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Infarct artery reocclusion after primary angioplasty, stent placement, and thrombolytic therapy for acute myocardial infarction
Progress in Cardiology
Infarct artery reocclusion after primary angioplasty, stent placement, and thrombolytic therapy for acute myocardial infarction Stephanie H. Wilson, MBBS, FRACP, Malcolm R. Bell, MBBS, FACC, Charanjit S. Rihal, MD, FACC, Kent R. Bailey, PhD, David R. Holmes, Jr, MD, FACC, and Peter B. Berger, MD, FACC Rochester, Minn
Background The benefits of thrombolytic therapy for acute myocardial infarction (AMI) are limited by reocclusion of the infarct-related artery, which occurs in 25% to 30% of patients after successful reperfusion. The frequency of reocclusion after balloon angioplasty and stenting in this setting is less well documented. The aim of this study was to analyze the frequency and timing of reocclusion after percutaneous transluminal coronary angioplasty (PTCA) and stent placement during AMI from all available studies compared with previously published reocclusion rates after thrombolysis.
Methods and Results The previously published thrombolysis data included 4231 patients in 19 studies with ≥75 patients. Only PTCA studies with ≥50 patients and stent studies with ≥30 patients, in which routine angiographic follow-up was obtained in ≥60% of patients, were included. Ten PTCA studies with a total of 1943 patients were analyzed, with follow-up angiography in 1391 (72%). Reocclusion rates ranged from 5% to 16.7%. The stent studies included 698 patients from 7 studies, with follow-up angiography in 92%. Reocclusion rates ranged from 0% to 6%. With the use of logistic regression analysis with allowance for overdispersion, there was a significantly lower rate of reocclusion after PTCA (odds ratio, 0.38; confidence interval, 0.24 to 0.57; P < .0001) and stent placement (odds ratio, 0.11; confidence interval, 0.05 to 0.22; P < .0001) compared with thrombolysis. Reocclusion after stent placement was lower than after PTCA (odds ratio, 0.28; confidence interval, 0.13 to 0.6; P < .0001). Conclusions Reocclusion after PTCA and stent placement during AMI is less frequent than after thrombolysis. This may contribute to the superior outcome of patients treated with PTCA and stent placement in this setting. (Am Heart J 2001;141: 704-10.)
The use of thrombolytic therapy in acute myocardial infarction (AMI) reduces mortality rates and improves left ventricular function.1,2 However, the benefits of thrombolytic therapy are limited by reocclusion of the infarct-related artery, which occurs in 25% to 30% of patients after successful reperfusion.3,4 Infarct artery reocclusion after AMI increases morbidity and mortality rates and blunts myocardial salvage.5,6 Because of the limitations of thrombolytic therapy, primary percutaneous transluminal coronary angioplasty (PTCA) with and without stent placement has been used in the treatment of AMI. Trials of immediate PTCA versus thrombolysis for AMI have suggested that angioplasty is associated with a lower frequency of death and nonfatal reinfarction at 30 days and that the benefits persist for at least 1 year.7 More recently, studies have From the Division of Cardiovascular Diseases, Mayo Clinic. Submitted July 19, 2000; accepted February 9, 2001. Reprint requests: Peter B. Berger, MD, Division of Cardiovascular Diseases, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail: [email protected] Copyright © 2001 by Mosby, Inc. 0002-8703/2001/$35.00 + 0 4/1/114971 doi:10.1067/mhj.2001.114971
suggested that coronary stent placement during angioplasty may improve acute procedural success rates in the context of AMI and decrease reocclusion and other adverse events in the few months after infarction.8-10 In this study, we examined the frequency and timing of reocclusion after primary PTCA and coronary stent placement for AMI from all available studies and compared these with previously published reocclusion rates after thrombolytic therapy.11
Methods A search was performed with the MEDLINE database (from January 1966 through December 1998, in the English language) with the key words reocclusion, myocardial infarction, and either (1) angioplasty or (2) stent. The scientific session abstracts published in Circulation (1996 to 1997) and the Journal of the American College of Cardiology (1996 to 1998) were also searched. Studies were included if the entry criteria required symptoms of AMI that persisted for >30 minutes, accompanied by ST elevation of >1 mm (0.1 mV) in 2 or more contiguous electrocardiographic leads and presentation for intervention within 24 hours of the onset of symptoms. For primary PTCA, only studies with a minimum of 50 patients with ≥60% angiographic follow-up were included in the analy-
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Table I. Model with best fit, with parameter estimates and standard errors Parameter
df
Estimate
SE
Intercept Log_weeks Thrombolysis Stent THRMTIME STNTTIME THRMT_Q
1 1 1 1 1 1 1
–1.9667 0.0566 0.9857 –1.2580 –0.0395 0.5795 –0.1912
0.1702 0.0894 0.2165 0.3732 0.1800 0.3431 0.0520
χ2 133.5118 0.4011 20.7212 11.3591 0.0480 2.8531 13.5238
Pr > χ2 0.0001 0.5265 0.0001 0.0008 0.8265 0.0912 0.0002
Standard errors incorporate overdispersion parameter, which is 1.32. Reference group is PTCA; time origin is by definition 26 weeks in this model. Log_weeks is defined as log(weeks + 1) minus log(27). Its coefficient represents logistic slope of reocclusion for PTCA vs log(weeks + 1). STNTTIME represents difference between logistic time slopes for PTCA and stents. THRMTIME is difficult to interpret by itself because of quadratic time term for thrombolysis (THRMT_Q), but it must be included because of inclusion of quadratic time term. Also see text.
sis. The follow-up angiograms were required to have been performed on a routine basis rather than only when clinically indicated. For the studies in which stents were used, only studies with ≥30 patients with >60% angiographic follow-up performed on a routine basis were analyzed. Studies were excluded if thrombolysis was administered before PTCA. Studies involving both elective and bailout stenting were included. The incidence and timing of reocclusion in these studies were compared with those after thrombolytic therapy, as previously summarized.11 This analysis, reported by Verheugt et al,11 included patients from studies with at least one follow-up angiogram after the success of thrombolytic therapy was confirmed by coronary angiography. In that report, only studies with ≥75 patients were included. A total of 4231 patients were included from 19 studies; angiographic follow-up was performed at 2 different time points in 2 of the studies. There was some variability of definitions of reocclusion among the different studies. However, the majority of studies defined success of mechanical reperfusion as the achievement of a <50% residual stenosis of the infarct-related artery and Thrombolysis In Myocardial Infarction (TIMI) grade 2-3 flow. Reocclusion was defined as TIMI grade 0-1 flow on follow-up angiography.
Statistical analysis The reported reocclusion rates, number of patients in each study, and time between treatment and repeat reangiography were recorded. The numbers of patients with and without reocclusion were calculated. Logistic regressions were then performed with the frequency option of PROC GENMOD in the SAS statistical package, with reocclusion as the dependent variable. Independent variables were weeks to angiography (with a logarithmic transformation, which tends to linearize the relation to reocclusion) and two treatment dummy variables (with either thrombolysis or PTCA used as the reference treatment). In addition to analyzing the effects of treatment and time, the interactions between treatment and time were tested. These interactions allow the different treatments to have different effects on reocclusion rates over time. A nonlinear time effect was tested by adding a quadratic time term to the model. Hypothesis tests were performed to compare the 26-week reocclusion rates. This was done by modeling the time variable as log(weeks) minus log(26). Thus the treatment
parameters became the comparisons of reocclusion rates at 26 weeks. Table I shows the model with the best fit, with the parameter estimates and their standard errors. Quadratic terms were not necessary for the stent or PTCA curves, but a quadratic was necessary for the thrombolysis curve because of its early rise to a plateau. The standard errors incorporate the overdispersion parameter, which is 1.32. The reference group is PTCA, and the time origin is by definition 26 weeks in this model. Log_weeks is defined as log(weeks + 1) minus log(27). Its coefficient represents the logistic slope of reocclusion for PTCA versus log(weeks + 1). STNTTIME represents the difference between logistic time slopes for PTCA and stents. THRMTIME is difficult to interpret by itself because of the quadratic time term for thrombolysis (THRMT_Q), but it must be included because of the inclusion of the quadratic time term. Because the fit was improved with the inclusion of interactions and quadratics, it was not possible to give an overall test for one curve lying entirely above another curve. Rather we needed to test at a specific clinically meaningful time interval, which we chose to be 26 weeks. By centering the time variable at 26 weeks as above, the treatment “main effects” parameters (stents, thrombolysis) became the comparison of interest. To obtain the direct comparison of stents and thrombolysis, we fit exactly the same model, but we made thrombolysis the reference group. The curves displayed were not fit by a computer; rather they represent a “best fit” from the data from this meta-analysis and data from other studies indicating that restenosis after PTCA and stent placement had taken place within 6 months after treatment and that it is infrequent in subsequent months.
Results Primary PTCA Between 1987 and 1998, 10 studies were found that met the above inclusion criteria. Table II12-21 summarizes these studies; 1943 patients were included, with initial success rates of PTCA ranging between 80% to 97%. Among patients with a successful procedure, follow-up angiography was performed in 1391, representing 71% of included patients. Reocclusion rates of 5.0%
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Table II. Reocclusion rates after balloon angioplasty for AMI
Patients (n)
Procedural success (%)
De Boer et al12 (1995) Nakagawa et al13 (1996)
140 160
97 90
Brodie et al14 (1994) Rothbaum et al15 (1987) O’Keefe et al16 (1989) Kusachi et al17 (1992) Ribeiro et al18 (1993) Stone et al19 (1997) Rodriguez et al20 (1998) Antoniucci et al21 (1998)
271 151 500 107 50 437 52 75
– 87 94 94 80 97 94.2 100
Author/year of publication
Patients undergoing follow-up angiography (n)
Reocclusion (%)
130 137 100 64 154 85 307 92 40 330 48 68
5 12 14 14 13 9 15 15 7.5 6 16.7 16.2
92 d 21 d 4 mo 12 mo 180 d 3–6 mo 7d 30–40 d 2d Predischarge 5.6 d 6 mo
Reocclusion (%)
Time to angiography (mean)
Time to angiography (mean)
Table III. Reocclusion rates after coronary stent placement for AMI Author/year of publication
Patients (n)
Indication for stenting
Spaulding et al9 (1997)
124
Saito et al10 (1996) Antoniucci et al22 (1996)
74 31
Suboptimal result Dissection Primary stenting Residual stenosis >30% Dissection Primary Primary Primary Primary
Suryapranata et al23 (1997) Griffin et al24 (1998) Rodriguez et al20 (1998) Antoniucci et al21 (1998)
102 240 52 75
to 16.7% were documented by angiography, with the time frame of follow-up angiography between 2 days and 12 months. One study performed angiographic follow-up at 3 time points.10
Stent placement There were 7 published studies that fit the criteria outlined in the methods. Table III9,10,20-24 summarizes these studies. A total of 698 patients were included, with 686 eligible for follow-up angiography; 629 (92%) of these underwent repeat angiography at a subsequent time point. Two studies reported angiographic followup at 2 time points. Reocclusion rates ranged from 0% to 6% on follow-up angiography, ranging from 6.2 days to 7.7 months after the initial procedure.
Comparisons among treatments The previously published incidence and time course of reocclusion after thrombolytic therapy were compared with those of primary PTCA and stent placement (Figure 1). With the use of logistic regression analysis of reocclusion on log(time), there was significant lack of
Patients undergoing follow-up angiography (n) 124 95 74 48 31 102 176 52 70
0 1 1.4 1.4 3.2 1 5.6 1.9 4.3
6.2 d 6 mo 10 d 96 d 30 d 30 d 7.7 mo 6.2 d 6 mo
fit. Therefore, all models incorporated an overdispersion estimate into the standard error of parameter estimates. Within the main-effects model (ie, overall differences between treatments but no time-by-treatment interactions), there was a nonsignificantly lower rate of reocclusion after PTCA than after thrombolysis (odds ratio [OR], 0.76; confidence interval [CI], 0.53 to 1.10; P = .15). However, there was a significant interaction between time and treatment when comparing PTCA with thrombolysis, with a much greater slope with thrombolysis than with PTCA and only the thrombolysis data showing a flattening out to an asymptote. There was also significant nonlinearity, as evidenced by significant quadratic terms for the thrombolysis trials only. When these interactions and nonlinearities were included in the model and the time variable was recentered so that the main effects of the model represented the treatment contrasts at a time of 26 weeks, there was a highly significant difference between thrombolysis and PTCA, with a lower reocclusion rate at 26 weeks for PTCA (OR, 0.38; CI, 0.24 to 0.57; P < .0001). There was also a significantly lower rate of reocclusion
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Figure 1
Incidence of reocclusion after thrombolysis, PTCA, and stent placement for AMI. x-Axis represents time between initiation of thrombolytic therapy, primary PTCA, or stent placement and time of follow-up angiography. Thrombolysis vs PTCA: OR, 0.38; CI, 0.24 to 0.57; P < .0001; thrombolysis vs stent: OR, 0.11; CI, 0.05 to 0.22; P < .0001; PTCA vs stent: OR, 0.28; CI, 0.13 to 0.6; P < .0001 (modified and reproduced with permission from Verheugt et al, J Am Coll Cardiol 1996;27:768; Figure 1).
with stent placement (OR, 0.11; CI, 0.05 to 0.22; P < .0001), compared with thrombolysis. The incidence of reocclusion after stent placement was also significantly lower than after PTCA (OR, 0.28; CI, 0.14 to 0.6; P < .0001).
Discussion The widespread use of thrombolytic therapy in AMI has substantially reduced both early and late mortality rates.1 The main benefit of thrombolytic therapy results from the rapid achievement of coronary patency and limitation of infarct size. However, a drawback of thrombolytic therapy is the high rate of reocclusion of the infarct-related artery over time,5,6 reducing the benefits of early reperfusion.3 We have demonstrated a decrease in the overall incidence of reocclusion after PTCA and coronary stent placement in the setting of AMI compared with the reocclusion rate after thrombolytic therapy.
Frequency and significance of reocclusion The role of thrombosis has been well established in myocardial infarction. Although reperfusion therapy restores blood flow by dissolving fibrin in thrombus, a nidus for recurrent thrombosis remains. Multiple studies have established that the incidence of reocclusion after successful thrombolytic therapy is up to 25%
within months of AMI.5,6,25-27 Animal models of myocardial infarction and reperfusion support the importance of sustained patency of the infarct artery after myocardial infarction.4 In clinical studies, reocclusion of a previously patent artery is associated with an increased in-hospital mortality rate and is detrimental to functional long-term recovery of left ventricular function.4 Even asymptomatic reocclusion is detrimental to the recovery of left ventricular function.3,4 Therefore, the benefit of thrombolysis is primarily limited to the group of patients who have both successful initial reperfusion and persistent patency of the infarct-related artery.
Reocclusion after PTCA Multiple randomized trials have compared thrombolytic therapy with PTCA in the treatment of myocardial infarction. Many have suggested a lower rate of death and nonfatal reinfarction among PTCA-treated patients.28-30 Meta-analysis of these studies revealed a significant reduction in mortality rates with PTCA.7,31 Most of these trials did not examine the frequency of reocclusion in the months after AMI. Comparing the incidence of reocclusion after thrombolysis, as described by Verheugt et al,11 with reocclusion rates after PTCA in multiple trials, the incidence of reocclusion after angioplasty appears to be significantly lower after PTCA, perhaps contributing to the clinical benefit
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Table IV. Reocclusion rates after thrombolytic therapy for AMI Author/or study name Serruys Timmis TIMI-1 TAMI-1 Uebis-1 Uebis-2 Anderson PRIMI Ohman TAMI 1-5 TEAM-2 ARMS TAMI-7 TAPS-1 TAPS-2 HART APRICOT GUSTO TIMI-5 White TIMI-4
Patients (n) 91 95 91 197 106 76 77 213 419 607 190 102 157 339 339 98 248 586 183 154 278
Thrombolytic agent
Reocclusion (%)
Time to angiography (mean)
21 14 19 12 6 25 5 3 9 11 2 4 7 6 11 9 29 6 4 25 5
2–8 wk 10–24 d 5–25 d 7–10 d 3d 6 mo <24 h 24–36 h 7d 7–10 d 1d 24 h 5–10 d 24–48 h 14–21 d 7d 3 mo 5–7 d 16–36 h 1y 18–36 h
IC/IV SK IC SK SK/TPA TPA IC SK IC SK IC SK/APSAC Pro-UK IV UK, TPA IV UK, TPA SK, APSAC APSAC IV UK, TPA APSAC, TPA APSAC, TPA TPA SK, APSAC SK, TPA TPA SK, TPA APSAC, TPA
APSAC, Anisoylated plasminogen streptokinase activator complex; IC, intracoronary; IV, intravenous; SK, streptokinase; TPA, tissue plasminogen activator; pro-UK, prourokinase.
seen with PTCA in the randomized trials. The reocclusion rate after angioplasty at 3 to 6 months in the current study does not appear to be significantly higher than at 3 weeks, as was also demonstrated by the serial angiographic study of Nakagawa et al13 and later confirmed by others.12,15 This is in contrast to the findings after thrombolysis, with reocclusion rates of 28% at 3 months6 and 25% at 1 year26 and an increase in reocclusion rates over time in serial studies.32,33 Factors influencing the likelihood of long-term patency of the infarct artery include the degree of residual stenosis26 and whether normal antegrade blood flow was restored, both of which may be more favorably influenced by PTCA and particularly stenting compared with thrombolysis. The importance of sustained patency after AMI with mechanical reperfusion was underscored by Brodie et al,34 who demonstrated the importance of a patent infarct-related artery after PTCA to recovery of left ventricular function.
Reocclusion after stent placement Several studies have suggested a relation between the residual lumen diameter after angioplasty procedures as well as the presence of residual dissection with the risk of reocclusion.35 Both of these risk factors may be improved with coronary stent placement. Coronary stenting virtually eliminates vascular recoil and reduces angiographic evidence of dissection. A recent study21 confirmed that the majority of episodes of in-hospital recurrent ischemia after balloon angioplasty for AMI were due to occlusive
or partially occlusive dissection evident at repeat emergent coronary angiography. In the months after AMI, the larger postprocedural luminal diameter achieved with coronary stenting may also lead to lower reocclusion and restenosis rates. Coronary stenting was initially thought to be contraindicated in the presence of thrombus caused by a high incidence of stent thrombosis in such patients.36 Subsequently, several patient series have demonstrated the safety of stent placement in the presence of a large thrombus burden.37 In Table IV, the studies show a remarkably low incidence of reocclusion, significantly lower than PTCA alone, after both primary stenting and bailout stenting after suboptimal balloon angioplasty. Other potential benefits of stenting are still being studied in large, randomized trials.
Limitations The current study is not a randomized comparison of patients with AMI treated with thrombolysis, PTCA, and stent implantation but rather a meta-analysis of multiple trials and the inclusion and exclusion criteria between the studies as well as the definitions used, and study designs varied somewhat. In general, the PTCA studies included patients with a longer time from symptom onset to treatment (up to 24 hours). However, this would be expected to lead to an increased reocclusion rate in the PTCA group. The stent group was somewhat heterogeneous and included some study patients who underwent bailout stenting as well as primary stenting. However, bailout stenting would be expected to in-
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crease the incidence of reocclusion and minimize the benefit of stenting over PTCA and thrombolysis.38 One of the studies,20 included in both the PTCA and stent groups, randomly assigned patients with optimal balloon angioplasty results only. This potentially could have decreased the reocclusion rates in this particular study. However, the numbers of patients in this study were small and could not have to have significantly affected the overall results of this study. In addition, the reocclusion rates seen in this study were consistent with those in the other balloon angioplasty and stent studies included. In this study, only follow-up angiograms performed within 6 months of study entry were analyzed; restenosis occurs later than 6 months in a small minority of patients, and the frequency of late restenosis may differ between the different treatment groups. The majority of PTCA and stent studies did not use a core laboratory. There was a higher percentage of core laboratory use in the thrombolytic studies, although it was by no means universal. Because the use of a core laboratory may lead to an increase in the reported incidence of reocclusion, this may have been a potential source of bias in the analysis. It should also be noted that the stenting studies included patients with favorable anatomy for stent placement, with small, extremely tortuous, or calcified arteries excluded. This could have biased the analysis in favor of the stenting group. Only patients amenable to angioplasty and stent placement underwent these revascularization procedures, therefore selected patients were included in these studies. However, far more patients have contraindications from receiving thrombolytic therapy than from undergoing balloon angioplasty or stent placement; this would serve to bias the study against balloon angioplasty or stent placement. Regardless, the results of this study should only be applied to patients similar to those enrolled in the studies analyzed. Despite this, the results from our study document less reocclusion among patients undergoing percutaneous coronary intervention. In addition, percutaneous revascularization with stents was carried out in a more contemporary time period, and other procedural improvements could have occurred, such as the addition of more potent antiplatelet agents. The thrombolytic studies may have included centers without facilities for emergency catheterization and therefore fewer tertiary referral centers. However, it should be noted that in the OASIS registry, which examined the benefit of invasive therapies in the treatment of unstable angina, the results from hospitals with and without cardiac catheterization facilities were not significantly different.39
Conclusions Reocclusion after PTCA during AMI is less frequent than after thrombolysis and appears to be even less fre-
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quent when coronary stents are used. This potentially may contribute to the superior outcome of patients treated with PTCA and stent placement compared with thrombolytic therapy in AMI.
References 1. GUSTO Angiographic Investigators. The effects of tissue plasminogen activator, streptokinase, or both on coronary-artery patency, ventricular function, and survival after acute myocardial infarction. N Engl J Med 1993;329:1615-22. 2. ISIS-2 (Second International Study of Infarct Survival). Randomized trial of intravenous streptokinase, oral aspirin, both or neither among 17,187 cases of suspected acute myocardial infarction. Lancet 1988:349;60. 3. Ohman EM, Califf RM, Topol EJ, et al. Consequences of reocclusion after successful reperfusion therapy in acute myocardial infarction. Circulation 1990;82:781-91. 4. Nijland F, Kamp O, Verheugt FWA, et al. Long-term implications of reocclusion on left ventricular size and function after successful thrombolysis for first anterior myocardial infarction. Circulation 1997;95: 111-7. 5. Meijer A, Verheugt FWA, Werter CJPJ, et al. Aspirin versus Coumadin in the prevention of reocclusion and recurrent ischemia after successful thrombolysis: a prospective placebo-controlled angiographic study. Circulation 1993;87:1524-30. 6. Takens BH, Brugemann J, van der Meer J, et al. Reocclusion three months after successful thrombolytic treatment of acute myocardial infarction with anisoylated plasminogen streptokinase activating complex. Am J Cardiol 1990;65:1422-4. 7. Grines CL, Ellis SG, Jones M, et al. Primary coronary angioplasty vs thrombolytic therapy for acute myocardial infarction (MI): long-term follow-up of ten randomized trials. Circulation 1999;100(Suppl):S2629. 8. Steinhubl SR, Topol E. Stenting for acute myocardial infarction. Lancet 1997;350:532-3. 9. Spaulding C, Cador R, Benhamda K, et al. One-week and six-month angiographic controls of stent implantation after occlusive and nonocclusive dissection during primary balloon angioplasty for acute myocardial infarction. Am J Cardiol 1997;79:1592-5. 10. Saito S, Hosokawa G, Kim K, et al. Primary stent implantation without Coumadin in acute myocardial infarction. J Am Coll Cardiol 1996;28:74-81. 11. Verheugt FWA, Meijer A, Lagrand W, et al. Reocclusion: the flip side of thrombolysis. J Am Coll Cardiol 1996;27:766-73. 12. De Boer MJ, Reiber JHC, Suryapranata H, et al. Angiographic findings and catheterization laboratory events in patients with primary coronary angioplasty or streptokinase therapy for acute myocardial infarction. Eur Heart J 1995;16:1347-55. 13. Nakagawa Y, Iwasaki Y, Kimura T, et al. Serial angiographic follow-up after successful direct angioplasty for acute myocardial infarction. Am J Cardiol 1996;78:980-4. 14. Brodie BR, Grines CL, Ivanhoe R, et al. 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. 15. Rothbaum DA, Linnemeier TJ, Landin RJ, et al. Emergency percutaneous transluminal coronary angioplasty in acute myocardial infarction: a 3 year experience. J Am Coll Cardiol 1987;10:264-72. 16. O’Keefe JH, Rutherford BD, McConahy DR, et al. Early and late results of coronary angioplasty without antecedent thrombolytic therapy from acute myocardial infarction. Am J Cardiol 1989;64:1221-30.
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17. Kusachi S, Iwasaki K, Inoue K, et al. Emergency coronary angioplasty for acute myocardial infarction. Jpn Circ J 1992;56:871-80. 18. Ribeiro EE, Silva LA, Carneiro R, et al. Randomized trial of direct coronary angioplasty versus intravenous streptokinase in acute myocardial infarction. J Am Coll Cardiol 1993;22:376-80. 19. Stone GW, Marseles D, Brodie BR, et al. A prospective, randomized evaluation of prophylactic intraaortic balloon counterpulsation in high risk patients with acute myocardial infarction treated with primary angioplasty: Second Primary Angioplasty in Myocardial Infarction (PAMI-II) Trial Investigators. J Am Coll Cardiol 1997;29: 1459-67. 20. Rodriguez A, Bernardi V, Fernandez M, et al. In-hospital and late results of coronary stents versus conventional balloon angioplasty in acute myocardial infarction (GRAMI trial). Am J Cardiol 1998;81: 1286-91. 21. Antoniucci D, Santoro G, Bolognese L, et al. 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. 22. Antoniucci D, Valenti R, Buonamici P, et al. Direct angioplasty and stenting of the infarct-related artery in acute myocardial infarction. Am J Cardiol 1996;78:568-71. 23. Suryapranata H, Hoorntje JCA, de Boer M-J, et al. Randomized comparison of primary stenting with primary balloon angioplasty in acute myocardial infarction [abstract]. Circulation 1997;96[suppl I]:I-327. 24. Griffin J, Brodie BR, Morice M-C, et al. Incidence and predictors of angiographic restenosis and reocclusion after primary infarct stenting: core lab analysis from the PAMI stent pilot trial. J Am Coll Cardiol 1998;31(A Suppl):210A. 25. Medina A, Morales E, Hernandez E, et al. Angiographic evolution of coronary stenosis after thrombolytic therapy [abstract]. Eur Heart J 1993;14:355. 26. White HW, French JK, Brown MA, et al. Frequent reocclusion of patent infarct-related arteries between 4 weeks and 1 year: effects of antiplatelet therapy. J Am Coll Cardiol 1995;25:218-23. 27. Myears DW, Nohara R, Abendschein DR, et al. Compromise of beneficial effects of reperfusion of myocardium supplied by vessels with critical residual stenosis. J Am Coll Cardiol 1988;11:1078-86. 28. Zijlstra F, De Boer MJ, Hoorntje JCA, et al. A comparison of immediate coronary angioplasty with intravenous streptokinase in acute myocardial infarction. N Engl J Med 1993;328:680-4.
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29. Grines CL, Browne KF, Marco J, et al, 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. 30. Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO IIb) Angioplasty Substudy Investigators. A clinical trial comparing primary coronary angioplasty with tissue plasminogen activator for acute myocardia infarction. N Engl J Med 1997;336:1621-8. 31. Michels KB, Yusuf S. Does PTCA in acute myocardial infarction affect mortality and reinfarction rates? A quantitative overview (meta-analysis) of the randomized clinical trials. Circulation 1995; 91:476-85. 32. Uebis R, Dorr R, Reynen K, et al. Reokklusion nach erfolgreicher thrombolytischer Therapie beim akuten Myokardinfarkt. Klin Wochenschr 1988;66[suppl XII];115-8. 33. Neuhaus KL, Von Essen R, Tebbe U, et al. Improved thrombolysis in acute myocardial infarction with front-loaded administration of alteplase: results of the rtPA-APSAC patency study (TAPS). J Am Coll Cardiol 1992;19:885-91. 34. Brodie BR, Stuckey TD, Kissling G, et al. Importance of infarctrelated artery patency for recovery of left ventricular function and late survival after primary angioplasty for acute myocardial infarction. J Am Coll Cardiol 1996;28:319-25. 35. Ambrose JA, Almeida OD, Sharma SK, et al. Angiographic evolution of intracoronary thrombus and dissection following percutaneous transluminal coronary angioplasty in unstable angina (TAUSA) trial. Am J Cardiol 1997;79:559-63. 36. Nath C, Muller DWM, Ellis S, et al. Thrombosis of a flexible coil coronary stent: frequency, predictors and clinical outcome. J Am Coll Cardiol 1993;21:622-7. 37. Alfonso F, Rodriguez P, Phillips P, et al. Clinical and angiographic implications of coronary stenting in thrombus-containing lesions. J Am Coll Cardiol 1997;29:725-33. 38. Mahdi NA, Lopez J, Leon M, et al. Comparison of primary coronary stenting to primary balloon angioplasty with stent bailout for the treatment of patients with acute myocardial infarction. Am J Cardiol 1998;81:957-63. 39. Yusuf S, Flather M, Pogue J, et al, for the OASIS Registry Investigators. Variations between countries in invasive cardiac procedures and outcomes in patients with suspected unstable angina or myocardial infarction without initial ST elevation. Lancet 1998;352: 507-14.
Infarct artery reocclusion after primary angioplasty, stent placement, and thrombolytic therapy for acute myocardial infarction Stephanie H. Wilson, MBBS, FRACP, Malcolm R. Bell, MBBS, FACC, Charanjit S. Rihal, MD, FACC, Kent R. Bailey, PhD, David R. Holmes, Jr, MD, FACC, and Peter B. Berger, MD, FACC Rochester, Minn
Background The benefits of thrombolytic therapy for acute myocardial infarction (AMI) are limited by reocclusion of the infarct-related artery, which occurs in 25% to 30% of patients after successful reperfusion. The frequency of reocclusion after balloon angioplasty and stenting in this setting is less well documented. The aim of this study was to analyze the frequency and timing of reocclusion after percutaneous transluminal coronary angioplasty (PTCA) and stent placement during AMI from all available studies compared with previously published reocclusion rates after thrombolysis.
Methods and Results The previously published thrombolysis data included 4231 patients in 19 studies with ≥75 patients. Only PTCA studies with ≥50 patients and stent studies with ≥30 patients, in which routine angiographic follow-up was obtained in ≥60% of patients, were included. Ten PTCA studies with a total of 1943 patients were analyzed, with follow-up angiography in 1391 (72%). Reocclusion rates ranged from 5% to 16.7%. The stent studies included 698 patients from 7 studies, with follow-up angiography in 92%. Reocclusion rates ranged from 0% to 6%. With the use of logistic regression analysis with allowance for overdispersion, there was a significantly lower rate of reocclusion after PTCA (odds ratio, 0.38; confidence interval, 0.24 to 0.57; P < .0001) and stent placement (odds ratio, 0.11; confidence interval, 0.05 to 0.22; P < .0001) compared with thrombolysis. Reocclusion after stent placement was lower than after PTCA (odds ratio, 0.28; confidence interval, 0.13 to 0.6; P < .0001). Conclusions Reocclusion after PTCA and stent placement during AMI is less frequent than after thrombolysis. This may contribute to the superior outcome of patients treated with PTCA and stent placement in this setting. (Am Heart J 2001;141: 704-10.)
The use of thrombolytic therapy in acute myocardial infarction (AMI) reduces mortality rates and improves left ventricular function.1,2 However, the benefits of thrombolytic therapy are limited by reocclusion of the infarct-related artery, which occurs in 25% to 30% of patients after successful reperfusion.3,4 Infarct artery reocclusion after AMI increases morbidity and mortality rates and blunts myocardial salvage.5,6 Because of the limitations of thrombolytic therapy, primary percutaneous transluminal coronary angioplasty (PTCA) with and without stent placement has been used in the treatment of AMI. Trials of immediate PTCA versus thrombolysis for AMI have suggested that angioplasty is associated with a lower frequency of death and nonfatal reinfarction at 30 days and that the benefits persist for at least 1 year.7 More recently, studies have From the Division of Cardiovascular Diseases, Mayo Clinic. Submitted July 19, 2000; accepted February 9, 2001. Reprint requests: Peter B. Berger, MD, Division of Cardiovascular Diseases, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail: [email protected] Copyright © 2001 by Mosby, Inc. 0002-8703/2001/$35.00 + 0 4/1/114971 doi:10.1067/mhj.2001.114971
suggested that coronary stent placement during angioplasty may improve acute procedural success rates in the context of AMI and decrease reocclusion and other adverse events in the few months after infarction.8-10 In this study, we examined the frequency and timing of reocclusion after primary PTCA and coronary stent placement for AMI from all available studies and compared these with previously published reocclusion rates after thrombolytic therapy.11
Methods A search was performed with the MEDLINE database (from January 1966 through December 1998, in the English language) with the key words reocclusion, myocardial infarction, and either (1) angioplasty or (2) stent. The scientific session abstracts published in Circulation (1996 to 1997) and the Journal of the American College of Cardiology (1996 to 1998) were also searched. Studies were included if the entry criteria required symptoms of AMI that persisted for >30 minutes, accompanied by ST elevation of >1 mm (0.1 mV) in 2 or more contiguous electrocardiographic leads and presentation for intervention within 24 hours of the onset of symptoms. For primary PTCA, only studies with a minimum of 50 patients with ≥60% angiographic follow-up were included in the analy-
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Table I. Model with best fit, with parameter estimates and standard errors Parameter
df
Estimate
SE
Intercept Log_weeks Thrombolysis Stent THRMTIME STNTTIME THRMT_Q
1 1 1 1 1 1 1
–1.9667 0.0566 0.9857 –1.2580 –0.0395 0.5795 –0.1912
0.1702 0.0894 0.2165 0.3732 0.1800 0.3431 0.0520
χ2 133.5118 0.4011 20.7212 11.3591 0.0480 2.8531 13.5238
Pr > χ2 0.0001 0.5265 0.0001 0.0008 0.8265 0.0912 0.0002
Standard errors incorporate overdispersion parameter, which is 1.32. Reference group is PTCA; time origin is by definition 26 weeks in this model. Log_weeks is defined as log(weeks + 1) minus log(27). Its coefficient represents logistic slope of reocclusion for PTCA vs log(weeks + 1). STNTTIME represents difference between logistic time slopes for PTCA and stents. THRMTIME is difficult to interpret by itself because of quadratic time term for thrombolysis (THRMT_Q), but it must be included because of inclusion of quadratic time term. Also see text.
sis. The follow-up angiograms were required to have been performed on a routine basis rather than only when clinically indicated. For the studies in which stents were used, only studies with ≥30 patients with >60% angiographic follow-up performed on a routine basis were analyzed. Studies were excluded if thrombolysis was administered before PTCA. Studies involving both elective and bailout stenting were included. The incidence and timing of reocclusion in these studies were compared with those after thrombolytic therapy, as previously summarized.11 This analysis, reported by Verheugt et al,11 included patients from studies with at least one follow-up angiogram after the success of thrombolytic therapy was confirmed by coronary angiography. In that report, only studies with ≥75 patients were included. A total of 4231 patients were included from 19 studies; angiographic follow-up was performed at 2 different time points in 2 of the studies. There was some variability of definitions of reocclusion among the different studies. However, the majority of studies defined success of mechanical reperfusion as the achievement of a <50% residual stenosis of the infarct-related artery and Thrombolysis In Myocardial Infarction (TIMI) grade 2-3 flow. Reocclusion was defined as TIMI grade 0-1 flow on follow-up angiography.
Statistical analysis The reported reocclusion rates, number of patients in each study, and time between treatment and repeat reangiography were recorded. The numbers of patients with and without reocclusion were calculated. Logistic regressions were then performed with the frequency option of PROC GENMOD in the SAS statistical package, with reocclusion as the dependent variable. Independent variables were weeks to angiography (with a logarithmic transformation, which tends to linearize the relation to reocclusion) and two treatment dummy variables (with either thrombolysis or PTCA used as the reference treatment). In addition to analyzing the effects of treatment and time, the interactions between treatment and time were tested. These interactions allow the different treatments to have different effects on reocclusion rates over time. A nonlinear time effect was tested by adding a quadratic time term to the model. Hypothesis tests were performed to compare the 26-week reocclusion rates. This was done by modeling the time variable as log(weeks) minus log(26). Thus the treatment
parameters became the comparisons of reocclusion rates at 26 weeks. Table I shows the model with the best fit, with the parameter estimates and their standard errors. Quadratic terms were not necessary for the stent or PTCA curves, but a quadratic was necessary for the thrombolysis curve because of its early rise to a plateau. The standard errors incorporate the overdispersion parameter, which is 1.32. The reference group is PTCA, and the time origin is by definition 26 weeks in this model. Log_weeks is defined as log(weeks + 1) minus log(27). Its coefficient represents the logistic slope of reocclusion for PTCA versus log(weeks + 1). STNTTIME represents the difference between logistic time slopes for PTCA and stents. THRMTIME is difficult to interpret by itself because of the quadratic time term for thrombolysis (THRMT_Q), but it must be included because of the inclusion of the quadratic time term. Because the fit was improved with the inclusion of interactions and quadratics, it was not possible to give an overall test for one curve lying entirely above another curve. Rather we needed to test at a specific clinically meaningful time interval, which we chose to be 26 weeks. By centering the time variable at 26 weeks as above, the treatment “main effects” parameters (stents, thrombolysis) became the comparison of interest. To obtain the direct comparison of stents and thrombolysis, we fit exactly the same model, but we made thrombolysis the reference group. The curves displayed were not fit by a computer; rather they represent a “best fit” from the data from this meta-analysis and data from other studies indicating that restenosis after PTCA and stent placement had taken place within 6 months after treatment and that it is infrequent in subsequent months.
Results Primary PTCA Between 1987 and 1998, 10 studies were found that met the above inclusion criteria. Table II12-21 summarizes these studies; 1943 patients were included, with initial success rates of PTCA ranging between 80% to 97%. Among patients with a successful procedure, follow-up angiography was performed in 1391, representing 71% of included patients. Reocclusion rates of 5.0%
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Table II. Reocclusion rates after balloon angioplasty for AMI
Patients (n)
Procedural success (%)
De Boer et al12 (1995) Nakagawa et al13 (1996)
140 160
97 90
Brodie et al14 (1994) Rothbaum et al15 (1987) O’Keefe et al16 (1989) Kusachi et al17 (1992) Ribeiro et al18 (1993) Stone et al19 (1997) Rodriguez et al20 (1998) Antoniucci et al21 (1998)
271 151 500 107 50 437 52 75
– 87 94 94 80 97 94.2 100
Author/year of publication
Patients undergoing follow-up angiography (n)
Reocclusion (%)
130 137 100 64 154 85 307 92 40 330 48 68
5 12 14 14 13 9 15 15 7.5 6 16.7 16.2
92 d 21 d 4 mo 12 mo 180 d 3–6 mo 7d 30–40 d 2d Predischarge 5.6 d 6 mo
Reocclusion (%)
Time to angiography (mean)
Time to angiography (mean)
Table III. Reocclusion rates after coronary stent placement for AMI Author/year of publication
Patients (n)
Indication for stenting
Spaulding et al9 (1997)
124
Saito et al10 (1996) Antoniucci et al22 (1996)
74 31
Suboptimal result Dissection Primary stenting Residual stenosis >30% Dissection Primary Primary Primary Primary
Suryapranata et al23 (1997) Griffin et al24 (1998) Rodriguez et al20 (1998) Antoniucci et al21 (1998)
102 240 52 75
to 16.7% were documented by angiography, with the time frame of follow-up angiography between 2 days and 12 months. One study performed angiographic follow-up at 3 time points.10
Stent placement There were 7 published studies that fit the criteria outlined in the methods. Table III9,10,20-24 summarizes these studies. A total of 698 patients were included, with 686 eligible for follow-up angiography; 629 (92%) of these underwent repeat angiography at a subsequent time point. Two studies reported angiographic followup at 2 time points. Reocclusion rates ranged from 0% to 6% on follow-up angiography, ranging from 6.2 days to 7.7 months after the initial procedure.
Comparisons among treatments The previously published incidence and time course of reocclusion after thrombolytic therapy were compared with those of primary PTCA and stent placement (Figure 1). With the use of logistic regression analysis of reocclusion on log(time), there was significant lack of
Patients undergoing follow-up angiography (n) 124 95 74 48 31 102 176 52 70
0 1 1.4 1.4 3.2 1 5.6 1.9 4.3
6.2 d 6 mo 10 d 96 d 30 d 30 d 7.7 mo 6.2 d 6 mo
fit. Therefore, all models incorporated an overdispersion estimate into the standard error of parameter estimates. Within the main-effects model (ie, overall differences between treatments but no time-by-treatment interactions), there was a nonsignificantly lower rate of reocclusion after PTCA than after thrombolysis (odds ratio [OR], 0.76; confidence interval [CI], 0.53 to 1.10; P = .15). However, there was a significant interaction between time and treatment when comparing PTCA with thrombolysis, with a much greater slope with thrombolysis than with PTCA and only the thrombolysis data showing a flattening out to an asymptote. There was also significant nonlinearity, as evidenced by significant quadratic terms for the thrombolysis trials only. When these interactions and nonlinearities were included in the model and the time variable was recentered so that the main effects of the model represented the treatment contrasts at a time of 26 weeks, there was a highly significant difference between thrombolysis and PTCA, with a lower reocclusion rate at 26 weeks for PTCA (OR, 0.38; CI, 0.24 to 0.57; P < .0001). There was also a significantly lower rate of reocclusion
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Figure 1
Incidence of reocclusion after thrombolysis, PTCA, and stent placement for AMI. x-Axis represents time between initiation of thrombolytic therapy, primary PTCA, or stent placement and time of follow-up angiography. Thrombolysis vs PTCA: OR, 0.38; CI, 0.24 to 0.57; P < .0001; thrombolysis vs stent: OR, 0.11; CI, 0.05 to 0.22; P < .0001; PTCA vs stent: OR, 0.28; CI, 0.13 to 0.6; P < .0001 (modified and reproduced with permission from Verheugt et al, J Am Coll Cardiol 1996;27:768; Figure 1).
with stent placement (OR, 0.11; CI, 0.05 to 0.22; P < .0001), compared with thrombolysis. The incidence of reocclusion after stent placement was also significantly lower than after PTCA (OR, 0.28; CI, 0.14 to 0.6; P < .0001).
Discussion The widespread use of thrombolytic therapy in AMI has substantially reduced both early and late mortality rates.1 The main benefit of thrombolytic therapy results from the rapid achievement of coronary patency and limitation of infarct size. However, a drawback of thrombolytic therapy is the high rate of reocclusion of the infarct-related artery over time,5,6 reducing the benefits of early reperfusion.3 We have demonstrated a decrease in the overall incidence of reocclusion after PTCA and coronary stent placement in the setting of AMI compared with the reocclusion rate after thrombolytic therapy.
Frequency and significance of reocclusion The role of thrombosis has been well established in myocardial infarction. Although reperfusion therapy restores blood flow by dissolving fibrin in thrombus, a nidus for recurrent thrombosis remains. Multiple studies have established that the incidence of reocclusion after successful thrombolytic therapy is up to 25%
within months of AMI.5,6,25-27 Animal models of myocardial infarction and reperfusion support the importance of sustained patency of the infarct artery after myocardial infarction.4 In clinical studies, reocclusion of a previously patent artery is associated with an increased in-hospital mortality rate and is detrimental to functional long-term recovery of left ventricular function.4 Even asymptomatic reocclusion is detrimental to the recovery of left ventricular function.3,4 Therefore, the benefit of thrombolysis is primarily limited to the group of patients who have both successful initial reperfusion and persistent patency of the infarct-related artery.
Reocclusion after PTCA Multiple randomized trials have compared thrombolytic therapy with PTCA in the treatment of myocardial infarction. Many have suggested a lower rate of death and nonfatal reinfarction among PTCA-treated patients.28-30 Meta-analysis of these studies revealed a significant reduction in mortality rates with PTCA.7,31 Most of these trials did not examine the frequency of reocclusion in the months after AMI. Comparing the incidence of reocclusion after thrombolysis, as described by Verheugt et al,11 with reocclusion rates after PTCA in multiple trials, the incidence of reocclusion after angioplasty appears to be significantly lower after PTCA, perhaps contributing to the clinical benefit
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Table IV. Reocclusion rates after thrombolytic therapy for AMI Author/or study name Serruys Timmis TIMI-1 TAMI-1 Uebis-1 Uebis-2 Anderson PRIMI Ohman TAMI 1-5 TEAM-2 ARMS TAMI-7 TAPS-1 TAPS-2 HART APRICOT GUSTO TIMI-5 White TIMI-4
Patients (n) 91 95 91 197 106 76 77 213 419 607 190 102 157 339 339 98 248 586 183 154 278
Thrombolytic agent
Reocclusion (%)
Time to angiography (mean)
21 14 19 12 6 25 5 3 9 11 2 4 7 6 11 9 29 6 4 25 5
2–8 wk 10–24 d 5–25 d 7–10 d 3d 6 mo <24 h 24–36 h 7d 7–10 d 1d 24 h 5–10 d 24–48 h 14–21 d 7d 3 mo 5–7 d 16–36 h 1y 18–36 h
IC/IV SK IC SK SK/TPA TPA IC SK IC SK IC SK/APSAC Pro-UK IV UK, TPA IV UK, TPA SK, APSAC APSAC IV UK, TPA APSAC, TPA APSAC, TPA TPA SK, APSAC SK, TPA TPA SK, TPA APSAC, TPA
APSAC, Anisoylated plasminogen streptokinase activator complex; IC, intracoronary; IV, intravenous; SK, streptokinase; TPA, tissue plasminogen activator; pro-UK, prourokinase.
seen with PTCA in the randomized trials. The reocclusion rate after angioplasty at 3 to 6 months in the current study does not appear to be significantly higher than at 3 weeks, as was also demonstrated by the serial angiographic study of Nakagawa et al13 and later confirmed by others.12,15 This is in contrast to the findings after thrombolysis, with reocclusion rates of 28% at 3 months6 and 25% at 1 year26 and an increase in reocclusion rates over time in serial studies.32,33 Factors influencing the likelihood of long-term patency of the infarct artery include the degree of residual stenosis26 and whether normal antegrade blood flow was restored, both of which may be more favorably influenced by PTCA and particularly stenting compared with thrombolysis. The importance of sustained patency after AMI with mechanical reperfusion was underscored by Brodie et al,34 who demonstrated the importance of a patent infarct-related artery after PTCA to recovery of left ventricular function.
Reocclusion after stent placement Several studies have suggested a relation between the residual lumen diameter after angioplasty procedures as well as the presence of residual dissection with the risk of reocclusion.35 Both of these risk factors may be improved with coronary stent placement. Coronary stenting virtually eliminates vascular recoil and reduces angiographic evidence of dissection. A recent study21 confirmed that the majority of episodes of in-hospital recurrent ischemia after balloon angioplasty for AMI were due to occlusive
or partially occlusive dissection evident at repeat emergent coronary angiography. In the months after AMI, the larger postprocedural luminal diameter achieved with coronary stenting may also lead to lower reocclusion and restenosis rates. Coronary stenting was initially thought to be contraindicated in the presence of thrombus caused by a high incidence of stent thrombosis in such patients.36 Subsequently, several patient series have demonstrated the safety of stent placement in the presence of a large thrombus burden.37 In Table IV, the studies show a remarkably low incidence of reocclusion, significantly lower than PTCA alone, after both primary stenting and bailout stenting after suboptimal balloon angioplasty. Other potential benefits of stenting are still being studied in large, randomized trials.
Limitations The current study is not a randomized comparison of patients with AMI treated with thrombolysis, PTCA, and stent implantation but rather a meta-analysis of multiple trials and the inclusion and exclusion criteria between the studies as well as the definitions used, and study designs varied somewhat. In general, the PTCA studies included patients with a longer time from symptom onset to treatment (up to 24 hours). However, this would be expected to lead to an increased reocclusion rate in the PTCA group. The stent group was somewhat heterogeneous and included some study patients who underwent bailout stenting as well as primary stenting. However, bailout stenting would be expected to in-
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crease the incidence of reocclusion and minimize the benefit of stenting over PTCA and thrombolysis.38 One of the studies,20 included in both the PTCA and stent groups, randomly assigned patients with optimal balloon angioplasty results only. This potentially could have decreased the reocclusion rates in this particular study. However, the numbers of patients in this study were small and could not have to have significantly affected the overall results of this study. In addition, the reocclusion rates seen in this study were consistent with those in the other balloon angioplasty and stent studies included. In this study, only follow-up angiograms performed within 6 months of study entry were analyzed; restenosis occurs later than 6 months in a small minority of patients, and the frequency of late restenosis may differ between the different treatment groups. The majority of PTCA and stent studies did not use a core laboratory. There was a higher percentage of core laboratory use in the thrombolytic studies, although it was by no means universal. Because the use of a core laboratory may lead to an increase in the reported incidence of reocclusion, this may have been a potential source of bias in the analysis. It should also be noted that the stenting studies included patients with favorable anatomy for stent placement, with small, extremely tortuous, or calcified arteries excluded. This could have biased the analysis in favor of the stenting group. Only patients amenable to angioplasty and stent placement underwent these revascularization procedures, therefore selected patients were included in these studies. However, far more patients have contraindications from receiving thrombolytic therapy than from undergoing balloon angioplasty or stent placement; this would serve to bias the study against balloon angioplasty or stent placement. Regardless, the results of this study should only be applied to patients similar to those enrolled in the studies analyzed. Despite this, the results from our study document less reocclusion among patients undergoing percutaneous coronary intervention. In addition, percutaneous revascularization with stents was carried out in a more contemporary time period, and other procedural improvements could have occurred, such as the addition of more potent antiplatelet agents. The thrombolytic studies may have included centers without facilities for emergency catheterization and therefore fewer tertiary referral centers. However, it should be noted that in the OASIS registry, which examined the benefit of invasive therapies in the treatment of unstable angina, the results from hospitals with and without cardiac catheterization facilities were not significantly different.39
Conclusions Reocclusion after PTCA during AMI is less frequent than after thrombolysis and appears to be even less fre-
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quent when coronary stents are used. This potentially may contribute to the superior outcome of patients treated with PTCA and stent placement compared with thrombolytic therapy in AMI.
References 1. GUSTO Angiographic Investigators. The effects of tissue plasminogen activator, streptokinase, or both on coronary-artery patency, ventricular function, and survival after acute myocardial infarction. N Engl J Med 1993;329:1615-22. 2. ISIS-2 (Second International Study of Infarct Survival). Randomized trial of intravenous streptokinase, oral aspirin, both or neither among 17,187 cases of suspected acute myocardial infarction. Lancet 1988:349;60. 3. Ohman EM, Califf RM, Topol EJ, et al. Consequences of reocclusion after successful reperfusion therapy in acute myocardial infarction. Circulation 1990;82:781-91. 4. Nijland F, Kamp O, Verheugt FWA, et al. Long-term implications of reocclusion on left ventricular size and function after successful thrombolysis for first anterior myocardial infarction. Circulation 1997;95: 111-7. 5. Meijer A, Verheugt FWA, Werter CJPJ, et al. Aspirin versus Coumadin in the prevention of reocclusion and recurrent ischemia after successful thrombolysis: a prospective placebo-controlled angiographic study. Circulation 1993;87:1524-30. 6. Takens BH, Brugemann J, van der Meer J, et al. Reocclusion three months after successful thrombolytic treatment of acute myocardial infarction with anisoylated plasminogen streptokinase activating complex. Am J Cardiol 1990;65:1422-4. 7. Grines CL, Ellis SG, Jones M, et al. Primary coronary angioplasty vs thrombolytic therapy for acute myocardial infarction (MI): long-term follow-up of ten randomized trials. Circulation 1999;100(Suppl):S2629. 8. Steinhubl SR, Topol E. Stenting for acute myocardial infarction. Lancet 1997;350:532-3. 9. Spaulding C, Cador R, Benhamda K, et al. One-week and six-month angiographic controls of stent implantation after occlusive and nonocclusive dissection during primary balloon angioplasty for acute myocardial infarction. Am J Cardiol 1997;79:1592-5. 10. Saito S, Hosokawa G, Kim K, et al. Primary stent implantation without Coumadin in acute myocardial infarction. J Am Coll Cardiol 1996;28:74-81. 11. Verheugt FWA, Meijer A, Lagrand W, et al. Reocclusion: the flip side of thrombolysis. J Am Coll Cardiol 1996;27:766-73. 12. De Boer MJ, Reiber JHC, Suryapranata H, et al. Angiographic findings and catheterization laboratory events in patients with primary coronary angioplasty or streptokinase therapy for acute myocardial infarction. Eur Heart J 1995;16:1347-55. 13. Nakagawa Y, Iwasaki Y, Kimura T, et al. Serial angiographic follow-up after successful direct angioplasty for acute myocardial infarction. Am J Cardiol 1996;78:980-4. 14. Brodie BR, Grines CL, Ivanhoe R, et al. 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. 15. Rothbaum DA, Linnemeier TJ, Landin RJ, et al. Emergency percutaneous transluminal coronary angioplasty in acute myocardial infarction: a 3 year experience. J Am Coll Cardiol 1987;10:264-72. 16. O’Keefe JH, Rutherford BD, McConahy DR, et al. Early and late results of coronary angioplasty without antecedent thrombolytic therapy from acute myocardial infarction. Am J Cardiol 1989;64:1221-30.
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17. Kusachi S, Iwasaki K, Inoue K, et al. Emergency coronary angioplasty for acute myocardial infarction. Jpn Circ J 1992;56:871-80. 18. Ribeiro EE, Silva LA, Carneiro R, et al. Randomized trial of direct coronary angioplasty versus intravenous streptokinase in acute myocardial infarction. J Am Coll Cardiol 1993;22:376-80. 19. Stone GW, Marseles D, Brodie BR, et al. A prospective, randomized evaluation of prophylactic intraaortic balloon counterpulsation in high risk patients with acute myocardial infarction treated with primary angioplasty: Second Primary Angioplasty in Myocardial Infarction (PAMI-II) Trial Investigators. J Am Coll Cardiol 1997;29: 1459-67. 20. Rodriguez A, Bernardi V, Fernandez M, et al. In-hospital and late results of coronary stents versus conventional balloon angioplasty in acute myocardial infarction (GRAMI trial). Am J Cardiol 1998;81: 1286-91. 21. Antoniucci D, Santoro G, Bolognese L, et al. 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. 22. Antoniucci D, Valenti R, Buonamici P, et al. Direct angioplasty and stenting of the infarct-related artery in acute myocardial infarction. Am J Cardiol 1996;78:568-71. 23. Suryapranata H, Hoorntje JCA, de Boer M-J, et al. Randomized comparison of primary stenting with primary balloon angioplasty in acute myocardial infarction [abstract]. Circulation 1997;96[suppl I]:I-327. 24. Griffin J, Brodie BR, Morice M-C, et al. Incidence and predictors of angiographic restenosis and reocclusion after primary infarct stenting: core lab analysis from the PAMI stent pilot trial. J Am Coll Cardiol 1998;31(A Suppl):210A. 25. Medina A, Morales E, Hernandez E, et al. Angiographic evolution of coronary stenosis after thrombolytic therapy [abstract]. Eur Heart J 1993;14:355. 26. White HW, French JK, Brown MA, et al. Frequent reocclusion of patent infarct-related arteries between 4 weeks and 1 year: effects of antiplatelet therapy. J Am Coll Cardiol 1995;25:218-23. 27. Myears DW, Nohara R, Abendschein DR, et al. Compromise of beneficial effects of reperfusion of myocardium supplied by vessels with critical residual stenosis. J Am Coll Cardiol 1988;11:1078-86. 28. Zijlstra F, De Boer MJ, Hoorntje JCA, et al. A comparison of immediate coronary angioplasty with intravenous streptokinase in acute myocardial infarction. N Engl J Med 1993;328:680-4.
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29. Grines CL, Browne KF, Marco J, et al, 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. 30. Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO IIb) Angioplasty Substudy Investigators. A clinical trial comparing primary coronary angioplasty with tissue plasminogen activator for acute myocardia infarction. N Engl J Med 1997;336:1621-8. 31. Michels KB, Yusuf S. Does PTCA in acute myocardial infarction affect mortality and reinfarction rates? A quantitative overview (meta-analysis) of the randomized clinical trials. Circulation 1995; 91:476-85. 32. Uebis R, Dorr R, Reynen K, et al. Reokklusion nach erfolgreicher thrombolytischer Therapie beim akuten Myokardinfarkt. Klin Wochenschr 1988;66[suppl XII];115-8. 33. Neuhaus KL, Von Essen R, Tebbe U, et al. Improved thrombolysis in acute myocardial infarction with front-loaded administration of alteplase: results of the rtPA-APSAC patency study (TAPS). J Am Coll Cardiol 1992;19:885-91. 34. Brodie BR, Stuckey TD, Kissling G, et al. Importance of infarctrelated artery patency for recovery of left ventricular function and late survival after primary angioplasty for acute myocardial infarction. J Am Coll Cardiol 1996;28:319-25. 35. Ambrose JA, Almeida OD, Sharma SK, et al. Angiographic evolution of intracoronary thrombus and dissection following percutaneous transluminal coronary angioplasty in unstable angina (TAUSA) trial. Am J Cardiol 1997;79:559-63. 36. Nath C, Muller DWM, Ellis S, et al. Thrombosis of a flexible coil coronary stent: frequency, predictors and clinical outcome. J Am Coll Cardiol 1993;21:622-7. 37. Alfonso F, Rodriguez P, Phillips P, et al. Clinical and angiographic implications of coronary stenting in thrombus-containing lesions. J Am Coll Cardiol 1997;29:725-33. 38. Mahdi NA, Lopez J, Leon M, et al. Comparison of primary coronary stenting to primary balloon angioplasty with stent bailout for the treatment of patients with acute myocardial infarction. Am J Cardiol 1998;81:957-63. 39. Yusuf S, Flather M, Pogue J, et al, for the OASIS Registry Investigators. Variations between countries in invasive cardiac procedures and outcomes in patients with suspected unstable angina or myocardial infarction without initial ST elevation. Lancet 1998;352: 507-14.