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Nonrandomized comparison between stent deployment and percutaneous transluminal coronary angioplasty in acute myocardial infarction
Nonrandomized comparison between stent deployment and percutaneous transluminal coronary angioplasty in acute myocardial infarction Stanley Katz, MD, Stephen J. Green, MD, Barry M. Kaplan, MD, Lisa Chepurko, RN, MBA, Bruce G. Goldner, MD, and Lawrence Ong, MD Manhasset, NY
Background Compared with angioplasty, elective stent implantation has improved short-term and long-term outcome with a decrease in abrupt closure and a reduced 6-month restenosis rate. Although primary angioplasty during acute myocardial infarction has improved outcome, recurrent ischemic events and restenosis are still a problem.
Methods Outcomes for 166 consecutively treated patients who underwent stent insertion procedures within 24 hours after the onset of acute myocardial infarction were compared with those for a similar group of patients (n = 212) who underwent consecutive balloon angioplasty procedures at one tertiary care institution. The objective of this study was to examine in-hospital and late clinical outcomes for the 2 groups.
Results The procedural success rate for stenting in acute myocardial infarction was 100%; that for angioplasty was 98%. Mortality rates during hospitalization were similar for the stent group and the angioplasty group (4.0% vs 2.0%). The rate of inhospital acute reocclusion necessitating urgent percutaneous reintervention was significantly lower for the stent group (0% vs 3%, P = .02). Six months after the procedure, the stent group had a significantly lower need for revascularization of the infarctrelated artery (8% vs 20%, P = .001) and a significantly lower incidence of combined serious clinical events (death, acute occlusion, emergency bypass, target vessel revascularization, and nonfatal myocardial infarction; 12% vs 30%, P = .00003). Conclusion Compared with balloon angioplasty, stent deployment in the setting of acute myocardial infarction was associated with significantly lower frequency of in-hospital acute occlusion and significantly less need for target-vessel revascularization 6 months after myocardial infarction. (Am Heart J 2000;139:44-51.) Primary angioplasty is well documented to be an effective method for obtaining complete reperfusion (Thrombolysis in Myocardial Infarction study [TIMI-3] flow) of the infarction-related artery during an acute myocardial infarction.1,2 Despite the advantages of primary angioplasty over thrombolytic therapy, primary angioplasty is still associated with 10% to 15% risk for recurrent ischemia and reocclusion of the infarctionrelated vessel.3-7 At 6-month follow-up evaluations, rates of restenosis and reocclusion of the infarction-related artery are reported to be as high as 40%.8,9 These adverse outcomes reduce the initial advantage of primary angioplasty over thrombolytic therapy in the management of acute myocardial infarction. This effect was demonstrated in the findings of the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes study (GUSTO II).10 In that study patients who underwent angioplasty had better initial outcomes than From the Division of Cardiology, Department of Internal Medicine, North Shore University Hospital, New York University School of Medicine. Submitted June 12, 1998; accepted October 29, 1998. Reprint requests: Stanley Katz, MD, Division of Cardiology, North Shore University Hospital, 300 Community Dr, Manhasset, NY 11030. Copyright © 1999 by Mosby, Inc. 0002-8703/2000/$12.00 + 0 4/1/95494
those who underwent thrombolytic therapy. Six months after myocardial infarction, however, there was no difference in composite outcomes. Coronary stenting technique has improved, indications have expanded, and there are fewer periprocedural adverse events, such as subacute stent thrombosis.11-13 Elective coronary stenting has been reported to reduce the 6-month rate of restenosis significantly.14-16 Herrmann et al,17 however, showed that stent use in the presence of angiographically visible thrombus was a predictor of subacute stent thrombosis. Therefore it was thought that stent use was contraindicated in the setting of acute myocardial infarction in which a large thrombus burden may predispose a patient to subacute stent thrombosis. In addition to the presence of a large thrombus burden, the presence of dissection or vasospasm, reduced ejection fraction, the frequent occurrence of hypotension, and reduced coronary flow could increase risk for stent thrombosis. Roubin et al,18 in their initial experience with coil stenting after failed angioplasty (in which thrombus and dissection, as in infarction-related arteries, were prevalent) found a significant 7.6% rate of subacute stent thrombosis. Reports of newer techniques have shown primary angioplasty with stent implantation for acute myocardial infarction to be safe with low risk
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for acute thrombotic occlusion, even without the use of warfarin or concomitant intracoronary thrombolytic agents.19,20 These promising observations suggest that stent deployment during early reperfusion of an infarctrelated artery may confer added benefits over use of a balloon alone. In this study, we performed a nonrantdomized comparison of clinical outcomes to compare use of stent deployment during reperfusion of an infarctrelated artery with use of balloon angioplasty alone.
Methods Study Patients We analyzed clinical outcomes among 378 consecutively treated patients with acute myocardial infarction who came to medical attention within 24 hours after symptom onset and underwent interventions to manage the infarct. All patients treated for myocardial infarction during this time period were brought to the catheterization laboratory for possible intervention after written informed consent was obtained. The diagnosis of acute myocardial infarction was based on the typical criteria of chest pain lasting more than 30 minutes accompanied by ST-segment elevation >0.1 mV in 2 or more adjacent ECG leads. Of these patients, 166 received 1 or more intracoronary stents, and 212 underwent balloon angioplasty alone. Stents were implanted at the discretion of the interventional cardiologist. In general the decision was based on perceived ability to deliver the stent to the culprit lesion. In addition to primary infarct interventions, included in this analysis were rescue procedures on patients who had acute myocardial infarction after leaving the catheterization laboratory after elective coronary angioplasty (out-of-laboratory reocclusions). Also included were procedures on patients who had undergone unsuccessful thrombolytic therapy, generally with tissue plasminogen activator, within the previous 24 hours. Stents placed for bail-out purposes were excluded from this analysis.
Data collection In-hospital data were prospectively collected to comply with New York State mandated reporting of all coronary interventions and were available for review. The major clinical events studied during the hospitalization were acute reocclusion, death, and emergency coronary artery bypass grafting (CABG). In-hospital acute reocclusion was defined as clinically driven urgent percutaneous reintervention in the treated artery. Emergency CABG was defined as a bypass operation during hospitalization performed because of a complication from the percutaneous intervention. Six months after the procedure, information on the late clinical outcomes (death, repeat target-vessel revascularization or nonfatal myocardial infarction) were obtained through telephone contact with the patient or an immediate family member by one of the authors. Myocardial infarction was defined as an increase in serum creatine kinase level to more than twice the normal value with new pathologic Q waves. Repeat target-vessel revascularization was defined as a percutaneous coronary intervention or coronary artery bypass operation on the infarct-related vessel for relief of ischemia during the 6 months after discharge from the hospital. Death was defined as death of any cause. Cardiogenic shock in this analysis was
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defined as left ventricular filling pressure greater than 20 mm Hg and systolic blood pressure less than 90 mm Hg.
Angioplasty and stent procedure Ionic contrast material, usually a low osmolar agent (ioxaglate), was used in all instances. For stent implantation, predilation was performed in all cases with the same size balloon as the stent. The Gianturco-Roubin stent was used in 10% (17 of 166) of procedures, usually to preserve a large side branch or because of the length of the lesion. Palmaz-Schatz stents were used in 87% of procedures (145 of 166). A combination of both stents was used in 2% of the procedures (4 of 166). There were 1.3 stents used per patient. Intravascular ultrasound was not used in any procedure. All Palmaz-Schatz stents were postdilated with highpressure balloons to 14 to 18 atm. Left ventriculography was performed during the procedure, before the intervention in most cases.
Anticoagulation therapy Before the procedure, all the patients received aspirin, 975 mg, to chew. Heparin was given as a 10,000-U bolus and readministered as needed to achieve an activated clotting time of more than 300 seconds. When stents were deployed, 250 to 500 mg ticlopidine was given in most instances immediately before the procedure. Intracoronary thrombolytic agents were not given to any patient. Thirteen patients received abciximab as an adjunct to the coronary intervention (4 in the angioplasty group, 9 in the stent group, P = .09). The first 134 patients in this series received a heparin infusion that was initiated after sheath removal and lasted approximately 24 hours. For most of the other patients, heparin infusion was not initiated after the procedure because of a change in local practice. After the procedure, all patients continued aspirin indefinitely. The first 71 stent patients in the series took ticlopidine and warfarin for at least 2 weeks after the procedure. After this, stent patients took only ticlopidine for at least 2 weeks, again because of a change in local practice.
Statistical methods Time from procedure until an event (CABG or repeat intervention after discharge, death after discharge, nonfatal myocardial infarction after discharge, acute occlusion in the hospital, death in the hospital, or emergency CABG in the hospital) was analyzed with the product-limit method and the times were compared by means of the log-rank test. Baseline clinical and angiographic factors were compared between the 2 treatment groups to screen for possible confounding variables. Fisher exact and χ2 tests were used for categorical variables (sex, presence of hypertension, diabetes, smoking, or previous myocardial infarction, infarct-related artery, previous CABG, failed thrombolytic therapy, out-of-laboratory occlusion, presence of cardiogenic shock, whether treatment was within 6 hours of acute myocardial infarction, vessel configuration, and occurrence of major clinical events). The Mann-Whitney test was used for continuous variables (age, left ventricular ejection fraction, final balloon size). Factors significantly related to treatment group in the univariate analysis (P < .05) were used in a
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Table I. Clinical characteristics of 378 patients with acute myocardial infarction Characteristic Age (y) No. of men Hypertension Diabetes Smoking Previous myocardial infarction Previous bypass Unsuccessful thrombolytic therapy Abciximab therapy Out-of-laboratory reocclusion* Cardiogenic shock Time to treatment (h) <6 6–23 Length of stay (d)
Stent group (n = 166)
Angioplasty group (n = 212)
P Value
60 ± 13 120 (72) 107 (64) 23 (14) 54 (33) 30 (18) 9 (5) 32 (19) 9 (5) 4 (2) 6 (4)
63 ± 12 151 (71) 115 (54) 46 (22) 61 (29) 45 (21) 15 (7) 17 (8) 4 (2) 3 (1) 8 (4)
.02 .82 .045 .05 .43 .45 .51 .001 .09 .7 .94
130 (78) 36 (22) 5±4
170 (80) 42 (20) 7±4
.66 .003
Except for age, length of stay, and P value, all values are number with percentage in parentheses. *Patients who underwent elective procedure, left the cardiac catheterization laboratory and then within the same admission, had acute myocardial infarction with closure of the target vessel.
Table II. Angiographic characteristics of patients according to treatment group Characteristic Infarct artery (n and %) Left anterior descending Left circumflex Right Left main Vein graft LV ejection fraction (mean ± SD) Final balloon size (mm; mean ± SD) Morphologic features of lesion (n and %) ACC/AHA class B ACC/AHA class C
Stent group (n = 166)
Angioplasty group (n = 212)
P Value .0001
87 (52) 11 (7) 67 (40) 1 (1) 0 (0) 47 ± 20 3.5 ± 0.5
101 (48) 45 (21) 61 (29) 2 (1) 3 (1) 42 ± 23 3.1 ± 0.5
107 (64) 59 (36)
165 (78) 47 (22)
proportional hazards (Cox) regression analysis to examine the joint (multivariate) effects of those factors.
Results Preprocedure characteristics Between March 4, 1994, and October 31, 1996, 378 patients underwent percutaneous intervention during acute myocardial infarction. When outcomes among patients in the 2 groups were compared with respect to baseline clinical variables, differences were found (Table I). There was more hypertension in the stent group (64% vs 54%, P = .045), were more patients with diabetes in the angioplasty group (22% vs 14%, P = .05), and were more older patients in the angioplasty group (63 ± 12 years vs 60 ± 13 years, P = .02). Previous bypass operation and cardiogenic shock were equally prevalent in both groups. Baseline angiographic variables are summarized in Table II. The angioplasty group had significantly more circumflex disease (21% vs 7%, P = .0001). The stent group
.01 .0001 .006
had a significantly higher ejection fraction, 47% ± 20% for the stent group vs 42% ± 23% for the angioplasty group (P = .01). Final balloon size was used as a rough measure of vessel size. The average final balloon size was significantly larger for the stent group (3.5 ± 0.5 mm vs 3.1 ± 0.5 mm, P < .0001). This suggests that the vessels with stents were larger than the vessels subjected to angioplasty. Most lesions managed in both groups were American Heart Association/American College of Cardiology (AHA/ACC) class B. However, compared with the angioplasty group, the stent group had a greater percentage of patients with AHA/ACC class C lesions (36% vs 22%, P = .006). Although this fact is somewhat problematic in regard to comparing outcomes between the 2 groups, the higher percentage of more complex lesions in the stent group may indicate a benefit to stent implantation.
In-hospital outcomes The procedural success rate (TIMI-3 flow and residual stenosis <50%) was 100% for the stent group and 98% for
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Table III. Major clinical events Event Before discharge Deaths Acute occlusion Emergency coronary bypass operation Any event Within 6 months after procedure Death Acute occlusion Emergency coronary bypass operation Target vessel revascularization Nonfatal myocardial infarction Any event
Stent group (n = 166)
Angioplasty group (n = 212)
6 (4) 0 (0) 0 (0) 6 (4)
5 (2) 7 (3) 2 (1) 14 (7)
7 (4) 0 (0) 0 (0) 13 (8) 0 (0) 20 (12)
10 (5) 7 (3) 2 (1) 42 (20) 2 (1) 63 (30)
P Value
.55 .02 .51 .25 1.0 .02 .51 .001 .51 .00003
Values are number with percentage in parentheses.
the angioplasty group. Predischarge outcomes are shown in Table III. There were a total of 11 in-hospital deaths. Four patients from the stent group and 4 from the angioplasty group who were in a state of cardiogenic shock when they came to medical attention died of intractable shock during the hospital course. Three of the in-hospital deaths occurred among patients treated with stents after thrombolysis had failed. The other deaths occurred among patients from both groups who had undergone primary interventions for infarction (nonrescue procedures). No patient in the stent group had a sudden event suggesting acute occlusion, whereas 7 patients in the angioplasty group had acute occlusion that necessitated return to the catheterization laboratory for repeat percutaneous intervention. All these patients with acute occlusion were treated successfully with percutaneous intervention and did not need an emergency bypass operation. Of the patients who had acute reocclusion, one had been treated because of failed thrombolysis and one had undergone the infarction intervention for out-of-laboratory occlusion. Two patients in the angioplasty group underwent emergency CABG. The first patient had acute occlusion and was not re-treated in the catheterization laboratory. The second patient underwent CABG after successful percutaneous management of the culprit lesion because of the presence of multivessel disease and continued symptoms. None of the patients who underwent repeat coronary revascularization died. There was a significantly lower rate of acute occlusion after treatment in the stent group during hospitalization (0% vs 3% P = .02). In-hospital mortality did not differ significantly between the stent group and the angioplasty group (4.0% vs 2.0%). There was a significantly reduced length of stay for the stent group (5 ± 4 vs 7 ± 4 days, P < .003) (Table I).
Follow-up data Of the 358 patients discharged alive without in-hospital acute occlusion or bypass operation, 353 patients
Table IV. Cox regression analysis Variable Angioplasty Increasing age (in decades) History of diabetes Failed thrombolytic therapy History of hypertension Decreasing ejection fraction Decreasing final balloon size Vessel configuration
Risk ratio (95% CI) 2.6 (1.5-4.5) 1.0 (1.0-1.0) 1.4 (0.9-2.4) 1.6 (0.9-3.1) 1.8 (1.1-3.0) 1.0 (1.0-1.0) 1.3 (0.8-2.1) 1.0 (0.6-1.7)
P Value .0007 .88 .16 .13 .013 .32 .29 .89
(99%) participated in 6-month follow-up data collection. Major clinical events reported were death, nonfatal myocardial infarction, or target-vessel revascularization. Among patients who had more than one event during the 6 months after the procedure, only the more serious event was reported. Results of 6-month followup assessment are shown in Table III. Of the 55 patients who underwent target-vessel revascularization, 8 patients had entered the study because of failed thrombolytic therapy, and 7 of these patients were in the angioplasty group. Five of the patients who had been treated for acute infarction because of out-oflaboratory reocclusion underwent target-vessel revascularization (2 from the stent group and 3 from the angioplasty group). One death in the angioplasty group was attributed to lung carcinoma. The other deaths of members of both groups between discharge and the 6month follow-up assessment were from cardiac causes. The rate of target-vessel revascularization was significantly lower for stent implantation, 8% versus 20% (P = .001), after the procedure. Mortality did not differ significantly between the 2 groups from the time of the procedure to 6-month follow-up contact (4% vs 5%). Patients in the stent group had a significant reduction in the combined end points (death, acute reocclusion, emergency CABG, target-vessel revascularization, and
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Figure 1
Clinical events from time of procedure to 6 months after procedure. There was no significant difference between 2 groups in total mortality, rate of performance of emergency coronary bypass, and rate of nonfatal myocardial infarction. There was significantly greater proportion of acute reocclusions and target-vessel revascularizations in group who did not receive stents compared with those who did.
nonfatal myocardial infarction) from procedure to 6 months afterward compared with patients in the angioplasty group (12% vs 30%, P = .00003; Table III, Figure 1). Stent patients were free from an event significantly more so than the angioplasty group (P < .0001) (Figure 2). Possible confounding variables included in the Cox regression were age, ejection fraction, balloon size, diabetes, vessel configuration, and failed thrombolytic therapy (Table IV). Angioplasty patients were at 2.6 times greater risk for reaching an event than were stent patients. Patients with hypertension were at 1.8 times greater risk for reaching an event than were those without hypertension. No other factors were significant. There were no cerebrovascular events in either group.
Discussion Achieving and maintaining a widely patent infarctionrelated artery with TIMI-3 flow has been repeatedly shown to improve both in-hospital and long-term outcome after acute myocardial infarction.21 Primary angioplasty accomplishes this to a great extent but is still
plagued by in-hospital reocclusion and a disappointing rate of restenosis or reocclusion in the 6 months after the procedure. In the GUSTO II substudy, primary angioplasty provided a small to moderate short-term clinical advantage over thrombolytic therapy with tissue plasminogen activator when the composite end point was death, nonfatal reinfarction, and nonfatal disabling stroke. At 6-month follow-up evaluation there was no significant difference in the incidence of the composite outcome.10 The use of stents has received widespread acceptance in the management of problems other than myocardial infarction because of a significant reduction in the frequency of periprocedural acute occlusion and a documented reduction in 6-month rate of restenosis. Therefore stents would seem to be an excellent adjunct to primary angioplasty that would lead to improved early and late patency of the infarction-related vessel. The results of our study suggest these benefits can be expected in the setting of acute infarction with the same frequency as documented in the noninfarction setting. Initially the fear of acute stent thrombosis pre-
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Figure 2
Kaplan-Meier survival curves for major cardiac events (death, nonfatal myocardial infarction, acute reocclusion, emergency coronary artery bypass, and target vessel revascularization).
cluded the use of stents in vessels with a substantial thrombus burden, especially during acute myocardial infarction. Reports18,19,22,23 demonstrated this concern to be unfounded and showed that stents could be safely deployed in the acute infarction setting without the need for additional pharmacologic support. Our results supported these findings and demonstrated significant improvement in maintenance of vessel patency, according to clinical criteria, both acutely during hospitalization and at 6 month follow-up assessment.
Early reocclusion A patent infarct-related artery with brisk TIMI-3 flow is associated with a better hospital outcome, especially if this vessel remains widely patent.4 In most comparative studies this occurs among more than 90% of patients who undergo primary angioplasty compared
with the 50% to 75% of patients treated with thrombolytic therapy. Both primary angioplasty and thrombolytic therapy are associated with an appreciable inhospital reocclusion rate that affects early and late outcome. Among the 166 patients with infarction who received stents there was no clinical reocclusion of the infarction-related vessel. Stone et al22 also demonstrated a low rate of in-hospital events after primary stenting for acute myocardial infarction: reinfarction (1.7%), recurrent ischemia (3.8%), and predischarge target-vessel revascularization for ischemia (1.3%). This suggests that a powerful predictor of long-term survival after acute myocardial infarction, vessel patency at discharge, is more likely to be achieved with stenting of the infarction-related vessel. Length of hospital stay was significantly lower for the stent group (5 days), than it was for the angioplasty
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group (7 days). However, the shorter length of stay for the stent group may also be accounted for by the fact that this group was younger, had fewer patients with diabetes, and had better left ventricular function. However, the initial anticoagulation protocol with warfarin, which required in-hospital titration, may have tempered the reduction in length of stay among the stent group.
Six-month clinical follow-up findings Previous follow-up studies after primary angioplasty showed a discouragingly high restenosis rate, about 24%, and an angiographic reocclusion or restenosis rate of 40% at 6 months.8,9 This would be in keeping with previous data showing a higher restenosis rate in the presence of unstable ischemic syndromes. Thus a fractured, thrombus-containing plaque is more likely to recur when the patient is treated with balloon angioplasty alone. The significant reduction in rate of 6month events, especially target-vessel revascularization, when stents were used for primary intervention is very encouraging. This finding was reaffirmed in one small, randomized study in which stenting was compared with balloon angioplasty in the management of acute myocardial infarction.23 In that small, randomized trial, 150 patients were randomly assigned to elective stenting or no further intervention after successful primary balloon angioplasty.23 At 6 months, the incidence of the primary end point (death, reinfarction, or repeat target vessel revascularization) was 9% for the stent group and 28% for the balloon angioplasty group.23 These findings were similar to those in our study—12% for the stent group and 30% for the balloon angioplasty group.
Anticoagulation The remarkable absence of acute stent thrombosis may be attributed to the newer stent techniques of postprocedural dilation with high pressure and the compulsive use of ticlopidine and aspirin. Other techniques such as abundant use of aspirin (chewable, before intervention) and use of ionic contrast material in the care of all patients may have played a role.
Limitations of the study In this study we performed a nonrandomized comparison of stent insertion versus angioplasty in the treatment of patients with acute myocardial infarction. Therefore we could not exclude any inherent bias in either direction, although stents were used in larger arteries. Although excellent clinical follow-up assessment was conducted, there was no angiographic followup evaluation, so any silent occlusions were not detected. However, there was no reason to believe that silent occlusion would occur with any greater frequency in either group. Final balloon size was used in this series as an indirect measure of reference vessel diameter. Although final balloon size is a less than perfect substi-
tute for reference vessel size determined with quantitative coronary angiography, the choice of final balloon size in all cases was based on visual angiographic assessment of the diameter of the reference vessel. Important differences were found in the baseline characteristics of the 2 groups that may have contributed to better outcomes among the stent group, although this group had a greater percentage of patients with hypertension and type C lesions. These differences in baseline and angiographic characteristics somewhat limit the value of comparisons between the stent and angioplasty patients and underscores the need for a randomized trial.
Conclusions This study suggests that certain outcomes after acute myocardial infarction, both during hospitalization and 6 months later, may be improved with the use of stents. The main benefits achieved with the use of stents were a significant reduction in acute vessel reocclusion leading to reintervention in the hospital and a significant reduction in the need for target-vessel revascularization in the first 6 months. Two randomized trials in progress, the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) and the Randomized Trial of Primary PTCA versus Heparin Coated Stent Implantation during Acute Myocardial Infarction (STENT PAMI) are evaluating long-term outcomes of stent deployment in acute myocardial infarction.
References 1. Rothbaum DA, Linnemeier TJ, Landin RJ, Steinmetz EF, Hillis JS, Hallam CC. Emergency percutaneous transluminal coronary angioplasty in acute myocardial infarction: a 3 year experience. J Am Coll Cardiol 1987;10:264-72. 2. O’Keefe JH Jr, Rutherford BD, McConahay DR, Ligon RW, Johnson WL, Giorgi LV. Early and late results of coronary angioplasty without antecedent thrombolytic therapy for acute myocardial infarction. Am J Cardiol 1989;64:1221-30. 3. Kahn JK, Rutherford BD, McConahay DR, Johnson WL, Giorgi LV, Shimshak TM. Catheterization laboratory events and hospital outcome with direct angioplasty for acute myocardial infarction. Circulation 1990;82:1910-5. 4. Bedotto JB, Kahn JK, Rutherford BD, McConahay DR, Giorgi LV, Johnson, WL. Failed direct coronary angioplasty for acute myocardial infarction: in-hospital outcome and predictors of death. J Am Coll Cardiol 1993;22:690-4. 5. Grines CL, Browne KF, Marco J, Rothbaum D, Stone GW, O’Keefe J for the Primary Angioplasty in Myocardial Infarction Study Group. A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. N Engl J Med 1993;328:673-9. 6. Zijlstra F, de Boer MJ, Hoorntje JC, Reiffers S, Reiber JH, Suryapranata H. A comparison of immediate coronary angioplasty with intravenous streptokinase in acute myocardial infarction. N Engl J Med 1993;328:680-4. 7. Gibbons RJ, Holmes DR, Reeder GS, Bailey KR, Hopfenspirger MR, Gersh BJ. Immediate angioplasty compared with the administration of a thrombolytic agent followed by conservative treatment for myocardial infarction. N Engl J Med 1993;328:685-91.
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8. Brodie BR, Grines CL, Ivanhoe R, Knopf W, Taylor G, O’Keefe J. Six-month clinical and angiographic follow-up after direct angioplasty for acute myocardial infarction: final results from the primary angioplasty registry. Circulation 1994;25:156-62. 9. O’Neill WW, Brodie BR, Ivanhoe R, Knopf W, Taylor G, O’Keefe J. Primary coronary angioplasty for acute myocardial infarction (The Primary Angioplasty Registry). Am J Cardiol 1994;73:627-34. 10. The Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes (GUSTO IIb) Angioplasty Substudy Investigators. A clinical trial comparing primary coronary angioplasty with tissue plasminogen activator for acute myocardial infarction. N Engl J Med 1997;336:1621-8. 11. Albiero R, Hall P, Itoh A, Blengino S, Nakamura S, Martini G. Results of a consecutive series of patients receiving only antiplatelet therapy after optimized stent implantation: comparison of aspirin alone versus combined ticlopidine and aspirin therapy. Circulation 1997;95:1145-56. 12. Moussa I, DiMario C, Reimers B, Akiyama T, Tobis J, Colombo A. Subacute stent thrombosis in the era of intravascular ultrasoundguided coronary stenting without anticoagulation: frequency, predictors and clinical outcome. J Am Coll Cardiol 1997;29:6-12. 13. Nakamura S, Hall P, Gaglione A, Tiecco F, DiMaggio M, Maiello L. High pressure assisted coronary stent implantation accomplished without intravascular ultrasound guidance and subsequent anticoagulation. J Am Coll Cardiol 1997;29:21-7. 14. Versaci F, Gaspardone A, Tomai F, Crea F, Chiariello L, Gioffre PA. A comparison of coronary-artery stenting with angioplasty for isolated stenosis of the proximal left anterior descending coronary artery. N Engl J Med 1997;336:817-22 15. Serruys PW, de Jaegere P, Kiemeneij F, Macaya C, Rutsch W, Heyndrickx G for the Benestent Study Group. A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. N Engl J Med 1994; 331:489-95.
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16. Fischman DL, Leon MB, Baim DS, Schatz RA, Savage MP, Penn I for the Stent Restenosis Study Investigators. A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. N Engl J Med 1994;331:496-501. 17. Herrmann HC, Buchbinder M, Clemen MW, Fischman D, Goldberg S, Leon MB. Emergent use of balloon-expandable coronary artery stenting for failed percutaneous transluminal coronary angioplasty. Circulation 1992;86:812-9. 18. Roubin GS, Cannon AD, Agrawal SK, Macander PJ, Dean LS, BaxIey WA. Intracoronary stenting for acute and threatened closure complicating percutaneous transluminal coronary angioplasty. Circulation 1992;85:916-26. 19. Saito S, Hosokawa FG, Kim K, Tanaka S, Miyake S. Primary stent implantation without Coumadin in acute myocardial infarction. J Am Coll Cardiol 1996;28:74-81. 20. Schomig A, Neumann FJ, Walter H, Schuhlen H, Hadamitzky M, Zitzmann-Roth. Coronary stent placement in patients with acute myocardial infarction: comparison of clinical and angiographic outcome after randomization to antiplatelet or anticoagulant therapy. J Am Coll Cardiol 1997;29:28-34. 21. Simes RJ, Topol EJ, Holmes DR Jr, White HD, Rutsch WR, Vahanian A. Link between the angiographic substudy and mortality outcomes in a large randomized trial of myocardial reperfusion: importance of early and complete infarct artery reperfusion. GUSTO-I Investigators. Circulation 1995;91:1923- 8. 22. Stone GW, Brodie BR, Griffin JJ, Morice MC, Costantini C, St Goar FG. Prospective, multicenter study of the safety and feasibility of primary stenting in acute myocardial infarction: in-hospital and 30-day results of the PAMI stent pilot trial. J Am Coll Cardiol 1998:31:23-30. 23. Antoniucci D, Santoro GM, Bolognese L, Valenti R, Trapani M, Fazzini PF. A clinical trial comparing primary stenting of the infarct-related artery with optimal primary angioplasty for acute myocardial infarction: results from the Florence Randomized Elective Stenting in Acute Coronary Occlusions (FRESCO) Trial. J Am Coll Cardiol 1998;31:1234-9.
Background Compared with angioplasty, elective stent implantation has improved short-term and long-term outcome with a decrease in abrupt closure and a reduced 6-month restenosis rate. Although primary angioplasty during acute myocardial infarction has improved outcome, recurrent ischemic events and restenosis are still a problem.
Methods Outcomes for 166 consecutively treated patients who underwent stent insertion procedures within 24 hours after the onset of acute myocardial infarction were compared with those for a similar group of patients (n = 212) who underwent consecutive balloon angioplasty procedures at one tertiary care institution. The objective of this study was to examine in-hospital and late clinical outcomes for the 2 groups.
Results The procedural success rate for stenting in acute myocardial infarction was 100%; that for angioplasty was 98%. Mortality rates during hospitalization were similar for the stent group and the angioplasty group (4.0% vs 2.0%). The rate of inhospital acute reocclusion necessitating urgent percutaneous reintervention was significantly lower for the stent group (0% vs 3%, P = .02). Six months after the procedure, the stent group had a significantly lower need for revascularization of the infarctrelated artery (8% vs 20%, P = .001) and a significantly lower incidence of combined serious clinical events (death, acute occlusion, emergency bypass, target vessel revascularization, and nonfatal myocardial infarction; 12% vs 30%, P = .00003). Conclusion Compared with balloon angioplasty, stent deployment in the setting of acute myocardial infarction was associated with significantly lower frequency of in-hospital acute occlusion and significantly less need for target-vessel revascularization 6 months after myocardial infarction. (Am Heart J 2000;139:44-51.) Primary angioplasty is well documented to be an effective method for obtaining complete reperfusion (Thrombolysis in Myocardial Infarction study [TIMI-3] flow) of the infarction-related artery during an acute myocardial infarction.1,2 Despite the advantages of primary angioplasty over thrombolytic therapy, primary angioplasty is still associated with 10% to 15% risk for recurrent ischemia and reocclusion of the infarctionrelated vessel.3-7 At 6-month follow-up evaluations, rates of restenosis and reocclusion of the infarction-related artery are reported to be as high as 40%.8,9 These adverse outcomes reduce the initial advantage of primary angioplasty over thrombolytic therapy in the management of acute myocardial infarction. This effect was demonstrated in the findings of the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes study (GUSTO II).10 In that study patients who underwent angioplasty had better initial outcomes than From the Division of Cardiology, Department of Internal Medicine, North Shore University Hospital, New York University School of Medicine. Submitted June 12, 1998; accepted October 29, 1998. Reprint requests: Stanley Katz, MD, Division of Cardiology, North Shore University Hospital, 300 Community Dr, Manhasset, NY 11030. Copyright © 1999 by Mosby, Inc. 0002-8703/2000/$12.00 + 0 4/1/95494
those who underwent thrombolytic therapy. Six months after myocardial infarction, however, there was no difference in composite outcomes. Coronary stenting technique has improved, indications have expanded, and there are fewer periprocedural adverse events, such as subacute stent thrombosis.11-13 Elective coronary stenting has been reported to reduce the 6-month rate of restenosis significantly.14-16 Herrmann et al,17 however, showed that stent use in the presence of angiographically visible thrombus was a predictor of subacute stent thrombosis. Therefore it was thought that stent use was contraindicated in the setting of acute myocardial infarction in which a large thrombus burden may predispose a patient to subacute stent thrombosis. In addition to the presence of a large thrombus burden, the presence of dissection or vasospasm, reduced ejection fraction, the frequent occurrence of hypotension, and reduced coronary flow could increase risk for stent thrombosis. Roubin et al,18 in their initial experience with coil stenting after failed angioplasty (in which thrombus and dissection, as in infarction-related arteries, were prevalent) found a significant 7.6% rate of subacute stent thrombosis. Reports of newer techniques have shown primary angioplasty with stent implantation for acute myocardial infarction to be safe with low risk
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for acute thrombotic occlusion, even without the use of warfarin or concomitant intracoronary thrombolytic agents.19,20 These promising observations suggest that stent deployment during early reperfusion of an infarctrelated artery may confer added benefits over use of a balloon alone. In this study, we performed a nonrantdomized comparison of clinical outcomes to compare use of stent deployment during reperfusion of an infarctrelated artery with use of balloon angioplasty alone.
Methods Study Patients We analyzed clinical outcomes among 378 consecutively treated patients with acute myocardial infarction who came to medical attention within 24 hours after symptom onset and underwent interventions to manage the infarct. All patients treated for myocardial infarction during this time period were brought to the catheterization laboratory for possible intervention after written informed consent was obtained. The diagnosis of acute myocardial infarction was based on the typical criteria of chest pain lasting more than 30 minutes accompanied by ST-segment elevation >0.1 mV in 2 or more adjacent ECG leads. Of these patients, 166 received 1 or more intracoronary stents, and 212 underwent balloon angioplasty alone. Stents were implanted at the discretion of the interventional cardiologist. In general the decision was based on perceived ability to deliver the stent to the culprit lesion. In addition to primary infarct interventions, included in this analysis were rescue procedures on patients who had acute myocardial infarction after leaving the catheterization laboratory after elective coronary angioplasty (out-of-laboratory reocclusions). Also included were procedures on patients who had undergone unsuccessful thrombolytic therapy, generally with tissue plasminogen activator, within the previous 24 hours. Stents placed for bail-out purposes were excluded from this analysis.
Data collection In-hospital data were prospectively collected to comply with New York State mandated reporting of all coronary interventions and were available for review. The major clinical events studied during the hospitalization were acute reocclusion, death, and emergency coronary artery bypass grafting (CABG). In-hospital acute reocclusion was defined as clinically driven urgent percutaneous reintervention in the treated artery. Emergency CABG was defined as a bypass operation during hospitalization performed because of a complication from the percutaneous intervention. Six months after the procedure, information on the late clinical outcomes (death, repeat target-vessel revascularization or nonfatal myocardial infarction) were obtained through telephone contact with the patient or an immediate family member by one of the authors. Myocardial infarction was defined as an increase in serum creatine kinase level to more than twice the normal value with new pathologic Q waves. Repeat target-vessel revascularization was defined as a percutaneous coronary intervention or coronary artery bypass operation on the infarct-related vessel for relief of ischemia during the 6 months after discharge from the hospital. Death was defined as death of any cause. Cardiogenic shock in this analysis was
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defined as left ventricular filling pressure greater than 20 mm Hg and systolic blood pressure less than 90 mm Hg.
Angioplasty and stent procedure Ionic contrast material, usually a low osmolar agent (ioxaglate), was used in all instances. For stent implantation, predilation was performed in all cases with the same size balloon as the stent. The Gianturco-Roubin stent was used in 10% (17 of 166) of procedures, usually to preserve a large side branch or because of the length of the lesion. Palmaz-Schatz stents were used in 87% of procedures (145 of 166). A combination of both stents was used in 2% of the procedures (4 of 166). There were 1.3 stents used per patient. Intravascular ultrasound was not used in any procedure. All Palmaz-Schatz stents were postdilated with highpressure balloons to 14 to 18 atm. Left ventriculography was performed during the procedure, before the intervention in most cases.
Anticoagulation therapy Before the procedure, all the patients received aspirin, 975 mg, to chew. Heparin was given as a 10,000-U bolus and readministered as needed to achieve an activated clotting time of more than 300 seconds. When stents were deployed, 250 to 500 mg ticlopidine was given in most instances immediately before the procedure. Intracoronary thrombolytic agents were not given to any patient. Thirteen patients received abciximab as an adjunct to the coronary intervention (4 in the angioplasty group, 9 in the stent group, P = .09). The first 134 patients in this series received a heparin infusion that was initiated after sheath removal and lasted approximately 24 hours. For most of the other patients, heparin infusion was not initiated after the procedure because of a change in local practice. After the procedure, all patients continued aspirin indefinitely. The first 71 stent patients in the series took ticlopidine and warfarin for at least 2 weeks after the procedure. After this, stent patients took only ticlopidine for at least 2 weeks, again because of a change in local practice.
Statistical methods Time from procedure until an event (CABG or repeat intervention after discharge, death after discharge, nonfatal myocardial infarction after discharge, acute occlusion in the hospital, death in the hospital, or emergency CABG in the hospital) was analyzed with the product-limit method and the times were compared by means of the log-rank test. Baseline clinical and angiographic factors were compared between the 2 treatment groups to screen for possible confounding variables. Fisher exact and χ2 tests were used for categorical variables (sex, presence of hypertension, diabetes, smoking, or previous myocardial infarction, infarct-related artery, previous CABG, failed thrombolytic therapy, out-of-laboratory occlusion, presence of cardiogenic shock, whether treatment was within 6 hours of acute myocardial infarction, vessel configuration, and occurrence of major clinical events). The Mann-Whitney test was used for continuous variables (age, left ventricular ejection fraction, final balloon size). Factors significantly related to treatment group in the univariate analysis (P < .05) were used in a
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46 Katz et al
Table I. Clinical characteristics of 378 patients with acute myocardial infarction Characteristic Age (y) No. of men Hypertension Diabetes Smoking Previous myocardial infarction Previous bypass Unsuccessful thrombolytic therapy Abciximab therapy Out-of-laboratory reocclusion* Cardiogenic shock Time to treatment (h) <6 6–23 Length of stay (d)
Stent group (n = 166)
Angioplasty group (n = 212)
P Value
60 ± 13 120 (72) 107 (64) 23 (14) 54 (33) 30 (18) 9 (5) 32 (19) 9 (5) 4 (2) 6 (4)
63 ± 12 151 (71) 115 (54) 46 (22) 61 (29) 45 (21) 15 (7) 17 (8) 4 (2) 3 (1) 8 (4)
.02 .82 .045 .05 .43 .45 .51 .001 .09 .7 .94
130 (78) 36 (22) 5±4
170 (80) 42 (20) 7±4
.66 .003
Except for age, length of stay, and P value, all values are number with percentage in parentheses. *Patients who underwent elective procedure, left the cardiac catheterization laboratory and then within the same admission, had acute myocardial infarction with closure of the target vessel.
Table II. Angiographic characteristics of patients according to treatment group Characteristic Infarct artery (n and %) Left anterior descending Left circumflex Right Left main Vein graft LV ejection fraction (mean ± SD) Final balloon size (mm; mean ± SD) Morphologic features of lesion (n and %) ACC/AHA class B ACC/AHA class C
Stent group (n = 166)
Angioplasty group (n = 212)
P Value .0001
87 (52) 11 (7) 67 (40) 1 (1) 0 (0) 47 ± 20 3.5 ± 0.5
101 (48) 45 (21) 61 (29) 2 (1) 3 (1) 42 ± 23 3.1 ± 0.5
107 (64) 59 (36)
165 (78) 47 (22)
proportional hazards (Cox) regression analysis to examine the joint (multivariate) effects of those factors.
Results Preprocedure characteristics Between March 4, 1994, and October 31, 1996, 378 patients underwent percutaneous intervention during acute myocardial infarction. When outcomes among patients in the 2 groups were compared with respect to baseline clinical variables, differences were found (Table I). There was more hypertension in the stent group (64% vs 54%, P = .045), were more patients with diabetes in the angioplasty group (22% vs 14%, P = .05), and were more older patients in the angioplasty group (63 ± 12 years vs 60 ± 13 years, P = .02). Previous bypass operation and cardiogenic shock were equally prevalent in both groups. Baseline angiographic variables are summarized in Table II. The angioplasty group had significantly more circumflex disease (21% vs 7%, P = .0001). The stent group
.01 .0001 .006
had a significantly higher ejection fraction, 47% ± 20% for the stent group vs 42% ± 23% for the angioplasty group (P = .01). Final balloon size was used as a rough measure of vessel size. The average final balloon size was significantly larger for the stent group (3.5 ± 0.5 mm vs 3.1 ± 0.5 mm, P < .0001). This suggests that the vessels with stents were larger than the vessels subjected to angioplasty. Most lesions managed in both groups were American Heart Association/American College of Cardiology (AHA/ACC) class B. However, compared with the angioplasty group, the stent group had a greater percentage of patients with AHA/ACC class C lesions (36% vs 22%, P = .006). Although this fact is somewhat problematic in regard to comparing outcomes between the 2 groups, the higher percentage of more complex lesions in the stent group may indicate a benefit to stent implantation.
In-hospital outcomes The procedural success rate (TIMI-3 flow and residual stenosis <50%) was 100% for the stent group and 98% for
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Table III. Major clinical events Event Before discharge Deaths Acute occlusion Emergency coronary bypass operation Any event Within 6 months after procedure Death Acute occlusion Emergency coronary bypass operation Target vessel revascularization Nonfatal myocardial infarction Any event
Stent group (n = 166)
Angioplasty group (n = 212)
6 (4) 0 (0) 0 (0) 6 (4)
5 (2) 7 (3) 2 (1) 14 (7)
7 (4) 0 (0) 0 (0) 13 (8) 0 (0) 20 (12)
10 (5) 7 (3) 2 (1) 42 (20) 2 (1) 63 (30)
P Value
.55 .02 .51 .25 1.0 .02 .51 .001 .51 .00003
Values are number with percentage in parentheses.
the angioplasty group. Predischarge outcomes are shown in Table III. There were a total of 11 in-hospital deaths. Four patients from the stent group and 4 from the angioplasty group who were in a state of cardiogenic shock when they came to medical attention died of intractable shock during the hospital course. Three of the in-hospital deaths occurred among patients treated with stents after thrombolysis had failed. The other deaths occurred among patients from both groups who had undergone primary interventions for infarction (nonrescue procedures). No patient in the stent group had a sudden event suggesting acute occlusion, whereas 7 patients in the angioplasty group had acute occlusion that necessitated return to the catheterization laboratory for repeat percutaneous intervention. All these patients with acute occlusion were treated successfully with percutaneous intervention and did not need an emergency bypass operation. Of the patients who had acute reocclusion, one had been treated because of failed thrombolysis and one had undergone the infarction intervention for out-of-laboratory occlusion. Two patients in the angioplasty group underwent emergency CABG. The first patient had acute occlusion and was not re-treated in the catheterization laboratory. The second patient underwent CABG after successful percutaneous management of the culprit lesion because of the presence of multivessel disease and continued symptoms. None of the patients who underwent repeat coronary revascularization died. There was a significantly lower rate of acute occlusion after treatment in the stent group during hospitalization (0% vs 3% P = .02). In-hospital mortality did not differ significantly between the stent group and the angioplasty group (4.0% vs 2.0%). There was a significantly reduced length of stay for the stent group (5 ± 4 vs 7 ± 4 days, P < .003) (Table I).
Follow-up data Of the 358 patients discharged alive without in-hospital acute occlusion or bypass operation, 353 patients
Table IV. Cox regression analysis Variable Angioplasty Increasing age (in decades) History of diabetes Failed thrombolytic therapy History of hypertension Decreasing ejection fraction Decreasing final balloon size Vessel configuration
Risk ratio (95% CI) 2.6 (1.5-4.5) 1.0 (1.0-1.0) 1.4 (0.9-2.4) 1.6 (0.9-3.1) 1.8 (1.1-3.0) 1.0 (1.0-1.0) 1.3 (0.8-2.1) 1.0 (0.6-1.7)
P Value .0007 .88 .16 .13 .013 .32 .29 .89
(99%) participated in 6-month follow-up data collection. Major clinical events reported were death, nonfatal myocardial infarction, or target-vessel revascularization. Among patients who had more than one event during the 6 months after the procedure, only the more serious event was reported. Results of 6-month followup assessment are shown in Table III. Of the 55 patients who underwent target-vessel revascularization, 8 patients had entered the study because of failed thrombolytic therapy, and 7 of these patients were in the angioplasty group. Five of the patients who had been treated for acute infarction because of out-oflaboratory reocclusion underwent target-vessel revascularization (2 from the stent group and 3 from the angioplasty group). One death in the angioplasty group was attributed to lung carcinoma. The other deaths of members of both groups between discharge and the 6month follow-up assessment were from cardiac causes. The rate of target-vessel revascularization was significantly lower for stent implantation, 8% versus 20% (P = .001), after the procedure. Mortality did not differ significantly between the 2 groups from the time of the procedure to 6-month follow-up contact (4% vs 5%). Patients in the stent group had a significant reduction in the combined end points (death, acute reocclusion, emergency CABG, target-vessel revascularization, and
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Figure 1
Clinical events from time of procedure to 6 months after procedure. There was no significant difference between 2 groups in total mortality, rate of performance of emergency coronary bypass, and rate of nonfatal myocardial infarction. There was significantly greater proportion of acute reocclusions and target-vessel revascularizations in group who did not receive stents compared with those who did.
nonfatal myocardial infarction) from procedure to 6 months afterward compared with patients in the angioplasty group (12% vs 30%, P = .00003; Table III, Figure 1). Stent patients were free from an event significantly more so than the angioplasty group (P < .0001) (Figure 2). Possible confounding variables included in the Cox regression were age, ejection fraction, balloon size, diabetes, vessel configuration, and failed thrombolytic therapy (Table IV). Angioplasty patients were at 2.6 times greater risk for reaching an event than were stent patients. Patients with hypertension were at 1.8 times greater risk for reaching an event than were those without hypertension. No other factors were significant. There were no cerebrovascular events in either group.
Discussion Achieving and maintaining a widely patent infarctionrelated artery with TIMI-3 flow has been repeatedly shown to improve both in-hospital and long-term outcome after acute myocardial infarction.21 Primary angioplasty accomplishes this to a great extent but is still
plagued by in-hospital reocclusion and a disappointing rate of restenosis or reocclusion in the 6 months after the procedure. In the GUSTO II substudy, primary angioplasty provided a small to moderate short-term clinical advantage over thrombolytic therapy with tissue plasminogen activator when the composite end point was death, nonfatal reinfarction, and nonfatal disabling stroke. At 6-month follow-up evaluation there was no significant difference in the incidence of the composite outcome.10 The use of stents has received widespread acceptance in the management of problems other than myocardial infarction because of a significant reduction in the frequency of periprocedural acute occlusion and a documented reduction in 6-month rate of restenosis. Therefore stents would seem to be an excellent adjunct to primary angioplasty that would lead to improved early and late patency of the infarction-related vessel. The results of our study suggest these benefits can be expected in the setting of acute infarction with the same frequency as documented in the noninfarction setting. Initially the fear of acute stent thrombosis pre-
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Figure 2
Kaplan-Meier survival curves for major cardiac events (death, nonfatal myocardial infarction, acute reocclusion, emergency coronary artery bypass, and target vessel revascularization).
cluded the use of stents in vessels with a substantial thrombus burden, especially during acute myocardial infarction. Reports18,19,22,23 demonstrated this concern to be unfounded and showed that stents could be safely deployed in the acute infarction setting without the need for additional pharmacologic support. Our results supported these findings and demonstrated significant improvement in maintenance of vessel patency, according to clinical criteria, both acutely during hospitalization and at 6 month follow-up assessment.
Early reocclusion A patent infarct-related artery with brisk TIMI-3 flow is associated with a better hospital outcome, especially if this vessel remains widely patent.4 In most comparative studies this occurs among more than 90% of patients who undergo primary angioplasty compared
with the 50% to 75% of patients treated with thrombolytic therapy. Both primary angioplasty and thrombolytic therapy are associated with an appreciable inhospital reocclusion rate that affects early and late outcome. Among the 166 patients with infarction who received stents there was no clinical reocclusion of the infarction-related vessel. Stone et al22 also demonstrated a low rate of in-hospital events after primary stenting for acute myocardial infarction: reinfarction (1.7%), recurrent ischemia (3.8%), and predischarge target-vessel revascularization for ischemia (1.3%). This suggests that a powerful predictor of long-term survival after acute myocardial infarction, vessel patency at discharge, is more likely to be achieved with stenting of the infarction-related vessel. Length of hospital stay was significantly lower for the stent group (5 days), than it was for the angioplasty
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group (7 days). However, the shorter length of stay for the stent group may also be accounted for by the fact that this group was younger, had fewer patients with diabetes, and had better left ventricular function. However, the initial anticoagulation protocol with warfarin, which required in-hospital titration, may have tempered the reduction in length of stay among the stent group.
Six-month clinical follow-up findings Previous follow-up studies after primary angioplasty showed a discouragingly high restenosis rate, about 24%, and an angiographic reocclusion or restenosis rate of 40% at 6 months.8,9 This would be in keeping with previous data showing a higher restenosis rate in the presence of unstable ischemic syndromes. Thus a fractured, thrombus-containing plaque is more likely to recur when the patient is treated with balloon angioplasty alone. The significant reduction in rate of 6month events, especially target-vessel revascularization, when stents were used for primary intervention is very encouraging. This finding was reaffirmed in one small, randomized study in which stenting was compared with balloon angioplasty in the management of acute myocardial infarction.23 In that small, randomized trial, 150 patients were randomly assigned to elective stenting or no further intervention after successful primary balloon angioplasty.23 At 6 months, the incidence of the primary end point (death, reinfarction, or repeat target vessel revascularization) was 9% for the stent group and 28% for the balloon angioplasty group.23 These findings were similar to those in our study—12% for the stent group and 30% for the balloon angioplasty group.
Anticoagulation The remarkable absence of acute stent thrombosis may be attributed to the newer stent techniques of postprocedural dilation with high pressure and the compulsive use of ticlopidine and aspirin. Other techniques such as abundant use of aspirin (chewable, before intervention) and use of ionic contrast material in the care of all patients may have played a role.
Limitations of the study In this study we performed a nonrandomized comparison of stent insertion versus angioplasty in the treatment of patients with acute myocardial infarction. Therefore we could not exclude any inherent bias in either direction, although stents were used in larger arteries. Although excellent clinical follow-up assessment was conducted, there was no angiographic followup evaluation, so any silent occlusions were not detected. However, there was no reason to believe that silent occlusion would occur with any greater frequency in either group. Final balloon size was used in this series as an indirect measure of reference vessel diameter. Although final balloon size is a less than perfect substi-
tute for reference vessel size determined with quantitative coronary angiography, the choice of final balloon size in all cases was based on visual angiographic assessment of the diameter of the reference vessel. Important differences were found in the baseline characteristics of the 2 groups that may have contributed to better outcomes among the stent group, although this group had a greater percentage of patients with hypertension and type C lesions. These differences in baseline and angiographic characteristics somewhat limit the value of comparisons between the stent and angioplasty patients and underscores the need for a randomized trial.
Conclusions This study suggests that certain outcomes after acute myocardial infarction, both during hospitalization and 6 months later, may be improved with the use of stents. The main benefits achieved with the use of stents were a significant reduction in acute vessel reocclusion leading to reintervention in the hospital and a significant reduction in the need for target-vessel revascularization in the first 6 months. Two randomized trials in progress, the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) and the Randomized Trial of Primary PTCA versus Heparin Coated Stent Implantation during Acute Myocardial Infarction (STENT PAMI) are evaluating long-term outcomes of stent deployment in acute myocardial infarction.
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8. Brodie BR, Grines CL, Ivanhoe R, Knopf W, Taylor G, O’Keefe J. Six-month clinical and angiographic follow-up after direct angioplasty for acute myocardial infarction: final results from the primary angioplasty registry. Circulation 1994;25:156-62. 9. O’Neill WW, Brodie BR, Ivanhoe R, Knopf W, Taylor G, O’Keefe J. Primary coronary angioplasty for acute myocardial infarction (The Primary Angioplasty Registry). Am J Cardiol 1994;73:627-34. 10. The Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes (GUSTO IIb) Angioplasty Substudy Investigators. A clinical trial comparing primary coronary angioplasty with tissue plasminogen activator for acute myocardial infarction. N Engl J Med 1997;336:1621-8. 11. Albiero R, Hall P, Itoh A, Blengino S, Nakamura S, Martini G. Results of a consecutive series of patients receiving only antiplatelet therapy after optimized stent implantation: comparison of aspirin alone versus combined ticlopidine and aspirin therapy. Circulation 1997;95:1145-56. 12. Moussa I, DiMario C, Reimers B, Akiyama T, Tobis J, Colombo A. Subacute stent thrombosis in the era of intravascular ultrasoundguided coronary stenting without anticoagulation: frequency, predictors and clinical outcome. J Am Coll Cardiol 1997;29:6-12. 13. Nakamura S, Hall P, Gaglione A, Tiecco F, DiMaggio M, Maiello L. High pressure assisted coronary stent implantation accomplished without intravascular ultrasound guidance and subsequent anticoagulation. J Am Coll Cardiol 1997;29:21-7. 14. Versaci F, Gaspardone A, Tomai F, Crea F, Chiariello L, Gioffre PA. A comparison of coronary-artery stenting with angioplasty for isolated stenosis of the proximal left anterior descending coronary artery. N Engl J Med 1997;336:817-22 15. Serruys PW, de Jaegere P, Kiemeneij F, Macaya C, Rutsch W, Heyndrickx G for the Benestent Study Group. A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. N Engl J Med 1994; 331:489-95.
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16. Fischman DL, Leon MB, Baim DS, Schatz RA, Savage MP, Penn I for the Stent Restenosis Study Investigators. A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. N Engl J Med 1994;331:496-501. 17. Herrmann HC, Buchbinder M, Clemen MW, Fischman D, Goldberg S, Leon MB. Emergent use of balloon-expandable coronary artery stenting for failed percutaneous transluminal coronary angioplasty. Circulation 1992;86:812-9. 18. Roubin GS, Cannon AD, Agrawal SK, Macander PJ, Dean LS, BaxIey WA. Intracoronary stenting for acute and threatened closure complicating percutaneous transluminal coronary angioplasty. Circulation 1992;85:916-26. 19. Saito S, Hosokawa FG, Kim K, Tanaka S, Miyake S. Primary stent implantation without Coumadin in acute myocardial infarction. J Am Coll Cardiol 1996;28:74-81. 20. Schomig A, Neumann FJ, Walter H, Schuhlen H, Hadamitzky M, Zitzmann-Roth. Coronary stent placement in patients with acute myocardial infarction: comparison of clinical and angiographic outcome after randomization to antiplatelet or anticoagulant therapy. J Am Coll Cardiol 1997;29:28-34. 21. Simes RJ, Topol EJ, Holmes DR Jr, White HD, Rutsch WR, Vahanian A. Link between the angiographic substudy and mortality outcomes in a large randomized trial of myocardial reperfusion: importance of early and complete infarct artery reperfusion. GUSTO-I Investigators. Circulation 1995;91:1923- 8. 22. Stone GW, Brodie BR, Griffin JJ, Morice MC, Costantini C, St Goar FG. Prospective, multicenter study of the safety and feasibility of primary stenting in acute myocardial infarction: in-hospital and 30-day results of the PAMI stent pilot trial. J Am Coll Cardiol 1998:31:23-30. 23. Antoniucci D, Santoro GM, Bolognese L, Valenti R, Trapani M, Fazzini PF. A clinical trial comparing primary stenting of the infarct-related artery with optimal primary angioplasty for acute myocardial infarction: results from the Florence Randomized Elective Stenting in Acute Coronary Occlusions (FRESCO) Trial. J Am Coll Cardiol 1998;31:1234-9.