therapy group and 8.1% inthe ICD group. There were 11 arrhythmic deaths fromcardiac arrest in the standard-therapy group and 3 inthe ICD group, giving a hazard ratio of 0.26 (95% CI0.072–0.93, P � .01).

Interpretation: The study’s primary end point was notstatistically significant for ICD therapy, although thesecondary end point of arrhythmic death favored ICDtherapy. The study’s promising results will need fur-ther validation, and studies to be completed in thenear future will answer how patients with nonisch-emic dilated cardiomopathy should be treated to pre-vent sudden cardiac death.

Reference1. Moss AJ, Zareba W, Hall WJ, et al. Improved survival with an im-

planted defibrillator in patients with coronary disease at high riskfor ventricular arrhythmia. Multicenter Automatic Defibrillator Im-plantation Trial Investigators. N Engl J Med 2002;346:877–83.

SessionLate-Breaking Clinical Trials

Study: BRAVE: Bavarian Reperfusion Alternatives Eval-uation–Reteplase plus abciximab or abciximab aloneprior to PCI in AMI patients

Presenter: Dr Adnan Kastrati, Deutsches Hezzentrum,Munich, Germany

Background: Percutaneous coronary intervention(PCI) is superior to fibrinolysis for patients with acutemyocardial infarction (AMI) when done rapidly (door-to-balloon times �90–120 min) and in experiencedcenters.1 Because most medical centers in the worlddo not have onsite interventional catheterization capa-bilities, considerable delay can be routinely encoun-tered before PCI. Increasing delays to reperfusion havebeen associated with increased mortality and morbidi-ty.2 Also, patients who present with an open arterybefore primary angioplasty have improved outcomes.3

Therefore, the concept of “facilitation” before the PCIwith a fibrinolytic or glycoprotein IIb/IIIa inhibitor as away of increasing the likelihood of earlier reperfusion

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appears very promising. The most effective medicalreperfusion therapy before primary PCI is not yet welldelineated.

The BRAVE investigators randomized patients pre-senting with ST-segment elevation AMI within 12hours of symptom onset and chest pain lasting �20minutes to either (1) R�A: half dose reteplase (2 bo-luses of 5 U 30 minutes apart) in combination withabciximab bolus (0.25 mg/kg) followed by a 12-hourinfusion (0.125 mg/kg/min); or (2) A: abciximab bolusand infusion only. The primary end point was infarctsize (as a percentage of the left ventricle) by scinti-graphic study performed 5 to 10 days after randomiza-tion. The study was designed to have 80% power todetect a 30% reduction in infarct size in patientstreated with the combination approach. Secondary endpoints included death, recurrent MI, hemorrhagicstroke, and major bleeding.

Results: A total of 253 patients were randomized andall patients completed angiography. The baseline char-acteristics were similar between the 2 groups (averageage �62 y; 98% Killip I–II; time from symptom onsetto randomization �3 h). Seventy-four percent of thepatients were enrolled from community centers with-out catheterization facilities.

There was no difference in the primary end point ofinfarct size (R�A 13.0% vs A 11.5%, P � .81). Scinti-graphic scanning was completed in �90% of patientsan average of 6 days after the MI. TIMI-3 flow beforePCI was significantly higher in the combination group(R�A 40% vs A 18%, P � .001). There was no signifi-cant difference in death, MI, or stroke. Major bleedingwas more common in the combination group (R�A5.6% vs A 1.6%, P � .16). There was no subgroup inwhich the combination arm was found to be superiorto abciximab alone. Subgroups analyzed included pa-tients randomized within 2 hours of symptom onset,patients with more than a 90-minute delay betweenrandomization and intervention, and patients who re-quired hospital transfer.

Interpretation: This study failed to demonstrate thatfacilitated PCI with a combination strategy of fibrinoly-sis and glycoprotein IIb/IIIa is superior to glycoproteinIIb/IIIa alone for reducing infarct size. However, thestandard deviation of scintigraphy was large and thestudy probably did not have sufficient power to ex-clude a potential benefit of combination therapy. Thesignificantly higher TIMI-3 flow rates seen in the com-bination group are consistent with a potential benefitof combination therapy, but at a price of increasedmajor bleeding. Several large, randomized, controlledtrials of facilitated PCI are currently ongoing and

should provide definitive answers to this importantquestion.

References1. Smith SC Jr, Dove JT, Jacobs AK, et al. ACC/AHA guidelines for

percutaneous coronary interventions (revision of the 1993 PTCAguidelines)-executive summary: a report of the American College ofCardiology/American Heart Association Task Force on PracticeGuidelines (Committee to Revise the 1993 Guidelines for Percutane-ous Transluminal Coronary Angioplasty). J Am Coll Cardiol 2001;37:2215–38.

2. Cannon CP, Gibson CM, Lambrew CT, et al. Relationship of symp-tom-onset-to balloon time and door-to-needle time with mortality inpatients undergoing angioplasty for acute myocardial infarction.JAMA 2000;283:2941–47.

3. Stone GW, Cox D, Garcia E, et al. Normal flow (TIMI 3) beforemechanical reperfusion therapy is an independent determinant ofsurvival in acute myocardial infarction: analysis from the PrimaryAngioplasty in Myocardial Infarction trials. Circulation2001;104:636–41.

SessionLate-Breaking Trials

Study: The Public Access Defibrillation (PAD) Trial

Presenter: Dr Joseph P. Ornato, Department of Emer-gency Medicine, Virginia Commonwealth University,Richmond, Va

Background: The use of automated external defibrilla-tors (AED) by trained emergency medical service(EMS) personnel has been shown to improve out-comes of patients sustaining an out-of-hospital cardiacarrest (OOH-CA). Whether AEDs can have the samebenefit when operated by volunteers in a communitysetting has not been studied prospectively.

The PAD trial was a prospective randomized con-trolled clinical trial comparing 2 lay volunteer-basedOOH-CA response systems. Nonmedical volunteersfrom increased-risk community units were trained torespond to OOH-CA using CPR only or CPR � AED.Study locations had an estimated 50% risk of experi-encing 1 OOH-CA annually and consisted of shoppingand recreation areas, residential areas, entertainmentcomplexes, community centers, office complexes, ho-tels, factories, and transit centers. Community unitswere excluded if their EMS time-to-defibrillation was�15 minutes in �90% of calls or �3 minutes in �10%of calls, or if they had an existing or previous public-access defibrillation (PAD) program. The primary endpoint was survival to hospital discharge, and there wasblinded adjudication of cardiac arrest cases.

Results: A total of 993 community units from 24 re-gional sites across the USA and Canada were random-ized to CPR only or CPR � AED. Overall, 19,762 vol-

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