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Safety and Benefit of Early Elective Percutaneous Coronary Intervention After Successful Thrombolytic Therapy for Acute Myocardial Infarction
Safety and Benefit of Early Elective Percutaneous Coronary Intervention After Successful Thrombolytic Therapy for Acute Myocardial Infarction Doo Sun Sim, MDa, Myung Ho Jeong, MD, PhDa,*, Youngkeun Ahn, MD, PhDa, Young Jo Kim, MD, PhDb, Shung Chull Chae, MD, PhDc, Taek Jong Hong, MD, PhDd, In Whan Seong, MD, PhDe, Jei Keon Chae, MD, PhDf, Chong Jin Kim, MD, PhDg, Myeong Chan Cho, MD, PhDh, Ki Bae Seung, MD, PhDi, Seung Jung Park, MD, PhDj, and other Korea Acute Myocardial Infarction Registry (KAMIR) Investigators The aim of this study was to assess the safety and benefits of early elective percutaneous coronary intervention (PCI) after successful thrombolytic therapy for acute myocardial infarction. Early elective PCI after successful thrombolysis is controversial, and the optimal time for PCI is elusive. Using data from the Korea Acute Myocardial Infarction Registry from November 2005 to June 2007, a total of 383 patients with acute myocardial infarction who underwent elective PCI within 2 weeks of successful thrombolytic therapy were grouped based on time between thrombolysis and PCI as group 1, <24 hours (n ⴝ 81, age 59.5 ⴞ 10.5 years, 10.9 ⴞ 7.2 hours); group 2, >24 and <48 hours (n ⴝ 79, 59.5 ⴞ 11.6 years, 36.4 ⴞ 6.8 hours); group 3, >48 hours and <72 hours (n ⴝ 79, 61.0 ⴞ 10.9 years, 59.8 ⴞ 6.8 hours); and group 4, >72 hours (n ⴝ 144, 61.7 ⴞ 12.9 years, 117.8 ⴞ 48.5 hours). Primary study outcomes included major bleeding, in-hospital death, and major adverse cardiac events (MACEs; cardiac death, myocardial infarction, repeated PCI, and coronary artery bypass surgery) at 1, 6, and 12 months. There were no differences among the 4 groups in baseline clinical characteristics and angiographic findings. There were no differences in the incidences of major bleeding, in-hospital mortality, and 1-month outcomes among groups. Rates of composite MACEs and repeated PCI at 6 and 12 months were significantly lower in patients who underwent PCI within 48 hours of thrombolytic therapy compared with those who underwent PCI later (6-month MACEs: 1.0% vs 9.5%, p ⴝ 0.014; 6-month repeated PCI: 0% vs 6.8%, p ⴝ 0.028; 12-month MACEs: 4.1% vs 14.9%, p ⴝ 0.026; 12-month repeated PCI: 1.4% vs 9.6%, p ⴝ 0.034). In conclusion, early elective PCI within 48 hours of successful thrombolytic therapy for AMI appeared safe and more beneficial compared with PCI performed later. © 2009 Elsevier Inc. (Am J Cardiol 2009;103:1333–1338)
Thrombolytic therapy is the treatment of choice for patients with ST-segment elevation myocardial infarction (STEMI) when primary percutaneous coronary intervention (PCI) is not available within 90 minutes. However, the best subsequent management of patients after thrombolytic therapy is unclear. Thus, there is obviously a need to assess the role of PCI performed at different intervals after successful thrombolytic therapy and whether an early elective ap-
a Chonnam National University Hospital, Gwangju; bYeungnam University Hospital; cKyungpook National University Hospital, Daegu; dBusan National University Hospital, Busan; eChungnam National University Hospital, Daejon; fChunbuk National University Hospital, Jeonju; gKyung Hee University Hospital, Seoul; hChungbuk National University Hospital, Cheongju; iCatholic University Hospital; and jAsan Medical Center, Seoul, Republic of Korea. Manuscript received November 14, 2008; revised manuscript received and accepted January 18, 2009. This work was supported by the Korean Circulation Society, Seoul, Korea, in commemoration of its 50th Anniversary. *Corresponding author: Tel: 82-62-220-6243; Fax: 82-62-228-7174. E-mail address: [email protected] (M.H. Jeong).
0002-9149/09/$ – see front matter © 2009 Elsevier Inc. doi:10.1016/j.amjcard.2009.01.339
proach is safe and effective in patients with acute STEMI. In the present study, we studied patients with STEMI in whom successful reperfusion of the infarct-related artery was obtained using thrombolysis followed by elective PCI and compared clinical outcomes according to time of PCI after thrombolytic therapy. Methods Consecutive patients enrolled in the Korea Acute Myocardial Infarction Registry (KAMIR; November 2005 to June 2007), a total of 383 patients with acute STEMI who underwent elective PCI within 2 weeks of successful thrombolytic therapy, were grouped based on time between thrombolysis and PCI as group 1, ⬍24 hours (n ⫽ 81, age 59.5 ⫾ 10.5 years, 10.9 ⫾ 7.2 hours); group 2, ⱖ24 and ⬍48 hours (n ⫽ 79, 59.5 ⫾ 11.6 years, 36.4 ⫾ 6.8 hours); group 3, ⱖ48 hours and ⬍72 hours (n ⫽ 79, 61.0 ⫾ 10.9 years, 59.8 ⫾ 6.8 hours); and group 4, ⬎72 hours (n ⫽ 144, 61.7 ⫾ 12.9 years, 117.8 ⫾ 48.5 hours). The KAMIR, launched in November 2005, is a population-based multicenter data collection registry evaluatwww.AJConline.org
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Table 1 Baseline clinical characteristics of the study population Variable
Time From Thrombolysis to PCI (h)
Age (yrs) Men Diabetes mellitus Hypertension Dyslipidemia Smoking Previous myocardial infarction Killip class ⱖIII on presentation Left ventricular ejection fraction Thienopyridine Glycoprotein IIb/IIIa inhibitors Symptom-to-needle time (h) Thrombolytic agent Tenecteplase Accelerated alteplase Urokinase Creatinine (mg/dl) Troponin-I (ng/ml) High-sensitivity C-reactive protein (mg/dl) N-Terminal pro-brain natriuretic peptide (pg/ml) Total cholesterol (mg/dl) Low-density lipoprotein (mg/dl) Glucose (mg/dl)
p Value
⬍24 (n ⫽ 81)
24–48 (n ⫽ 79)
48–72 (n ⫽ 79)
ⱖ72 (n ⫽ 144)
59.5 ⫾ 10.5 71 (87.7%) 20 (24.7%) 32 (39.5%) 7 (17.5%) 61 (75.3%) 2 (2.5%) 6 (7.4%) 52.4 ⫾ 11.2 30 (37.0%) 5 (6.2%) 4.0 ⫾ 3.2
59.5 ⫾ 11.6 72 (91.1%) 13 (16.5%) 31 (39.2%) 7 (21.2%) 61 (77.2%) 1 (1.3%) 3 (3.8%) 52.3 ⫾ 10.9 24 (30.4%) 1 (1.3%) 5.8 ⫾ 7.4
61.1 ⫾ 10.9 65 (82.3%) 18 (22.8%) 33 (41.8%) 8 (22.2%) 61 (77.2%) 0 (0%) 5 (6.4%) 50.3 ⫾ 9.4 21 (26.6%) 1 (1.3%) 5.5 ⫾ 9.6
61.7 ⫾ 12.9 109 (75.7%) 26 (18.1%) 63 (43.8%) 16 (30.2%) 92 (63.9%) 3 (2.1%) 8 (5.6%) 50.3 ⫾ 11.2 31 (21.5%) 3 (2.1%) 4.4 ⫾ 4.5
0.404 0.016 0.485 0.896 0.522 0.065 0.796 0.775 0.375 0.086 0.250 0.226
55 (67.9%) 21 (25.9%) 5 (6.2%) 1.1 ⫾ 0.9 80 ⫾ 114 8.5 ⫾ 31.6 1,528 ⫾ 4,824 193 ⫾ 50 122 ⫾ 40 168 ⫾ 68
46 (58.2%) 23 (29.1%) 10 (12.7%) 1.0 ⫾ 0.2 105 ⫾ 117 19.6 ⫾ 76.3 722 ⫾ 2,052 193 ⫾ 46 122 ⫾ 39 161 ⫾ 53
38 (48.1%) 34 (43.0%) 7 (8.9%) 1.0 ⫾ 0.3 108 ⫾ 295 14.6 ⫾ 66.5 865 ⫾ 2,989 187 ⫾ 40 118 ⫾ 31 184 ⫾ 69
65 (45.1%) 65 (45.1%) 14 (9.7%) 1.0 ⫾ 0.5 79 ⫾ 127 2.1 ⫾ 5.2 806 ⫾ 2,589 191 ⫾ 37 126 ⫾ 44 164 ⫾ 66
0.006 0.009 0.568 0.020 0.594 0.076 0.565 0.837 0.570 0.099
Table 2 Procedural characteristics of the study population Variable
Location of culprit lesion Left anterior descending Left circumflex Right Left main ACC/AHA lesion score A B1 B2 C Multivessel coronary disease Pre-PCI TIMI 3 Post-PCI TIMI 3 Multivessel revascularization Stent placement Drug-eluting stent Sirolimus-eluting stent Paclitaxel-eluting stent Zotarolimus-eluting stent Stent length (mm) Stent diameter (mm) No. of stents
Time From Thrombolysis to PCI (h)
p Value
⬍24 (n ⫽ 81)
24–48 (n ⫽ 79)
48–72 (n ⫽ 79)
ⱖ72 (n ⫽ 144)
29 (17.1%) 13 (16.0%) 39 (48.1%) 0
34 (43.0%) 6 (7.6%) 39 (49.4%) 0
38 (22.4%) 8 (10.1%) 33 (41.8%) 0
69 (47.9%) 14 (9.7%) 60 (41.7%) 1 (0.7%)
0.302 0.335 0.594
1 (1.2%) 15 (18.5%) 29 (35.8%) 36 (44.4%) 36 (44.4%) 34 (42.0%) 75 (93.8%) 8 (9.9%) 76 (93.8%) 71 (93.4%) 23 (32.4%) 32 (45.1%) 16 (22.5%) 25.2 ⫾ 5.7 3.3 ⫾ 0.5 1.5 ⫾ 0.8
3 (3.8%) 16 (20.3%) 36 (45.6%) 24 (30.4%) 40 (50.6%) 43 (54.4%) 76 (97.4%) 9 (11.4%) 77 (97.5%) 67 (87.0%) 28 (41.8%) 28 (41.8%) 11 (16.4%) 24.5 ⫾ 6.5 3.3 ⫾ 0.4 1.5 ⫾ 0.8
3 (3.8%) 13 (16.5%) 28 (35.4%) 35 (44.3%) 48 (60.8%) 42 (53.2%) 76 (96.2%) 12 (15.2%) 77 (97.5%) 71 (92.2%) 29 (40.8%) 30 (42.3%) 12 (16.9%) 25.2 ⫾ 6.4 3.2 ⫾ 0.4 1.6 ⫾ 0.8
6 (4.2%) 31 (21.5%) 50 (34.7%) 57 (39.6%) 70 (48.6%) 97 (67.4%) 141 (99.3%) 16 (11.1%) 139 (96.5%) 128 (92.1%) 46 (35.9%) 59 (46.1%) 23 (18.0%) 23.7 ⫾ 5.8 3.2 ⫾ 0.4 1.6 ⫾ 1.0
0.705 0.821 0.405 0.228 0.194 0.002 0.083 0.743 0.676 0.492 0.617 0.924 0.776 0.207 0.065 0.686
ACC/AHA ⫽ American College of Cardiology/American Heart Association; TIMI ⫽ Thrombolysis In Myocardial Infarction.
ing treatment practice and outcomes. The registry includes 50 community and teaching hospitals that enroll ⬎10,000 patients annually. As of August 2007, the registry contained data for 12,634 patients. The KAMIR is
supported by a research grant from the Korean Circulation Society in commemoration of its 50th anniversary and aims to improve patient care by providing greater understanding of patient management and outcomes in
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Table 3 In-hospital events and clinical outcomes at 30 days, 6 months, and 12 months Variable
Time From Thrombolysis to PCI (h)
In-hospital Death Severe bleeding 30 d after discharge Death Myocardial infarction Repeated PCI Target-vessel revascularization Coronary artery bypass grafting Total MACEs 6 mo Death Myocardial infarction Repeated PCI Target-vessel revascularization Coronary artery bypass grafting Total MACEs 12 mo Death Myocardial infarction Repeated PCI Target-vessel revascularization Coronary artery bypass grafting Total MACEs
⬍24
24–48
48–72
ⱖ72
n ⫽ 81 0 (0%) 0 (0%) n ⫽ 70 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) n ⫽ 52 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) n ⫽ 38 1 (2.6%) 0 (0%) 1 (2.6%) 1 (2.6%) 0 (0%) 2 (5.3%)
n ⫽ 79 1 (1.3%) 0 (0%) n ⫽ 67 1 (1.5%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (1.5%) n ⫽ 51 1 (2.0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (2.0%) n ⫽ 36 1 (2.8%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (2.8%)
n ⫽ 79 1 (1.3%) 1 (1.3%) n ⫽ 67 1 (1.5%) 0 (0%) 2 (2.9%) 1 (1.5%) 0 (0%) 3 (4.4%) n ⫽ 47 1 (2.1%) 0 (0%) 6 (12.8%) 5 (10.6%) 0 (0%) 7 (14.9%) n ⫽ 38 3 (7.9%) 0 (0%) 6 (15.8%) 5 (13.2%) 0 (0%) 9 (23.7%)
n ⫽ 144 0 (0%) 0 (0%) n ⫽ 124 1 (0.8%) 0 (0%) 1 (0.8%) 1 (0.8%) 0 (0%) 2 (1.6%) n ⫽ 100 3 (3.0%) 0 (0%) 4 (4.0%) 1 (1.0%) 0 (0%) 7 (7.0%) n ⫽ 76 3 (3.9%) 0 (0%) 5 (6.6%) 2 (2.6%) 0 (0%) 8 (10.5%)
Table 4 Clinical outcomes of percutaneous coronary intervention (PCI) before and after 24 hours of thrombolytic therapy
6-mo outcomes Death Repeated PCI Target-vessel revascularization Total MACEs 12-mo outcomes Death Repeated PCI Target-vessel revascularization Total MACEs
p Value
⬍24 h
ⱖ24 h
n ⫽ 52 0 (0%) 0 (0%) 0 (0%) 0 (0%) n ⫽ 38 1 (2.6%) 1 (2.6%) 1 (2.6%) 2 (5.3%)
n ⫽ 198 5 (2.5%) 10 (5.1%) 6 (3.0%) 15 (7.6%) n ⫽ 150 7 (4.7%) 11 (7.3%) 7 (4.7%) 18 (12.0%)
0.684 0.278 0.530 0.257
the rapidly evolving field of acute myocardial infarction (AMI) treatment. The diagnosis of STEMI was based on a suggestive history with ST elevation ⬎2 mm in ⱖ2 precordial leads, ST elevation ⬎1 mm in ⱖ2 limb leads, or new left branch bundle block on the 12-lead electrocardiogram with a concomitant increase in troponin-I or -T ⱖ99th percentile of the upper reference limit. Patients aged 18 to 80 years were considered eligible for thrombolytic therapy up to 12 hours from the onset of symptoms. Contraindications to thrombolytic therapy included cardiogenic shock, defined as sustained systolic blood pressure ⬍90 mm Hg with no response to fluids or systolic blood pressure ⬍100 mm Hg with vasopressor use; severe hypertension (⬎180/110 mm Hg); previous stroke; recent major surgery or trauma; prolonged cardiopulmonary resuscitation; active bleeding; oral anticoagulation with warfarin; or hemorrhagic diathesis. Varying
0.730 0.239 0.228 0.217 0.647 0.004 0.005 0.009 0.542 0.014 0.043 0.015
Table 5 Clinical outcomes of percutaneous coronary intervention (PCI) before and after 48 hours of thrombolytic therapy
p Value 0.246 0.169 0.281 0.075
0.413 0.277
6-mo outcomes Death Repeated PCI Target-vessel revascularization Total MACEs 12-mo outcomes Death Repeated PCI Target-vessel revascularization Total MACEs
⬍48 h
ⱖ48 h
n ⫽ 103 1 (1.0%) 0 (0%) 0 (0%) 1 (1.0%) n ⫽ 74 2 (2.7%) 1 (1.4%) 1 (1.4%) 3 (4.1%)
n ⫽ 147 4 (2.7%) 10 (6.8%) 6 (4.1%) 14 (9.5%) n ⫽ 114 6 (5.3%) 11 (9.6%) 7 (6.1%) 17 (14.9%)
p Value 0.344 0.028 0.031 0.014 0.384 0.034 0.039 0.026
thrombolytic regimens (urokinase, accelerated alteplase, and tenecteplase) were used during the study period. Patients underwent elective PCI within 2 weeks of successful thrombolysis after receiving loading doses of oral aspirin (300 mg) and clopidogrel (600 mg). The culprit artery underwent stent placement if the stenosis was morphologically suitable and the procedure was expected to achieve an adequate result. Nonculprit lesions underwent stent placement only if a large amount of myocardium was threatened by severe stenosis. Although administration of glycoprotein IIb/IIIa inhibitor depended on the discretion of the operator, it was usually used in interventional patients with clear angiographic evidence of thrombus. Patients who had a clear indication for urgent PCI, such as shock, persistent or recurrent chest pain, or ST-segment elevation, were excluded from the analysis. Patients who underwent a revascularization procedure as a result of failed
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Table 6 Clinical outcomes of percutaneous coronary intervention (PCI) before and after 72 hours of thrombolytic therapy
6-mo outcomes Death Repeated PCI Target-vessel revascularization Total MACEs 12-mo outcomes Death Repeated PCI Target-vessel revascularization Total MACEs
⬍72 h
ⱖ72 h
n ⫽ 142 2 (1.3) 6 (4.0) 5 (3.3) 8 (5.3) n ⫽ 112 5 (4.5) 7 (6.3) 6 (5.4) 12 (10.7)
n ⫽ 93 3 (3.0) 4 (4.0) 1 (1.0) 7 (7.0) n ⫽ 76 3 (3.9) 5 (6.6) 2 (2.6) 8 (10.5)
p Value 0.529 0.995 0.255 0.729 0.813 0.855 0.427 0.994 Figure 1. Twelve-month MACE-free survival according to PCI before and after 24 hours of thrombolytic therapy.
thrombolysis, early reinfarction, or ischemia after the initial thrombolytic therapy were also excluded. Major adverse cardiac events (MACEs) included death, myocardial infarction, and need for repeated target-vessel revascularization. Target-vessel revascularization was defined as any repeated intervention driven by lesions located in the treated vessel within and beyond the target lesion limits. Smoking was defined as any history of tobacco smoking. Hypertension was defined as a history of hypertension or antihypertensive medication use, and diabetes was defined as a history of diabetes and use of insulin or oral hypoglycemic agents on entry into the study. Hyperlipidemia was defined as a diagnosis previously made by a physician or treatment with lipid-lowering medications. Major bleeding or vascular complication was defined as any complication causing death, need for surgery or transfusion, or extended time in the hospital. Study end points were in-hospital complications, including death, myocardial infarction, bleeding complications, and the composite end point of MACEs, including death, myocardial infarction, and urgent revascularization. Clinical follow-up with respect to MACEs occurred at 30 days, 6 months, and 12 months after the baseline procedure. All statistical analyses were performed using SPSS, version 15.0 (SPSS Inc., Chicago, Illinois) for Windows (Microsoft Corp., Redmond, Washington). Continuous variables were presented as mean ⫾ SD and compared using Student’s t test (when group distributions were symmetrical and mounded) or Mann-Whitney U test (when group distributions were skewed). Chi-square test (when all expected cell counts were ⱖ5) or Fisher’s exact test (when any expected cell count was ⬍5) was used to determine the significance of differences in categorical variables. Comparisons of MACE rates among groups were adjusted on baseline variables (Table 1) using Cox proportional hazards models. All statistical tests were 2 tailed, and a p value ⬍0.05 was considered statistically significant. Results There were no differences among the 4 groups in baseline clinical characteristics (Table 1). For type of thrombolytic agent used, group 1 used mostly tenecteplase compared with group 4, which was evenly balanced. Analysis of angiographic findings showed no differences in location of
Figure 2. Twelve-month repeated PCI–free survival according to PCI before and after 24 hours of thrombolytic therapy.
Figure 3. Twelve-month MACE-free survival according to PCI before and after 48 hours of thrombolytic therapy.
culprit lesions, American College of Cardiology/American Heart Association lesion score, or prevalence of multivessel disease (Table 2). The rate of pre-PCI Thrombolysis In Myocardial Infarction grade 3 significantly increased as the interval between thrombolysis and PCI increased (p ⫽ 0.002). However, the post-PCI Thrombolysis In Myocardial Infarction grade 3 rate was not different among groups. There were no differences in the incidences of major bleeding, in-hospital mortality, and 30-day outcomes among
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tively, p ⫽ 0.014; Table 3). When patients were dichotomized according to time of PCI, such as within and after 24, 48, and 72 hours of thrombolysis, significant differences in MACEs and repeated PCI were found only between patients who underwent PCI ⬍48 hours after thrombolytic therapy and those who underwent PCI ⱖ48 hours after thrombolysis (Tables 4-6; Figures 1-6). Rates of composite MACEs and repeated PCI at 6 and 12 months were significantly lower in patients who underwent PCI within 48 hours of thrombolytic therapy compared with those who underwent PCI later (6-month MACEs: 1.0% vs 9.5%, p ⫽ 0.014; 6-month repeated PCI: 0% vs 6.8%, p ⫽ 0.028; 12-month MACEs: 4.1% vs 14.9%, p ⫽ 0.026; 12-month repeated PCI: 1.4% vs 9.6%, p ⫽ 0.034; Table 5; Figures 3 and 4). Figure 4. Twelve-month repeated PCI–free survival according to PCI before and after 48 hours of thrombolytic therapy.
Figure 5. Twelve-month MACE-free survival according to PCI before and after 72 hours of thrombolytic therapy.
Figure 6. Twelve-month repeated PCI–free survival according to PCI before and after 72 hours of thrombolytic therapy.
groups (Table 3). However, at 6 months, there were significant interactions in rates of composite MACEs and repeated PCI among groups (MACEs: 0%, 2.0%, 14.9%, and 7.0%, respectively, p ⫽ 0.009; repeated PCI: 0%, 0%, 12.8%, and 4.0%, respectively, p ⫽ 0.004; Table 3). Likewise, there were significant differences among groups in rates of composite MACEs and repeated PCI at 12 months (MACEs: 5.3%, 2.8%, 23.7%, and 10.5%, respectively, p ⫽ 0.015; repeated PCI: 2.6%, 0%, 15.8%, and 6.6%, respec-
Discussion Our results suggested that early elective PCI after successful thrombolytic therapy was safe and effective in patients with acute STEMI, especially when performed within 48 hours of thrombolysis. Early routine PCI (ⱖ24 hours) after thrombolytic therapy, rather than the traditional conservative approach of delayed and/or ischemia-guided PCI, is a controversial issue. Randomized trials during the “balloon era” found no benefit of a routine invasive strategy on clinical outcomes.1– 4 This strategy was progressively discouraged because of unsatisfactory results and unacceptable bleeding. However, recently there has been convincing evidence from several studies that PCI after successful thrombolysis for STEMI is better than no PCI or ischemia-driven PCI.5–12 These results highlight not only the effectiveness of stent placement in patients with STEMI, but also the beneficial impact of adjunctive pharmacotherapy because stent placement has not consistently been shown to reduce mortality in the setting of AMI. Although glycoprotein IIb/IIIa receptor inhibitors in combination with stent placement may be of benefit to patients with AMI, their use was highly variable and overall low in the studies of thrombolytic therapy.13–15 The combination of full-dose thrombolysis with pharmacotherapy associated with immediate PCI (1 to 3 hours) may increase the risk of bleeding, as shown in the recently halted ASsessment of the Safety and Efficacy of a New Treatment strategy with Percutaneous Coronary Intervention (ASSENT-4) trial,16 whereas routine but deferred PCI, 17 hours after thrombolysis in the Grupo de Analisis de la Cardiopatia Isquemica Aguda (GRACIA) trial, 24 hours in the Which Early ST-elevation myocardial infarction Therapy (WEST) Study, and 3 to 12 hours in GRACIA-2, was safer and reduced major bleeding complications.9,11,17 Recently, Agati et al18 also reported that early PCI (20 hours) after thrombolysis was more effective in preserving myocardial perfusion and function than thrombolysis alone. All these results show that routine but deferred PCI may be more beneficial in reducing infarct size and long-term mortality than immediate PCI.19 In the present multicenter registry experience, early elective PCI within 48 hours of thrombolytic therapy for patients with acute STEMI appeared safe and more effective compared with PCI deferred ⬎48 hours. The major benefit of the early invasive approach was a significant reduction in the need for repeated PCI. Although not fully explainable,
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the benefit of early routine PCI may be through its favorable effect in preventing additional coronary events associated with both infarcted and noninfarcted viable myocardium jeopardized by remaining ischemia, as well as in recovering and maintaining the permeability of the infarct-related artery. Regarding the optimal time for routine elective PCI, our analysis suggested that PCI be performed within 48 hours of successful thrombolytic therapy, although this warrants further validation through large randomized prospective trials. The present study was limited because of its retrospective nature and was therefore subject to the limitations pertinent to this type of clinical investigation. Patients presenting in cardiogenic shock and with in-hospital unstable clinical conditions were excluded from this study. Elderly patients (⬎80 years) were also excluded to reduce the risk of bleeding complications. It lacked systematic angiographic follow-up and quantitative coronary analysis that might affect the rate of target-vessel revascularization. Differences between the institutions involved in this research, although representative of the reality of the country’s health system, may to some extent have introduced unintentional bias. Type of thrombolytic agent used was not evenly balanced among groups. However, on multivariate analysis, this difference did not affect clinical outcomes. Regarding major bleeding, our study was not large enough to provide reliable estimates of the relative safety. Since the sample size was relatively small, results of the present study cannot necessarily be generalized to the treatment of patients with STEMI in general practice. Future large prospective studies are warranted. Acknowledgment: KAMIR Investigators: Myung Ho Jeong, MD, Young Keun Ahn, MD, Shung Chull Chae, MD, Jong Hyun Kim, MD, Seung Ho Hur, MD, Young Jo Kim, MD, In Whan Seong, MD, Dong Hoon Choi, MD, Jei Keon Chae, MD, Taek Jong Hong, MD, Jae Young Rhew, MD, Doo Il Kim, MD, In Ho Chae, MD, Jung Han Yoon, MD, Bon Kwon Koo, MD, Byung Ok Kim, MD, Myoung Yong Lee, MD, Kee Sik Kim, MD, Jin Yong Hwang, MD, Myeong Chan Cho, MD, Seok Kyu Oh, MD, Nae Hee Lee, MD, Kyoung Tae Jeong, MD, Seung Jea Tahk, MD, Jang Ho Bae, MD, Seung Woon Rha, MD, Keum Soo Park, MD, Chong Jin Kim, MD, Kyoo Rok Han, MD, Tae Hoon Ahn, MD, Moo Hyun Kim, MD, Ki Bae Seung, MD, Wook Sung Chung, MD, Ju Young Yang, MD, Chong Yun Rhim, MD, Hyeon Cheol Gwon, MD, Seong Wook Park, MD, Young Youp Koh, MD, Seung Jae Joo, MD, Soo Joong Kim, MD, Dong Kyu Jin, MD, Jin Man Cho, MD, Yang Soo Jang, MD, Jeong Gwan Cho, MD, and Seung Jung Park, MD. 1. Topol EJ, O’Neill WW, Langburd AB, Walton JA Jr., Bourdillon PD, Bates ER, Grines CL, Schork AM, Kline E, Pitt B. A randomized, placebo-controlled trial of intravenous recombinant tissue-type plasminogen activator and emergency coronary angioplasty in patients with acute myocardial infarction. Circulation 1987;75:420 – 428. 2. Belenkie I, Knudtson ML, Roth DL, Hansen JL, Traboulsi M, Hall CA, Manyari D, Filipchuck NG, Schnurr LP, Rosenal TW. Relation between flow grade after thrombolytic therapy and the effect of angioplasty on left ventricular function: a prospective randomized trial. Am Heart J 1991;121:407– 416. 3. The TIMI Research Group. Immediate versus delayed catheterization and angioplasty following thrombolytic therapy for acute myocardial infarction: TIMI II-A results. JAMA 1988;260:2849 –2858.
4. Michels KB, Yusuf S. Does PTCA in acute myocardial infarction affect mortality and reinfarction rates? A quantitative overview (metaanalysis) of the randomized clinical trials. Circulation 1995;91:476 – 485. 5. Le May MR, Wells GA, Labinaz M, Davies RF, Turek M, Leddy D, Maloney J, McKibbin T, Quinn B, Beanlands RS, et al. COMBINED ANgioplasty and Pharmacological Intervention vs Thrombolysis ALone in acute myocardial infarction (CAPITAL AMI study). J Am Coll Cardiol 2005;46:417– 424. 6. McClelland AJ, Owens CG, Walsh SJ, McCarty D, Mathew T, Stevenson M, Gracey H, Khan MM, Adgey AA. Percutaneous coronary intervention and 1 year survival in patients treated with fibrinolytic therapy for acute ST-elevation myocardial infarction. Eur Heart J 2005;26:544 –548. 7. Gibson CM, Karha J, Murphy SA, James D, Morrow DA, Cannon CP, Giugliano RP, Antman EM, Braunwald E; TIMI Study Group. Early and long-term clinical outcomes associated with reinfarction following fibrinolytic administration in the thrombolysis in myocardial infarction trials. J Am Coll Cardiol 2003;42:7–16. 8. Scheller B, Hennen B, Hammer B, Walle J, Hofer C, Hilpert V, Winter H, Nickenig G, Böhm M; SIAM III Study Group. Beneficial effects of immediate stenting after thrombolysis in acute myocardial infarction. J Am Coll Cardiol 2003;42:634 – 641. 9. Fernandez-Avilés F, Alonso JJ, Castro-Beiras A, Vázquez N, Blanco J, Alonso-Briales J, López-Mesa J, Fernández-Vazquez F, Calvo I, Martínez-Elbal L, San Román JA, Ramos B; GRACIA Group. Routine invasive strategy within 24 hours after thrombolysis versus ischaemiaguided conservative approach for acute myocardial infarction with ST-segment elevation (GRACIA-1): a randomized controlled trial. Lancet 2004;363:1045–1053. 10. Steg PG, Bonnefoy E, Chabaud S, Lapostolle F, Dubien PY, Cristofini P, Leizorovicz A, Touboul P; Comparison of Angioplasty and Prehospital Thrombolysis In acute Myocardial infarction (CAPTIM) Investigators. Impact of time to treatment on mortality after prehospital fibrinolysisor primary angioplasty: data from CAPTIM randomized clinical trial. Circulation 2003;108:2851–2856. 11. Armstrong PW; WEST Steering Committee. A comparison of pharmacologic therapy with/without timely coronary intervention vs primary percutaneous intervention early after ST-elevation myocardial infarction: the WEST (Which Early ST-elevation myocardial infarction Therapy) Study. Eur Heart J 2006;27:1530 –1538. 12. Collet JP, Montalescot G, Le May M, Borentain M, Gershlick A. Percutaneous coronary intervention after fibrinolysis. A multiple meta-analysis approach to the type of strategy. J Am Coll Cardiol 2006;48:1326 –1335. 13. De Luca G, Suryapranata H, Stone GW, Antoniucci D, Tcheng JE, Neumann FJ, Van de Werf F, Antman EM, Topol EJ. Abciximab as adjunctive therapy to reperfusion in acute ST-segment elevation myocardial infarction. A meta-analysis of randomized trials. JAMA 2005; 293:1759 –1765. 14. Montalescot G, Borentain M, Payot L, Collet JP, Thomas D. Early vs late administration of glycoprotein IIb/IIIa inhibitors in primary percutaneous coronary intervention of acute ST-segment elevation myocardial infarction: a meta-analysis. JAMA 2004;292:362–366. 15. Topol EJ, Neumann FJ, Montalescot G. A preferred reperfusion strategy for acute myocardial infarction. J Am Coll Cardiol 2003;342:1186–1189. 16. Assessment of the Safety and Efficacy of a New Treatment strategy with Percutaneous Coronary Intervention (ASSENT-4 PCI) Investigators. Primary vs tenecteplase-facilitated percutaneous coronary intervention in patients with ST-segment elevation acute myocardial infarction (ASSENT-4 PCI): randomized trial. Lancet 2006;367:569 –578. 17. Fernandez-Aviles F, Alonso JJ, Pena G, Blanco J, Alonso-Briales J, López-Mesa J, Fernández-Vázquez F, Moreu J, Hernández RA, Castro-Beiras A, et al; GRACIA-2 Investigators. Primary angioplasty vs early routine post-fibrinolysis angioplasty for acute myocardial infarction with ST-segment elevation: the GRACIA 2 non-inferiority, randomized, controlled trial. Eur Heart J 2007;28:949 –960. 18. Agati L, Funaro S, Madonna M, Sardella G, Garramone B, Galiuto L. Does coronary angioplasty after timely thrombolysis improve microvascular perfusion and left ventricular function after acute myocardial infarction? Am Heart J 2007;154:151–157. 19. Verheugt FWA. Lyse now, stent later: the grace of GRACIA. Lancet 2004;364:1014 –1015.
Thrombolytic therapy is the treatment of choice for patients with ST-segment elevation myocardial infarction (STEMI) when primary percutaneous coronary intervention (PCI) is not available within 90 minutes. However, the best subsequent management of patients after thrombolytic therapy is unclear. Thus, there is obviously a need to assess the role of PCI performed at different intervals after successful thrombolytic therapy and whether an early elective ap-
a Chonnam National University Hospital, Gwangju; bYeungnam University Hospital; cKyungpook National University Hospital, Daegu; dBusan National University Hospital, Busan; eChungnam National University Hospital, Daejon; fChunbuk National University Hospital, Jeonju; gKyung Hee University Hospital, Seoul; hChungbuk National University Hospital, Cheongju; iCatholic University Hospital; and jAsan Medical Center, Seoul, Republic of Korea. Manuscript received November 14, 2008; revised manuscript received and accepted January 18, 2009. This work was supported by the Korean Circulation Society, Seoul, Korea, in commemoration of its 50th Anniversary. *Corresponding author: Tel: 82-62-220-6243; Fax: 82-62-228-7174. E-mail address: [email protected] (M.H. Jeong).
0002-9149/09/$ – see front matter © 2009 Elsevier Inc. doi:10.1016/j.amjcard.2009.01.339
proach is safe and effective in patients with acute STEMI. In the present study, we studied patients with STEMI in whom successful reperfusion of the infarct-related artery was obtained using thrombolysis followed by elective PCI and compared clinical outcomes according to time of PCI after thrombolytic therapy. Methods Consecutive patients enrolled in the Korea Acute Myocardial Infarction Registry (KAMIR; November 2005 to June 2007), a total of 383 patients with acute STEMI who underwent elective PCI within 2 weeks of successful thrombolytic therapy, were grouped based on time between thrombolysis and PCI as group 1, ⬍24 hours (n ⫽ 81, age 59.5 ⫾ 10.5 years, 10.9 ⫾ 7.2 hours); group 2, ⱖ24 and ⬍48 hours (n ⫽ 79, 59.5 ⫾ 11.6 years, 36.4 ⫾ 6.8 hours); group 3, ⱖ48 hours and ⬍72 hours (n ⫽ 79, 61.0 ⫾ 10.9 years, 59.8 ⫾ 6.8 hours); and group 4, ⬎72 hours (n ⫽ 144, 61.7 ⫾ 12.9 years, 117.8 ⫾ 48.5 hours). The KAMIR, launched in November 2005, is a population-based multicenter data collection registry evaluatwww.AJConline.org
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Table 1 Baseline clinical characteristics of the study population Variable
Time From Thrombolysis to PCI (h)
Age (yrs) Men Diabetes mellitus Hypertension Dyslipidemia Smoking Previous myocardial infarction Killip class ⱖIII on presentation Left ventricular ejection fraction Thienopyridine Glycoprotein IIb/IIIa inhibitors Symptom-to-needle time (h) Thrombolytic agent Tenecteplase Accelerated alteplase Urokinase Creatinine (mg/dl) Troponin-I (ng/ml) High-sensitivity C-reactive protein (mg/dl) N-Terminal pro-brain natriuretic peptide (pg/ml) Total cholesterol (mg/dl) Low-density lipoprotein (mg/dl) Glucose (mg/dl)
p Value
⬍24 (n ⫽ 81)
24–48 (n ⫽ 79)
48–72 (n ⫽ 79)
ⱖ72 (n ⫽ 144)
59.5 ⫾ 10.5 71 (87.7%) 20 (24.7%) 32 (39.5%) 7 (17.5%) 61 (75.3%) 2 (2.5%) 6 (7.4%) 52.4 ⫾ 11.2 30 (37.0%) 5 (6.2%) 4.0 ⫾ 3.2
59.5 ⫾ 11.6 72 (91.1%) 13 (16.5%) 31 (39.2%) 7 (21.2%) 61 (77.2%) 1 (1.3%) 3 (3.8%) 52.3 ⫾ 10.9 24 (30.4%) 1 (1.3%) 5.8 ⫾ 7.4
61.1 ⫾ 10.9 65 (82.3%) 18 (22.8%) 33 (41.8%) 8 (22.2%) 61 (77.2%) 0 (0%) 5 (6.4%) 50.3 ⫾ 9.4 21 (26.6%) 1 (1.3%) 5.5 ⫾ 9.6
61.7 ⫾ 12.9 109 (75.7%) 26 (18.1%) 63 (43.8%) 16 (30.2%) 92 (63.9%) 3 (2.1%) 8 (5.6%) 50.3 ⫾ 11.2 31 (21.5%) 3 (2.1%) 4.4 ⫾ 4.5
0.404 0.016 0.485 0.896 0.522 0.065 0.796 0.775 0.375 0.086 0.250 0.226
55 (67.9%) 21 (25.9%) 5 (6.2%) 1.1 ⫾ 0.9 80 ⫾ 114 8.5 ⫾ 31.6 1,528 ⫾ 4,824 193 ⫾ 50 122 ⫾ 40 168 ⫾ 68
46 (58.2%) 23 (29.1%) 10 (12.7%) 1.0 ⫾ 0.2 105 ⫾ 117 19.6 ⫾ 76.3 722 ⫾ 2,052 193 ⫾ 46 122 ⫾ 39 161 ⫾ 53
38 (48.1%) 34 (43.0%) 7 (8.9%) 1.0 ⫾ 0.3 108 ⫾ 295 14.6 ⫾ 66.5 865 ⫾ 2,989 187 ⫾ 40 118 ⫾ 31 184 ⫾ 69
65 (45.1%) 65 (45.1%) 14 (9.7%) 1.0 ⫾ 0.5 79 ⫾ 127 2.1 ⫾ 5.2 806 ⫾ 2,589 191 ⫾ 37 126 ⫾ 44 164 ⫾ 66
0.006 0.009 0.568 0.020 0.594 0.076 0.565 0.837 0.570 0.099
Table 2 Procedural characteristics of the study population Variable
Location of culprit lesion Left anterior descending Left circumflex Right Left main ACC/AHA lesion score A B1 B2 C Multivessel coronary disease Pre-PCI TIMI 3 Post-PCI TIMI 3 Multivessel revascularization Stent placement Drug-eluting stent Sirolimus-eluting stent Paclitaxel-eluting stent Zotarolimus-eluting stent Stent length (mm) Stent diameter (mm) No. of stents
Time From Thrombolysis to PCI (h)
p Value
⬍24 (n ⫽ 81)
24–48 (n ⫽ 79)
48–72 (n ⫽ 79)
ⱖ72 (n ⫽ 144)
29 (17.1%) 13 (16.0%) 39 (48.1%) 0
34 (43.0%) 6 (7.6%) 39 (49.4%) 0
38 (22.4%) 8 (10.1%) 33 (41.8%) 0
69 (47.9%) 14 (9.7%) 60 (41.7%) 1 (0.7%)
0.302 0.335 0.594
1 (1.2%) 15 (18.5%) 29 (35.8%) 36 (44.4%) 36 (44.4%) 34 (42.0%) 75 (93.8%) 8 (9.9%) 76 (93.8%) 71 (93.4%) 23 (32.4%) 32 (45.1%) 16 (22.5%) 25.2 ⫾ 5.7 3.3 ⫾ 0.5 1.5 ⫾ 0.8
3 (3.8%) 16 (20.3%) 36 (45.6%) 24 (30.4%) 40 (50.6%) 43 (54.4%) 76 (97.4%) 9 (11.4%) 77 (97.5%) 67 (87.0%) 28 (41.8%) 28 (41.8%) 11 (16.4%) 24.5 ⫾ 6.5 3.3 ⫾ 0.4 1.5 ⫾ 0.8
3 (3.8%) 13 (16.5%) 28 (35.4%) 35 (44.3%) 48 (60.8%) 42 (53.2%) 76 (96.2%) 12 (15.2%) 77 (97.5%) 71 (92.2%) 29 (40.8%) 30 (42.3%) 12 (16.9%) 25.2 ⫾ 6.4 3.2 ⫾ 0.4 1.6 ⫾ 0.8
6 (4.2%) 31 (21.5%) 50 (34.7%) 57 (39.6%) 70 (48.6%) 97 (67.4%) 141 (99.3%) 16 (11.1%) 139 (96.5%) 128 (92.1%) 46 (35.9%) 59 (46.1%) 23 (18.0%) 23.7 ⫾ 5.8 3.2 ⫾ 0.4 1.6 ⫾ 1.0
0.705 0.821 0.405 0.228 0.194 0.002 0.083 0.743 0.676 0.492 0.617 0.924 0.776 0.207 0.065 0.686
ACC/AHA ⫽ American College of Cardiology/American Heart Association; TIMI ⫽ Thrombolysis In Myocardial Infarction.
ing treatment practice and outcomes. The registry includes 50 community and teaching hospitals that enroll ⬎10,000 patients annually. As of August 2007, the registry contained data for 12,634 patients. The KAMIR is
supported by a research grant from the Korean Circulation Society in commemoration of its 50th anniversary and aims to improve patient care by providing greater understanding of patient management and outcomes in
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Table 3 In-hospital events and clinical outcomes at 30 days, 6 months, and 12 months Variable
Time From Thrombolysis to PCI (h)
In-hospital Death Severe bleeding 30 d after discharge Death Myocardial infarction Repeated PCI Target-vessel revascularization Coronary artery bypass grafting Total MACEs 6 mo Death Myocardial infarction Repeated PCI Target-vessel revascularization Coronary artery bypass grafting Total MACEs 12 mo Death Myocardial infarction Repeated PCI Target-vessel revascularization Coronary artery bypass grafting Total MACEs
⬍24
24–48
48–72
ⱖ72
n ⫽ 81 0 (0%) 0 (0%) n ⫽ 70 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) n ⫽ 52 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) n ⫽ 38 1 (2.6%) 0 (0%) 1 (2.6%) 1 (2.6%) 0 (0%) 2 (5.3%)
n ⫽ 79 1 (1.3%) 0 (0%) n ⫽ 67 1 (1.5%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (1.5%) n ⫽ 51 1 (2.0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (2.0%) n ⫽ 36 1 (2.8%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (2.8%)
n ⫽ 79 1 (1.3%) 1 (1.3%) n ⫽ 67 1 (1.5%) 0 (0%) 2 (2.9%) 1 (1.5%) 0 (0%) 3 (4.4%) n ⫽ 47 1 (2.1%) 0 (0%) 6 (12.8%) 5 (10.6%) 0 (0%) 7 (14.9%) n ⫽ 38 3 (7.9%) 0 (0%) 6 (15.8%) 5 (13.2%) 0 (0%) 9 (23.7%)
n ⫽ 144 0 (0%) 0 (0%) n ⫽ 124 1 (0.8%) 0 (0%) 1 (0.8%) 1 (0.8%) 0 (0%) 2 (1.6%) n ⫽ 100 3 (3.0%) 0 (0%) 4 (4.0%) 1 (1.0%) 0 (0%) 7 (7.0%) n ⫽ 76 3 (3.9%) 0 (0%) 5 (6.6%) 2 (2.6%) 0 (0%) 8 (10.5%)
Table 4 Clinical outcomes of percutaneous coronary intervention (PCI) before and after 24 hours of thrombolytic therapy
6-mo outcomes Death Repeated PCI Target-vessel revascularization Total MACEs 12-mo outcomes Death Repeated PCI Target-vessel revascularization Total MACEs
p Value
⬍24 h
ⱖ24 h
n ⫽ 52 0 (0%) 0 (0%) 0 (0%) 0 (0%) n ⫽ 38 1 (2.6%) 1 (2.6%) 1 (2.6%) 2 (5.3%)
n ⫽ 198 5 (2.5%) 10 (5.1%) 6 (3.0%) 15 (7.6%) n ⫽ 150 7 (4.7%) 11 (7.3%) 7 (4.7%) 18 (12.0%)
0.684 0.278 0.530 0.257
the rapidly evolving field of acute myocardial infarction (AMI) treatment. The diagnosis of STEMI was based on a suggestive history with ST elevation ⬎2 mm in ⱖ2 precordial leads, ST elevation ⬎1 mm in ⱖ2 limb leads, or new left branch bundle block on the 12-lead electrocardiogram with a concomitant increase in troponin-I or -T ⱖ99th percentile of the upper reference limit. Patients aged 18 to 80 years were considered eligible for thrombolytic therapy up to 12 hours from the onset of symptoms. Contraindications to thrombolytic therapy included cardiogenic shock, defined as sustained systolic blood pressure ⬍90 mm Hg with no response to fluids or systolic blood pressure ⬍100 mm Hg with vasopressor use; severe hypertension (⬎180/110 mm Hg); previous stroke; recent major surgery or trauma; prolonged cardiopulmonary resuscitation; active bleeding; oral anticoagulation with warfarin; or hemorrhagic diathesis. Varying
0.730 0.239 0.228 0.217 0.647 0.004 0.005 0.009 0.542 0.014 0.043 0.015
Table 5 Clinical outcomes of percutaneous coronary intervention (PCI) before and after 48 hours of thrombolytic therapy
p Value 0.246 0.169 0.281 0.075
0.413 0.277
6-mo outcomes Death Repeated PCI Target-vessel revascularization Total MACEs 12-mo outcomes Death Repeated PCI Target-vessel revascularization Total MACEs
⬍48 h
ⱖ48 h
n ⫽ 103 1 (1.0%) 0 (0%) 0 (0%) 1 (1.0%) n ⫽ 74 2 (2.7%) 1 (1.4%) 1 (1.4%) 3 (4.1%)
n ⫽ 147 4 (2.7%) 10 (6.8%) 6 (4.1%) 14 (9.5%) n ⫽ 114 6 (5.3%) 11 (9.6%) 7 (6.1%) 17 (14.9%)
p Value 0.344 0.028 0.031 0.014 0.384 0.034 0.039 0.026
thrombolytic regimens (urokinase, accelerated alteplase, and tenecteplase) were used during the study period. Patients underwent elective PCI within 2 weeks of successful thrombolysis after receiving loading doses of oral aspirin (300 mg) and clopidogrel (600 mg). The culprit artery underwent stent placement if the stenosis was morphologically suitable and the procedure was expected to achieve an adequate result. Nonculprit lesions underwent stent placement only if a large amount of myocardium was threatened by severe stenosis. Although administration of glycoprotein IIb/IIIa inhibitor depended on the discretion of the operator, it was usually used in interventional patients with clear angiographic evidence of thrombus. Patients who had a clear indication for urgent PCI, such as shock, persistent or recurrent chest pain, or ST-segment elevation, were excluded from the analysis. Patients who underwent a revascularization procedure as a result of failed
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Table 6 Clinical outcomes of percutaneous coronary intervention (PCI) before and after 72 hours of thrombolytic therapy
6-mo outcomes Death Repeated PCI Target-vessel revascularization Total MACEs 12-mo outcomes Death Repeated PCI Target-vessel revascularization Total MACEs
⬍72 h
ⱖ72 h
n ⫽ 142 2 (1.3) 6 (4.0) 5 (3.3) 8 (5.3) n ⫽ 112 5 (4.5) 7 (6.3) 6 (5.4) 12 (10.7)
n ⫽ 93 3 (3.0) 4 (4.0) 1 (1.0) 7 (7.0) n ⫽ 76 3 (3.9) 5 (6.6) 2 (2.6) 8 (10.5)
p Value 0.529 0.995 0.255 0.729 0.813 0.855 0.427 0.994 Figure 1. Twelve-month MACE-free survival according to PCI before and after 24 hours of thrombolytic therapy.
thrombolysis, early reinfarction, or ischemia after the initial thrombolytic therapy were also excluded. Major adverse cardiac events (MACEs) included death, myocardial infarction, and need for repeated target-vessel revascularization. Target-vessel revascularization was defined as any repeated intervention driven by lesions located in the treated vessel within and beyond the target lesion limits. Smoking was defined as any history of tobacco smoking. Hypertension was defined as a history of hypertension or antihypertensive medication use, and diabetes was defined as a history of diabetes and use of insulin or oral hypoglycemic agents on entry into the study. Hyperlipidemia was defined as a diagnosis previously made by a physician or treatment with lipid-lowering medications. Major bleeding or vascular complication was defined as any complication causing death, need for surgery or transfusion, or extended time in the hospital. Study end points were in-hospital complications, including death, myocardial infarction, bleeding complications, and the composite end point of MACEs, including death, myocardial infarction, and urgent revascularization. Clinical follow-up with respect to MACEs occurred at 30 days, 6 months, and 12 months after the baseline procedure. All statistical analyses were performed using SPSS, version 15.0 (SPSS Inc., Chicago, Illinois) for Windows (Microsoft Corp., Redmond, Washington). Continuous variables were presented as mean ⫾ SD and compared using Student’s t test (when group distributions were symmetrical and mounded) or Mann-Whitney U test (when group distributions were skewed). Chi-square test (when all expected cell counts were ⱖ5) or Fisher’s exact test (when any expected cell count was ⬍5) was used to determine the significance of differences in categorical variables. Comparisons of MACE rates among groups were adjusted on baseline variables (Table 1) using Cox proportional hazards models. All statistical tests were 2 tailed, and a p value ⬍0.05 was considered statistically significant. Results There were no differences among the 4 groups in baseline clinical characteristics (Table 1). For type of thrombolytic agent used, group 1 used mostly tenecteplase compared with group 4, which was evenly balanced. Analysis of angiographic findings showed no differences in location of
Figure 2. Twelve-month repeated PCI–free survival according to PCI before and after 24 hours of thrombolytic therapy.
Figure 3. Twelve-month MACE-free survival according to PCI before and after 48 hours of thrombolytic therapy.
culprit lesions, American College of Cardiology/American Heart Association lesion score, or prevalence of multivessel disease (Table 2). The rate of pre-PCI Thrombolysis In Myocardial Infarction grade 3 significantly increased as the interval between thrombolysis and PCI increased (p ⫽ 0.002). However, the post-PCI Thrombolysis In Myocardial Infarction grade 3 rate was not different among groups. There were no differences in the incidences of major bleeding, in-hospital mortality, and 30-day outcomes among
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tively, p ⫽ 0.014; Table 3). When patients were dichotomized according to time of PCI, such as within and after 24, 48, and 72 hours of thrombolysis, significant differences in MACEs and repeated PCI were found only between patients who underwent PCI ⬍48 hours after thrombolytic therapy and those who underwent PCI ⱖ48 hours after thrombolysis (Tables 4-6; Figures 1-6). Rates of composite MACEs and repeated PCI at 6 and 12 months were significantly lower in patients who underwent PCI within 48 hours of thrombolytic therapy compared with those who underwent PCI later (6-month MACEs: 1.0% vs 9.5%, p ⫽ 0.014; 6-month repeated PCI: 0% vs 6.8%, p ⫽ 0.028; 12-month MACEs: 4.1% vs 14.9%, p ⫽ 0.026; 12-month repeated PCI: 1.4% vs 9.6%, p ⫽ 0.034; Table 5; Figures 3 and 4). Figure 4. Twelve-month repeated PCI–free survival according to PCI before and after 48 hours of thrombolytic therapy.
Figure 5. Twelve-month MACE-free survival according to PCI before and after 72 hours of thrombolytic therapy.
Figure 6. Twelve-month repeated PCI–free survival according to PCI before and after 72 hours of thrombolytic therapy.
groups (Table 3). However, at 6 months, there were significant interactions in rates of composite MACEs and repeated PCI among groups (MACEs: 0%, 2.0%, 14.9%, and 7.0%, respectively, p ⫽ 0.009; repeated PCI: 0%, 0%, 12.8%, and 4.0%, respectively, p ⫽ 0.004; Table 3). Likewise, there were significant differences among groups in rates of composite MACEs and repeated PCI at 12 months (MACEs: 5.3%, 2.8%, 23.7%, and 10.5%, respectively, p ⫽ 0.015; repeated PCI: 2.6%, 0%, 15.8%, and 6.6%, respec-
Discussion Our results suggested that early elective PCI after successful thrombolytic therapy was safe and effective in patients with acute STEMI, especially when performed within 48 hours of thrombolysis. Early routine PCI (ⱖ24 hours) after thrombolytic therapy, rather than the traditional conservative approach of delayed and/or ischemia-guided PCI, is a controversial issue. Randomized trials during the “balloon era” found no benefit of a routine invasive strategy on clinical outcomes.1– 4 This strategy was progressively discouraged because of unsatisfactory results and unacceptable bleeding. However, recently there has been convincing evidence from several studies that PCI after successful thrombolysis for STEMI is better than no PCI or ischemia-driven PCI.5–12 These results highlight not only the effectiveness of stent placement in patients with STEMI, but also the beneficial impact of adjunctive pharmacotherapy because stent placement has not consistently been shown to reduce mortality in the setting of AMI. Although glycoprotein IIb/IIIa receptor inhibitors in combination with stent placement may be of benefit to patients with AMI, their use was highly variable and overall low in the studies of thrombolytic therapy.13–15 The combination of full-dose thrombolysis with pharmacotherapy associated with immediate PCI (1 to 3 hours) may increase the risk of bleeding, as shown in the recently halted ASsessment of the Safety and Efficacy of a New Treatment strategy with Percutaneous Coronary Intervention (ASSENT-4) trial,16 whereas routine but deferred PCI, 17 hours after thrombolysis in the Grupo de Analisis de la Cardiopatia Isquemica Aguda (GRACIA) trial, 24 hours in the Which Early ST-elevation myocardial infarction Therapy (WEST) Study, and 3 to 12 hours in GRACIA-2, was safer and reduced major bleeding complications.9,11,17 Recently, Agati et al18 also reported that early PCI (20 hours) after thrombolysis was more effective in preserving myocardial perfusion and function than thrombolysis alone. All these results show that routine but deferred PCI may be more beneficial in reducing infarct size and long-term mortality than immediate PCI.19 In the present multicenter registry experience, early elective PCI within 48 hours of thrombolytic therapy for patients with acute STEMI appeared safe and more effective compared with PCI deferred ⬎48 hours. The major benefit of the early invasive approach was a significant reduction in the need for repeated PCI. Although not fully explainable,
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the benefit of early routine PCI may be through its favorable effect in preventing additional coronary events associated with both infarcted and noninfarcted viable myocardium jeopardized by remaining ischemia, as well as in recovering and maintaining the permeability of the infarct-related artery. Regarding the optimal time for routine elective PCI, our analysis suggested that PCI be performed within 48 hours of successful thrombolytic therapy, although this warrants further validation through large randomized prospective trials. The present study was limited because of its retrospective nature and was therefore subject to the limitations pertinent to this type of clinical investigation. Patients presenting in cardiogenic shock and with in-hospital unstable clinical conditions were excluded from this study. Elderly patients (⬎80 years) were also excluded to reduce the risk of bleeding complications. It lacked systematic angiographic follow-up and quantitative coronary analysis that might affect the rate of target-vessel revascularization. Differences between the institutions involved in this research, although representative of the reality of the country’s health system, may to some extent have introduced unintentional bias. Type of thrombolytic agent used was not evenly balanced among groups. However, on multivariate analysis, this difference did not affect clinical outcomes. Regarding major bleeding, our study was not large enough to provide reliable estimates of the relative safety. Since the sample size was relatively small, results of the present study cannot necessarily be generalized to the treatment of patients with STEMI in general practice. Future large prospective studies are warranted. Acknowledgment: KAMIR Investigators: Myung Ho Jeong, MD, Young Keun Ahn, MD, Shung Chull Chae, MD, Jong Hyun Kim, MD, Seung Ho Hur, MD, Young Jo Kim, MD, In Whan Seong, MD, Dong Hoon Choi, MD, Jei Keon Chae, MD, Taek Jong Hong, MD, Jae Young Rhew, MD, Doo Il Kim, MD, In Ho Chae, MD, Jung Han Yoon, MD, Bon Kwon Koo, MD, Byung Ok Kim, MD, Myoung Yong Lee, MD, Kee Sik Kim, MD, Jin Yong Hwang, MD, Myeong Chan Cho, MD, Seok Kyu Oh, MD, Nae Hee Lee, MD, Kyoung Tae Jeong, MD, Seung Jea Tahk, MD, Jang Ho Bae, MD, Seung Woon Rha, MD, Keum Soo Park, MD, Chong Jin Kim, MD, Kyoo Rok Han, MD, Tae Hoon Ahn, MD, Moo Hyun Kim, MD, Ki Bae Seung, MD, Wook Sung Chung, MD, Ju Young Yang, MD, Chong Yun Rhim, MD, Hyeon Cheol Gwon, MD, Seong Wook Park, MD, Young Youp Koh, MD, Seung Jae Joo, MD, Soo Joong Kim, MD, Dong Kyu Jin, MD, Jin Man Cho, MD, Yang Soo Jang, MD, Jeong Gwan Cho, MD, and Seung Jung Park, MD. 1. Topol EJ, O’Neill WW, Langburd AB, Walton JA Jr., Bourdillon PD, Bates ER, Grines CL, Schork AM, Kline E, Pitt B. A randomized, placebo-controlled trial of intravenous recombinant tissue-type plasminogen activator and emergency coronary angioplasty in patients with acute myocardial infarction. Circulation 1987;75:420 – 428. 2. Belenkie I, Knudtson ML, Roth DL, Hansen JL, Traboulsi M, Hall CA, Manyari D, Filipchuck NG, Schnurr LP, Rosenal TW. Relation between flow grade after thrombolytic therapy and the effect of angioplasty on left ventricular function: a prospective randomized trial. Am Heart J 1991;121:407– 416. 3. The TIMI Research Group. Immediate versus delayed catheterization and angioplasty following thrombolytic therapy for acute myocardial infarction: TIMI II-A results. JAMA 1988;260:2849 –2858.
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