MYOCARDIAL INFARCTION

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1 28 JACC Vol. 29, No. 1 MYOCARDIAL INFARCTION Coronary Stent Placement in Patients With Acute Myocardial Infarction: Comarison of Clinical and Angiograhic Outcome After Randomization to Antilatelet or ALBERT SCHÖMIG, MD, FRANZ-JOSEF NEUMANN, MD, HANNA WALTER, MD, HELMUT SCHÜHLEN, MD, MARTIN HADAMITZKY, MD, EVA-MARIA ZITZMANN-ROTH, MD, JOSEF DIRSCHINGER, MD, JÖRG HAUSLEITER, MD, RUDOLF BLASINI, MD, CLAUS SCHMITT, MD, ECKHARD ALT, MD, ADNAN KASTRATI, MD Munich, Germany Objectives. The Intracoronary Stenting and Antithrombotic Regimen (ISAR) trial is a randomized comarison of combined antilatelet with anticoagulant theray after coronary Palmaz- Schatz stent lacement. The objective of this study was to comare early and late clinical and angiograhic outcome in a subgrou of atients with stent lacement for acute myocardial infarction. Background. Stenting has become a treatment otion for acute myocardial infarction, but it is not known which antithrombotic regimen is more adequate after stent imlantation. Methods. One hundred twenty-three atients with successful stenting after acute myocardial infarction were randomized to receive asirin lus ticloidine or intense anticoagulant theray. Six-month reeat angiograhy was erformed in 101 (86.3%) eligible atients. Results. During the first 30 days after stenting, atients with antilatelet theray had a significantly lower clinical event rate (3.3% vs. 21.0%, 0.005) and stent vessel occlusion rate (0% vs. 9.7%, 0.03) and a trend to fewer cardiac events (1.6% vs. 9.7%, 0.12). After 6 months, the survival rate free of recurrent myocardial infarction was higher in atients with antilatelet theray (100% vs. 90.3%, 0.03), and the rate of stent vessel occlusion was lower (1.6% vs. 14.5%, 0.02). Both grous had comarable restenosis rates (26.5% vs. 26.9%, 0.87). Conclusions. This study demonstrates that combined antilatelet theray after stent lacement in atients with acute myocardial infarction is associated with an overall better clinical and angiograhic outcome than anticoagulant theray. (J Am Coll Cardiol 1997;29:28 34) 1997 by the American College of Cardiology Primary angiolasty is an established intervention in acute myocardial infarction (1 3). However, its success is comromised by limitations, such as oor outcome in atients with an unsuccessful rocedure (4 6), a considerable incidence of early reocclusion (7 9) and a high rate of late restenosis (10,11). Intracoronary thrombus, dissections and residual stenosis have been identified as risk factors for unfavorable outcome after ercutaneous transluminal coronary angiolasty (PTCA) (12 14). Coronary stents may offer a solution because they are able to tack u intimal flas (15) and revent vessel closure after comlicated PTCA (16,17); residual stenosis is minimized by a greater immediate gain in lumen area, which is in art resonsible for a lower restenosis rate than after From the 1. Medizinische Klinik, Klinikum rechts der Isar and Deutsches Herzzentrum, Technische Universität München, Munich, Germany. This study was resented in art at the 45th Annual Scientific Session of the American College of Cardiology, Orlando, Florida, March It was suorted in art by grants from Siemens Medical Systems, Erlangen; Scimed-Boston Scientific, Hilden; and Johnson and Johnson Interventional Systems, Norderstedt, Germany. Manuscrit received May 28, 1996; revised manuscrit received Setember 11, 1996, acceted Setember 25, Address for corresondence: Dr. Albert Schömig, 1. Medizinische Klinik, Klinikum rechts der Isar, Ismaningerstrasse 22, Munich, Germany. balloon angiolasty (18,19). Stents may therefore be a suitable device for imroving reerfusion flow in the infarct-related artery and to maintain better long-term atency. However, concerns about the thrombogenicity of the metal surface of stents adding to the thrombotic burden have discouraged their use in acute myocardial infarction. These concerns were enhanced by initial reorts (16,20,21) in which rescue stenting was associated with an increased risk for subsequent thrombotic stent occlusion in vessels with an initial thrombus. For this reason, reorts describing a few successful cases of stenting in acute myocardial infarction have advocated a more aggressive anticoagulant regimen (22,23) or even intracoronary thrombolytic agents after the rocedure (22). In a recently ublished study (24), we showed that stenting in acute myocardial infarction is feasible and safe. Furthermore, these data indicated that a ost-stenting regimen with asirin and ticloidine may be more effective than intense anticoagulation. This finding was further suorted by consecutive studies reorting good results in acute myocardial infarction without conventional anticoagulant theray (25,26,39). Nevertheless, a randomized trial on the effectiveness of different antithrombotic regimens after stent lacement in the comlicated setting of acute myocardial infarction is lacking by the American College of Cardiology /97/$17.00 Published by Elsevier Science Inc. PII S (96)

2 JACC Vol. 29, No. 1 SCHÖMIG ET AL. STENTING IN ACUTE MYOCARDIAL INFARCTION 29 Abbreviations and Acronyms CABG coronary artery byass graft surgery CK creatine kinase ECG electrocardiogram, electrocardiograhic INR international normalized ratio ISAR Intracoronary Stenting and Antithrombotic Regimen trial MLD minimal lumen diameter PTCA ercutaneous transluminal coronary angiolasty PTT artial thrombolastin time TIMI Thrombolysis in Myocardial Infarction The objectives of the resent study were to analyze the grou of atients with stenting in acute myocardial infarction in the Intracoronary Stenting and Antithrombotic Regimen (ISAR) trial, a randomized comarison of combined antilatelet theray (asirin lus ticloidine) with conventional anticoagulant theray (asirin lus henrocoumon with overlaing intravenous hearin) after successful coronary stent lacement (27). Methods Patient selection. The ISAR trial was designed to assess the effectiveness of two antithrombotic regimens after successful coronary Palmaz-Schatz stent lacement. Patients with acute myocardial infarction within 48 h of the intervention were included in the resent analysis. The diagnosis of acute myocardial infarction was based on tyical chest ain lasting 30 min accomanied by ST segment elevation 0.1 mv in two or more adjacent leads on the electrocardiogram (ECG) and an increase in creatine kinase (CK) concentration to twice the uer limit of normal with a concomitant increase in the CK MB isoenzyme. All atients with an acute myocardial infarction admitted directly to our hosital underwent PTCA as the rimary treatment; 11 atients who had received thrombolytic theray as the rimary treatment at other hositals were also included the study because they were referred to us for ersistent or recurrent symtoms within the time frame set by the study. Extensive coronary artery dissection, comlete vessel closure, residual diameter stenosis 30% after PTCA and lesions in venous byass grafts were indications for stenting. Successful stent imlantation (stent deloyed at the desired osition, leaving a residual stenosis 30%) and written informed consent were the inclusion criteria for the trial. Patients were considered ineligible if they had contraindications to the use of asirin, ticloidine or henrocoumon or absolute indications for anticoagulant theray. Furthermore, atients with cardiogenic shock or mechanical ventilation, or both, before PTCA were excluded. Stent lacement rocedure. The rotocol for stent imlantation at our institution has been reviously described in detail (17). Briefly, atients received intravenous hearin (15,000 U) and asirin (500 mg). Standard monorail balloon catheters were used for angiolasty. After the criteria for stenting were met, single-segment 7-mm or articulated 15-mm Palmaz- Schatz stents (Johnson & Johnson) were crimed by hand onto the angiolasty balloon. The balloons used for stent delivery were chosen to be slightly oversized with resect to the target vessel. In most atients, additional noncomliant balloon catheters (High Energy, Boston Scientific, Hilden, Germany) were used for final, high ressure stent dilation (mean maximal balloon ressure 15.9 atm). One or more stents were imlanted, deending on the length of the lesion or the associated dissection, or both. The choice of stent size, number of stents and balloon was at the oerators discretion. Intravascular ultrasound examination was carried out in 10% of atients. The arterial sheath was removed when the artial thrombolastin time (PTT) was 60 s, usually within 3 h after the intervention. Manual comression of the groin was erformed until local hemostasis was achieved, and a ressure bandage was subsequently alied. Antithrombotic regimen. After the ressure bandage was alied, all atients received an intravenous hearin infusion adjusted to maintain a PTT of 80 to 100 s. In atients assigned to antilatelet theray, hearin infusion was stoed 12 h after the stent lacement rocedure. Ticloidine (250 mg twice daily) (Tiklyd, Sanofi-Winthro, Munich, Germany) was started at the end of the rocedure and continued for 4 weeks. In atients assigned to anticoagulant theray, henrocoumon, a coumarin derivative (Marcumar, Hoffmann-La Roche, Grenzach-Wyhlen, Germany) was initiated after stent lacement and given for 4 weeks. In this grou of atients, hearin was continued for an additional 5 to 10 days, until a stable level of oral anticoagulation was achieved (target international normalized ratio [INR] between 3.5 and 4.5). Both PTT and INR were determined twice daily. Indeendent of the assigned theray, all atients were given asirin (100 mg twice daily) throughout the study. The concomitant cardiac medication was left to the discretion of the attending hysician. Follow-u. Per rotocol, all atients remained in the hosital for at least 14 days to ensure 100% surveillance within this early eriod. Enzyme determinations and ECG recordings were obtained twice daily for the first 3 days and daily afterward. Comlete blood counts were erformed three times a week. Dulex ultrasound of the groin was carried out routinely by oerators unaware of the atient s assigned theray. Coronary angiograhy was reeated whenever recurrent myocardial ischemia was susected. After discharge, atients were seen in our outatient clinic 1 month after the rocedure. Reeat angiograhy was scheduled at 6 months. All eligible atients without angiograhic follow-u were contacted at 6 months. Angiograhic assessment. Angiograms were assessed by oerators who had no knowledge of the assigned theray for Thrombolysis in Myocardial Infarction (TIMI) flow grade (28), resence of dissection (29) or thrombus (30). Quantitative analysis was alied to the reinterventional baseline angiogram, the maximally inflated balloon, the final ost-stenting

3 30 SCHÖMIG ET AL. JACC Vol. 29, No. 1 STENTING IN ACUTE MYOCARDIAL INFARCTION and follow-u angiograms. An edge detection algorithm (AWOS, Siemens, Erlangen, Germany) was used for all measurements, using the contrast-filled, nontaered catheter ti as reference. Actual balloon diameter, coronary reference diameter, minimal lumen diameter (MLD) and ercent diameter stenosis were obtained directly from this software. Elastic recoil was defined as the difference between the diameter of the maximally inflated balloon and the final, ost-stenting MLD. Acute gain was calculated as the difference between the final and the baseline MLD and late loss as the difference between final, ost-stenting MLD and MLD at follow-u angiograhy. Loss index was the calculated ratio of late loss to acute gain. Restenosis was defined as a diameter stenosis 50% at reeat angiograhy. Angiograhic outcome at follow-u was assessed in terms of restenosis rate, MLD and late lumen loss. Definition of events. Clinical events were categorized as cardiac and noncardiac events. Cardiac events were defined as death of cardiac origin, myocardial infarction, aortocoronary byass surgery (CABG) or reeat PTCA of the stented vessel. All deaths were considered cardiac unless a noncardiac etiology had been established by autosy. Diagnosis of recurrent infarction was based on tyical chest ain with new ECG changes and an increase in creatine kinase. Cardiac events were monitored throughout the follow-u eriod. Noncardiac events were defined as death other than cardiac, cerebrovascular accident, severe eriheral vascular event or severe hemorrhagic event. A diagnosis of cerebrovascular accident was made when a rolonged neurologic deficit was resent. Severe eriheral vascular events were seudoaneurysms or arteriovenous fistula at the access site requiring oeration, and severe hemorrhagic events were defined as bleeding comlications requiring oeration or blood transfusions, or both (18). Diagnosis of stent vessel occlusion was based on angiograhic TIMI flow grade 0 or 1. Reeat angiograhy was erformed for symtoms or as scheduled by the rotocol. Statistical analysis. Discrete variables were exressed as counts and comared with the Fisher exact test. Continuous variables were exressed as mean value SD and comared by means of unaired, two-tailed t tests if normally distributed; otherwise they were exressed using median and 2nd and 3rd quartiles and statistically analyzed by means of the Mann- Whitney U test. Because no atient was lost to follow-u, event rates were analyzed with the Fisher exact test. The resective relative risk, including the exact 95% confidence interval, was comuted for the grou with antilatelet theray (31,32). Event-free survival curves for all cardiac events and secifically for recurrent myocardial infarction were obtained by the Kalan-Meier method. Statistical significance was assumed at Results During the study eriod, stent lacement was attemted in 146 atients with acute myocardial infarction and was successful in 123 who had been randomized for entry into the ISAR trial (61 to antilatelet theray, 62 to anticoagulant theray). Table 1. Patient Characteristics Antilatelet Age (yr) Women 16 (26.2) 14 (22.6) 0.86 Smoker 34 (55.7) 33 (53.2) 0.92 Hyercholesterolemia 14 (23.0) 17 (27.4) 0.72 Arterial hyertension 31 (50.8) 36 (58.0) 0.53 Diabetes mellitus 8 (13.1) 10 (16.1) 0.83 Multivessel disease 33 (54.1) 39 (62.9) 0.42 Previous CABG 0 (0) 2 (3.2) 0.50 Previous PTCA 4 (6.6) 3 (4.8) 0.98 Data are exressed as mean value SD or number (%) of atients. CABG coronary artery byass graft surgery; PTCA ercutaneous transluminal coronary angiolasty. Sixteen atients were ineligible because of cardiogenic shock or mechanical ventilation before PTCA, four because of unsuccessful stent imlantation, and three did not give consent. In atients randomized, the indication for stent imlantation was abrut closure in 4 atients, dissection in 90 and residual stenosis in 29. Patients in the two theraeutic grous did not differ significantly with resect to baseline clinical (Tables 1 and 2) and angiograhic variables (Table 3). Notably, there was no difference in the frequency of risk factors for atherosclerosis, extent of coronary artery disease, localization and severity of acute myocardial infarction, TIMI flow grade and time delay between the onset of symtoms and intervention. There were stent segments (7 mm)/vessel imlanted in the antilatelet theray grou and stent segments/vessel in the anticoagulant grou ( 0.87). All atients had TIMI grade flow 3 at the end of the stent Table 2. Characteristics of Myocardial Infarction Antilatelet Time from onset of ain to intervention 6 h 22 (36.7) 22 (35.5) h 14 (23.0) 20 (32.3) h 13 (21.7) 13 (21.0) h 12 (20.0) 7 (11.2) 0.30 Q wave MI 49 (80.3) 54 (87.1) 0.44 Non-Q wave MI 12 (19.7) 8 (12.6) 0.44 Prior thrombolytic theray 5 (8.2) 6 (9.7) 0.76 Localization of MI Anterior 28 (45.9) 31 (50.0) 0.78 Lateral 5 (8.2) 6 (9.7) 0.98 Inferior 28 (45.9) 25 (40.3) 0.66 Killi class I 51 (83.6) 51 (82.3) 0.97 II 7 (11.7) 7 (11.3) 0.83 III 3 (5.0) 4 (6.4) 0.98 Peak creatine kinase (U/liter) 1,024 1, , Data are exressed as mean value SD or number (%) of atients. MI myocardial infarction.

4 JACC Vol. 29, No. 1 SCHÖMIG ET AL. STENTING IN ACUTE MYOCARDIAL INFARCTION 31 Table 3. Procedural Data Antilatelet Target vessel LAD 28 (45.9) 27 (43.5) 0.94 LCx 6 (9.8) 9 (14.5) 0.61 RCA 27 (44.3) 25 (40.3) 0.80 Venous byass graft 0 (0) 1 (1.6) 0.99 TIMI 0 or 1 flow 44 (72.1) 46 (74.2) 0.96 Restenotic lesion 6 (9.8) 5 (8.1) 0.98 Dissection before 43 (70.5) 47 (75.8) 0.65 stenting Visible thrombus 48 (78.7) 46 (74.2) 0.71 before stenting GPIIb/IIIa inhibitors after stenting 12 (19.7) 13 (21.0) 0.96 Data are exressed as number (%) of atients. GP glycorotein; LAD left anterior descending coronary artery; LCx left circumflex coronary artery; RCA right coronary artery. lacement rocedure. A total of 25 atients received glycorotein (GP)IIb/IIIa inhibitors (abciximab c7e3, Reoro, Beiersdorf-Lilly, Hamburg, Germany) for residual, angiograhically visible thrombus at the end of the rocedure. Three atients with anticoagulant theray and abciximab had bleeding comlications; no other event occurred during subsequent follow-u in these 25 atients. Early outcome. Clinical events during the first 30 days are summarized in Table 4. The incidence of all clinical events (cardiac and noncardiac) within the first 4 weeks was significantly lower in the antilatelet than in the anticoagulant grou (3.3% vs. 21.0%, 0.005). Cardiac events. The combined cardiac event rate for cardiac death, recurrent myocardial infarction, CABG or reeat PTCA (whichever occurred first) was 1.6% in the antilatelet theray grou and 9.7% in the anticoagulant theray grou ( 0.12), with a similar trend in the rate of myocardial infarction (0% vs. 6.5%, 0.12) and reeat intervention (1.6% vs. 8.1%, 0.21). With anticoagulant theray, all cardiac events were attributed to thrombotic stent vessel occlusion. The single atient in the antilatelet grou with a cardiac event required PTCA for recurrent symtoms resulting from a nonocclusive distal lesion that had not been treated during the initial stenting rocedure; the stent site was widely atent. Stent vessel occlusion. There was a significantly lower rate of stent vessel occlusion in atients with antilatelet theray (0% vs. 9.7%, 0.03). All six atients in the anticoagulant grou with this comlication subsequently had an adverse event: One died as a result of extensive myocardial infarction; three had a nonfatal recurrent myocardial infarction; one had a symtomatic and one an asymtomatic stent vessel occlusion; all five surviving atients required either CABG (one atient) or reeat PTCA (four atients). When these six atients were comared with the grou without stent vessel occlusion, there was no significant difference in target vessel size (baseline reference diameter 2.90 vs mm, 0.34) and residual stenosis after stent lacement (2.6% vs. 1.7%, 0.88). Three atients had a residual dissection after stent lacement (vs. 16.7% in atients without stent vessel occlusion, 0.15). The number of stent segments deloyed was significantly higher in atients with stent vessel occlusion (4.3 vs. 2.7, 0.02). No atient had angiograhic evidence of a residual thrombus at the end of the intervention; intravascular ultrasound was not erformed. Noncardiac events. Antilatelet theray was associated with a significantly lower risk of noncardiac events (1.6% vs. 12.9%, 0.03). This was a result of a lower incidence of hemorrhagic events (0% vs. 12.9%, 0.007) in the antilatelet theray grou. One atient in the antilatelet grou had an ischemic stroke 2 h after the stent lacement rocedure, during theraeutic hearin infusion. Table 4. Clinical Events During First 30 Days After Intervention Antilatelet RR (95% CI) Any clinical event 2 (3.3) 13 (21.0) ( ) Cardiac event 1 (1.6) 6 (9.7) (0 1.34) Death or reeat MI 0 4 (6.5) (0 1.10) Death 0 1 (1.6) 0.99 MI 0 4 (6.5) (0 1.10) Reeat intervention 1 (1.6) 5 (8.1) (0 1.70) CABG 0 1 (1.6) 0.99 PTCA 1 (1.6) 4 (6.5) (0 2.47) Occlusion of stent vessel 0 6 (9.7) (0 0.64) Noncardiac event 1 (1.6) 8 (12.9) (0 0.90) Cerebrovascular accident 1 (1.6) Hemorrhagic events 0 8 (12.9) (0 0.45) Periheral vascular events 0 1 (1.6) 0.99 Data are exressed as number (%) of atients. CI confidence interval; RR relative risk; other abbreviations as in Table 1.

5 32 SCHÖMIG ET AL. JACC Vol. 29, No. 1 STENTING IN ACUTE MYOCARDIAL INFARCTION Table 5. Quantitative Angiograhic Data Figure 1. Event-free survival curves for all cardiac events in both treatment grous. Late outcome. Cardiac events. The event-free survival curve for all cardiac events (cardiac death, myocardial infarction, CABG and PTCA of the target vessel) is dislayed in Figure 1. The benefit of the antilatelet theray observed during the first month after stenting was maintained throughout the follow-u eriod. A total of 11 atients (18.0%) treated with initial antilatelet theray and 15 (24.2%) with initial anticoagulation had a cardiac event during this eriod ( 0.54). The majority of events after the first month were reeat interventions: Eight atients in each grou had reeat PTCA, and two atients with antilatelet theray required CABG. Two further cardiac deaths (both due to rogressive heart failure) occurred in the anticoagulant theray grou after the first month, none with antilatelet theray. At 6 months, the initial difference in the rate of death or recurrent myocardial infarction became significant, with 9.7% in atients with initial anticoagulant theray versus 0% with antilatelet theray ( 0.03). Survival free of recurrent myocardial infarction is illustrated in Figure 2. Not included in this analysis is one atient in the anticoagulant theray grou who died of documented bronchial carcinoma in the fourth month after stent lacement. Angiograhic results. Six months after stent lacement, 101 (86.3%) of the eligible atients had had follow-u angiograhy. These data are illustrated in Table 5. There was no significant difference between the two treatment grous in either the restudy rate (83.1% vs. 90%, 0.44) or the time interval from stenting rocedure (195 days, interquartile range Antilatelet (n 49) (n 52) Before stenting Reference diameter (mm) Minimal lumen diameter (mm) Diameter stenosis (%) Immediately after stenting Reference diameter (mm) Minimal lumen diameter (mm) Diameter stenosis (%) At 6-mo follow-u Reference diameter (mm) Minimal lumen diameter (mm) Diameter stenosis (%) Balloon/vessel ratio Elastic recoil (mm) Acute lumen gain (mm) Late lumen loss (mm) Loss index Restenosis rate (%) Data are exressed as mean value SD or as ercent of target vessels. 180 to 207 vs. 194 days, interquartile range 179 to 203, 0.65). Angiograhy revealed three further stent vessel occlusions with initial anticoagulant and one with initial antilatelet theray. As illustrated in Figure 3, the cumulative rate of stent vessel occlusion was 1.6% in the antilatelet grou and 14.5% in the anticoagulant theray grou ( 0.02). The quantitative angiograhic analysis did not show any significant difference in the baseline and ost-stenting variables, including elastic recoil and acute lumen gain. At followu, the mean minimal lumen diameter was mm in the antilatelet and mm in the anticoagulant theray grou (Fig. 4). There were no significant differences in diameter stenosis, late lumen loss and loss index. Thirteen atients treated with initial antilatelet and 14 with anticoagulant theray demonstrated restenosis at angiograhic followu, resulting in a restenosis rate of 26.5% for the antilatelet grou and 26.9% for the anticoagulant theray grou ( 0.87). Figure 2. Survival curves free of recurrent myocardial infarction in both treatment grous. Figure 3. Cumulative rate of stent vessel reocclusion in both treatment grous.

6 JACC Vol. 29, No. 1 SCHÖMIG ET AL. STENTING IN ACUTE MYOCARDIAL INFARCTION 33 Figure 4. Cumulative distribution curves for minimal lumen diameter before (Pre), immediately after stenting (Post) and at angiograhic follow-u for both treatment grous. Discussion Patients with acute myocardial infarction are at high risk for comlications during coronary interventions (33), in articular atients with dissections or thrombi at the target lesion. Desite the high risk rofile of this subset of atients randomized in the ISAR trial, the resent analysis demonstrates that antilatelet theray may considerably imrove the outcome after stenting in acute myocardial infarction. Reocclusion of stented vessel. Patency of the infarctrelated artery is a strong redictor of early and late outcome of atients with acute myocardial infarction (10,33 36). However, reocclusion after rimary PTCA in acute myocardial infarction has been observed in 10% to 25% of atients (7,8). In earlier reorts (23) of stenting in acute myocardial infarction, the reocclusion rate with initial anticoagulant theray was 10%. The main finding of the resent study is a significant reduction in the incidence of stent vessel occlusion by antilatelet theray: The cumulative reocclusion rate was 1.6% for antilatelet theray comared with 14.5% for anticoagulant theray (Fig. 3). When atients with stent vessel occlusion were comared with those without such an event, the number of stent segments deloyed was significantly higher; other rocedural and angiograhic variables were not significantly different. This finding might suggest that atients with rocedures in longer lesions have a higher risk for subsequent stent vessel occlusion if they receive anticoagulant theray. However, samle sizes in the resent study were too small to allow comrehensive analysis of the risk for stent vessel occlusion. Clinical outcome. Antilatelet theray was associated with a significantly lower rate of noncardiac events (1.6% vs. 12.9%), a trend for fewer cardiac events (1.6% vs. 9.7%) and a higher rate free of myocardial infarction than anticoagulant theray. In a recent reliminary reort from the French Registry of Stenting in Acute Myocardial Infarction (26), significantly higher cardiac mortality and nonfatal myocardial infarction rates were observed in the anticoagulant grou than in the antilatelet grou. Comarison of these data with our results is limited because inclusion criteria and clinical characteristics were not reorted, and a slightly different antithrombotic regimen, including low molecular weight hearin in addition to asirin and ticloidine was used after stenting. Angiograhic restenosis. Angiograhic follow-u did not reveal a significant difference between the two treatment grous with resect to restenosis rate and other angiograhic indexes of restenosis, desite the favorable influence of antilatelet theray on the incidence of thrombotic stent occlusions. Saito et al. (37) recently reorted a 17% restenosis rate in atients with stenting for acute myocardial infarction treated without Coumadin. However, these data were obtained in selected atients with target vessels 2.5 mm in diameter, with an angiograhic follow-u rate of 65%. Violaris et al. (38) recently found that angiograhic evidence of thrombus before PTCA was associated with a higher incidence of vessel occlusion during follow-u. However, when totally occluded vessels were excluded from this analysis, the restenosis rate was similar to that in atients without thrombus. The results of the resent study comaring two different antithrombotic regimens are concordant with observations in revious studies, where numerous harmacologic efforts were ineffective in reducing the restenosis rate (39). Restenosis occurred at 6 months in 27% of atients in our study, whereas in other studies it was observed in almost 50% after rimary PTCA for acute myocardial infarction (10,11,37). These angiograhic data suggest that stenting in acute myocardial infarction may result in a markedly lower long-term restenosis rate than rimary PTCA. Limitations of the study. In this study we analyzed a subset of the ISAR trial atients with stent lacement for acute myocardial infarction. The two grous constituted a relatively small series, and the number of atients with adverse events was low. These factors have to be considered in interreting our data. The target INR of 3.5 to 4.5 with anticoagulant theray in the ISAR trial was higher than that currently used or recommended and relatively high comared with other studies (18,19). Although the rate of bleeding comlications comares well with revious reorts (i.e., Belgian Netherlands Stent study [BENESTENT] [19], 13.5%), a lower target INR might have resulted in a lower rate of bleeding comlications. Some comarisons in the resent study were made with historical data for PTCA in atients with acute myocardial infarction. However, randomized studies comaring rimary PTCA with stent lacement in acute myocardial infarction are necessary for a reliable assessment of the best management strategy. In roviding favorable data with regard to antilatelet theray, this study may hel to determine the most aroriate ost-stenting treatment in future randomized trials. Conclusions. This study demonstrates that the outcome after coronary stent lacement in atients with acute myocardial infarction is imroved by combined antilatelet theray comared with conventional anticoagulant theray. The major benefits achieved were a significant lowering of the rate of

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