Early Administration of Reteplase Plus Abciximabvs. Abciximab Alone in Patients With AcuteMyocardial Infarction Referred for PercutaneousCoronary Intervention: A Randomized ControlledTrial

Kastrati A, Mehilli J, Schlotterbeck K, et al, for the BavarianReperfusion Alternatives Evaluation (BRAVE) Study Investigators.JAMA 2004;291:947–54.

Study Question: Does early administration of reteplase plusabciximab produce better results compared with abciximabalone in patients with acute myocardial infarction (MI)referred for percutaneous coronary intervention (PCI)?Methods: In an open-labeled, randomized controlled studyconducted from May 3, 2001 through June 2, 2003, 253patients admitted to 13 community hospitals without cath-eterization facilities (n�186) and to five hospitals withcatheterization facilities (n�67), with the diagnosis of anST-segment elevation acute MI within 12 hours from onsetof symptoms were randomized to receive intravenouslyeither the combination of a half-dose reteplase (two 5-Uboluses, 30 minutes apart) with a standard dose of abcix-imab (0.25 mg/kg bolus, 0.125 �g/kg per minute infusion[maximum 10 �g/min for 12 hours]) (n�125) or the stan-dard dose of abciximab alone (n�128). All patients werethen transferred for PCI. The main outcome of interest wasthe final infarct size determined using a single-photon emis-sion computed tomography study with technetium Tc 99msestamibi performed between 5 and 10 days after random-ization in 228 patients (90.1% of entire sample).Results: The median (interquartile range) of the final infarctsize of the left ventricle was similar in the reteplase plusabciximab group and in the abciximab alone group (13.0%[3.0–28.0%] vs. 11.5% [3.0–26.3%], p�0.81). The meandifference in final infarct size of left ventricle between thereteplase plus abciximab group and the abciximab groupwas 1.3% (95% confidence interval [CI], �3.1–5.7%). Thecomposite secondary end point of death, recurrent MI orstroke within 6 months of randomization occurred in 8patients (6.4%) in the reteplase plus abciximab group and 6patients (4.7%) in the abciximab group (relative risk, 1.4;95% CI, 0.5–3.9; log-rank p�0.56). Major bleeding com-plications were observed in 7 patients (5.6%) in the rete-plase plus abciximab group and 2 patients (1.6%) in theabciximab group (p�0.16).Conclusions: Early administration of reteplase plus abcix-imab does not lead to a reduction of infarct size compared withabciximab alone in patients with acute MI referred for PCI.Perspective: The current study findings should be inter-preted with caution in light of the small number of patientsevaluated. Data from the ongoing Faciliated Intervention

With Enhanced Reperfusion Speed to Stop Events (FI-NESSE) trial, in which 3000 patients with MI will berandomized to either abciximab, abciximab plus reteplaseor no pretreatment before PCI will shed more light on thepotential for facilitated PCI to reduce risk. RM

Abciximab-Supported Infarct Artery StentImplantation for Acute Myocardial Infarction andLong-Term Survival: A Prospective, Multicenter,Randomized Trial Comparing Infarct Artery StentingPlus Abciximab With Stenting AloneAntoniucci D, Migliorini A, Parodi G, et al. Circulation 2004;109:1704 – 6.

Study Question: The impact on survival of routine use ofabciximab as adjunctive treatment to routine infarct arterystenting for acute myocardial infarction is not defined. Theinvestigators sought to determine the effect of abciximab on1-year survival and other major adverse cardiac events ofpatients with acute myocardial infarction undergoing rou-tine infarct artery stenting.Methods: The Abciximab and Carbostent Evaluation (ACE)trial was an unblinded, randomized, controlled trial thatcompared abciximab with placebo in patients undergoingroutine infarct artery stent implantation for acute myocar-dial infarction.Results: At 1 year, the survival rate was 95�2% in theabciximab group and 88�2% in the stent-alone group(p�0.017). The reinfarction rate was 1% in the abciximabgroup and 6.0% in the stent-alone group, whereas therewere no differences between groups in target vessel revas-cularization rate (16.5% in the abciximab group, 17.5% inthe stent-alone group).Conclusions: The authors concluded that abciximab as ad-junctive treatment to routine infarct artery stenting foracute myocardial infarction resulted in improved 1-yearsurvival and lower reinfarction rates.Perspective: Abciximab has consistently shown clinical ben-efits in acute myocardial infarction patients undergoingpercutaneous coronary intervention. This trial suggests thatabciximab may prevent target vessel failure in the earlyphase by virtue of its antiplatelet effect and provide a bettermyocardial reperfusion by virtue of its antithrombotic andanti-inflammatory effects. The latter effects have the poten-tial for reduction of microvessel disruption caused by em-bolization and reperfusion injury. The improved myocardialsalvage in the early phase likely translates into improved sur-vival in the long-term follow-up as seen in this trial. DM

Preprocedural TIMI Flow and Mortality in PatientsWith Acute Myocardial Infarction Treated byPrimary AngioplastyDe Luca G, Ernst N, Zijlstra F, et al. J Am Coll Cardiol 2004;43:1363–7.

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Interventional CardiologyAbstracts

Study Question: Although there is an excellent outcomeconferred by primary angioplasty in patients with STEMI,the prognostic role of early recanalization in these patientshas yet to be investigated. The aim of the study was toevaluate the impact of preprocedural Thrombolysis In Myo-cardial Infarction (TIMI) flow on 1-year mortality in pa-tients with ST-segment elevation myocardial infarction(STEMI) treated by primary angioplasty.Methods: The study population was composed of 1791patients with acute myocardial infarction treated by pri-mary angioplasty at one institution from 1994 to 2001. Allangiographic, clinical and follow-up data were prospec-tively collected. According to the TIMI risk score, patientswere stratified in low- and high-risk groups.Results: Preprocedural TIMI flow was related to postproce-dural TIMI flow grade 3 (p�0.002), myocardial blushgrade 2–3 (p�0.001), enzymatic infarct size (p�0.001),predischarge ejection fraction (p�0.001) and 1-year mor-tality (p�0.05). Multivariate analysis showed that prepro-cedural TIMI flow grade 3 was an independent predictor of1-year survival in high-risk patients (p�0.05).Conclusions: This study shows that preprocedural TIMI flowgrade 3 is an independent predictor of 1-year survival inhigh-risk patients with acute myocardial infarction treatedby primary angioplasty.Perspective: The primary finding of the present study is thatpreprocedural TIMI flow grade 3 is an independent predic-tor of 1-year survival in high-risk patients with STEMI under-going mechanical reperfusion. The results suggest that allefforts should be made to obtain optimal restoration of ante-grade flow as early as possible in patients with STEMI. DM

Atorvastatin Does Not Affect the AntiplateletPotency of Clopidogrel When it Is AdministeredConcomitantly for 5 Weeks in Patients With AcuteCoronary SyndromesMitsios JV, Papathanasiou AI, Rodis FI, Elisaf M, Goudevenos JA,Tselepis AD. Circulation 2004;109:1335– 8.

Study Question: Prior ex vivo studies have suggested that theantiplatelet effect of clopidogrel may be attenuated by short-term coadministration of lipophilic statins. The authorsinvestigated whether the coadministration of atorvastatinfor 5 weeks in patients with acute coronary syndromes(ACSs) could affect the antiplatelet potency of clopidogrel.Methods: The study was an open-labeled prospective trial.45 hypercholesterolemic patients with the first episode ofan ACS were included in the study. Patients were random-ized to receive daily either 10 mg of atorvastatin (n�21) or40 mg of pravastatin (n�24). 30 patients who underwentpercutaneous coronary intervention (PCI) received a load-ing dose of 375 mg of clopidogrel, followed by 75 mg/d forat least 3 months. In the remaining 15 patients who refusedto undergo PCI, clopidogrel therapy was not administered.8 normolipidemic patients with the first episode of an ACS

were also included and received only clopidogrel. Theserum levels of soluble CD40L and the adenosine 5�-diphosphate– or thrombin receptor activating peptide-14–induced platelet aggregation, as well as P-selectin andCD40L surface expression, were studied at baseline (within30 minutes after admission) and 5 weeks later.Results: Neither atorvastatin nor pravastatin significantlyinfluenced the clopidogrel- induced inhibition of platelet acti-vation, nor did clopidogrel influence the therapeutic efficacy ofatorvastatin. Coadministration of clopidogrel with either ator-vastatin or pravastatin inhibited ADP-induced platelet activa-tion to the same extent as that observed for clopidogrel alone.Conclusions: The authors concluded that atorvastatin doesnot affect the antiplatelet potency of clopidogrel when co-administered for 5 weeks in ACS patients.Perspective: The current study demonstrated that the ther-apeutic efficacy of clopidogrel in patients with ACS is notsignificantly influenced by the concomitant administrationof atorvastatin for 5 weeks. Moreover, clopidogrel did notaffect the therapeutic efficacy of atorvastatin. The results areconsistent with data from observational clinical studiessuggesting that the proposed CYP3A4 clopidogrel-statininteraction is likely an ex vivo phenomenon and not likely tobe clinically relevant. DM

Limited Early Antiplatelet Effect of 300 mgClopidogrel in Patients With Aspirin TherapyUndergoing Percutaneous Coronary InterventionsLepantalo A, Virtanen KS, Heikkila J, Wartiovaara U, Lassila R.Eur Heart J 2004;25:476 – 83.

Study Question: The study aim was to evaluate the efficacyand variability of the platelet inhibition exerted by 300 mgclopidogrel for the purpose of acute percutaneous coronaryinterventions (PCIs) using platelet function tests.Methods: The study was a prospective cohort study. Inpatients undergoing elective PCI, clopidogrel was added toongoing acetylsalicylic acid (aspirin) (100 mg/day) at 2.5hours prior to procedure. Blood samples were collectedbefore administration of clopidogrel and immediately be-fore the intervention from 50 patients. Platelet functionswere assessed with traditional aggregation and PFA-100.Results: At baseline, 14 (28%) patients were poor respond-ers to aspirin according to PFA, and 9 patients (18%)continued to show arachidonic acid-induced aggregation.After clopidogrel, ADP-triggered aggregation was onlymodestly inhibited in 40% of the patients. 8% of the studypopulation had no measurable antiplatelet effect. The pa-tients with modest response to clopidogrel had higher levelsof c-peptide (1.5 nmol/L) than the ones responding well(0.9 nmol/L, p�0.05).Conclusions: The authors concluded that neither ongoingaspirin treatment nor added clopidogrel reached an ex-pected extent of platelet inhibition in all patients. Aspirin-treated patients undergoing PCI have highly variable levels

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