INTRODUCTION MATERIALS AND METHODS

Transcription

1 J Korean Med Sci 2008; 23: ISSN DOI: /jkms Coyright The Korean Academy of Medical Sciences The Imact of Initial Treatment Delay Using Primary Angiolasty on Mortality among Patients with Acute Myocardial Infarction: from the Korea Acute Myocardial Infarction Registry The imact of treatment delays to reerfusion on atient mortality after rimary ercutaneous coronary intervention (PCI) for ST elevation myocardial infarction (STEMI) is controversial. We analyzed 5,069 atients included in the Korea Acute Myocardial Infarction Registry (KAMIR) between November 2005 and January We selected,46 atients who resented within 2 hr of symtom onset and who were treated with rimary PCI. The overall mortality at one month was 4.4%. The medians of door-to-balloon time, symtom onset-to-balloon time, and symtom onset-to-door time were 90 (interquartile range, 65-36), 274 (85-442), and 63 min (90-285), resectively. One-month mortality was not increased significantly with any increasing delay in door-to-balloon time (4.3% for 90 min, 4.4% for >90 min; =0.94), symtom onset-to-balloon time (3.9% for 240 min, 4.8% for >240 min; =0.4), and symtom onset-to-door time (3.3% for 20 min, 5.0% for >20 min; =0.3). These time variables had no imact on one-month mortality in any subgrou. Thus, this first nationwide registry data in Korea showed a good result of rimary PCI, and the atient rognosis may not deend on the initial treatment delay using the current rotocols. Key Words : Myocardial Infarction; Mortality; Angiolasty Young Bin Song, Joo-Yong Hahn, Hyeon-Cheol Gwon, Jun Hyung Kim, Sang Hoon Lee, Myung-Ho Jeong*, and KAMIR investigators Deartment of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul; Heart Center of Chonnam National University Hosital*, Chonnam National University Research Institute of Medical Sciences, Gwangju, Korea The first two authors contributed equally to this work. Received : 5 March 2007 Acceted : 20 Setember 2007 Address for corresondence Hyeon-Cheol Gwon, M.D. Cardiac and Vascular Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 35-70, Korea Tel : , Fax : hcgwon@smc.samsung.co.kr INTRODUCTION A shorter time to reerfusion is beneficial in treating atients with fibrinolytic theray for acute ST-segment elevation myocardial infarction (STEMI) (-4). In contrast, there is some controversy regarding the relationshi between mortality and time to reerfusion with rimary ercutaneous coronary intervention (PCI), although the American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend that the door-to-balloon time (or medical contact-to-balloon) for PCI should be ket under 90 min (5). Some studies have shown that delays in symtom onset-to-balloon time (6-9) or door-to-balloon time adversely affects the rognosis in atients with STEMI (0, ). However, in other studies, there was no significant difference in clinical outcomes according to the time to reerfusion (4, 2). In addition, because the initial treatment delay is an imortant quality indicator of the treatment for such atients, it is worthwhile to investigate how many cases are erformed according to the guidelines. Therefore, the aim of this study was to evaluate the current status of delay in the time to reerfusion during rimary PCI and its imact on atient mortality one month later using data from the Korea Acute Myocardial Infarction Registry (KAMIR), the first nationwide multicenter registry of acute MI in Korea. We also tried to define the subgrous that were mostly influenced by treatment delay. MATERIALS AND METHODS Study design and subjects A cohort of atients with STEMI who underwent rimary PCI was selected from the KAMIR, which is a nationwide study for acute myocardial infarction in Korea. Between November 2005 and January 2007, 5,069 atients at 4 hositals were registered. Patients were eligible for enrollment if they had STEMI, resented within 2 hr after symtom onset, and were treated with rimary PCI, and if they had comleted a 30-day clinical follow-u at the analysis time oint. The following atients were excluded sequentially: atients without ST elevation or left bundle branch block on the first electrocardiogram (n=2,076), those with cardiogenic shock (n=37), those with unknown time of symtom onset or missing data 357

2 358 Y.B. Song, J.-Y. Hahn, H.-C. Gwon, et al. Without ST-elevation of LBBB on ECG N=2,076 Time to resentation 2 hr N=42 Conservative treatment N=93 KAMIR N=5,069 AMI atients 4 Hositals,993 Reerfusion eligible STEMI atients Reerfusion theray with rimary PCI N=,530 Study Poulation,46 atients 4 Hositals Cardiogenic shock N=37 With unknown time of symtom onset or missing data N=442 Reerfusion theray with thrombolysis N=270 -month follow-u loss N=4 Fig.. Selection criteria. (n=442), and those with symtom onset-to-door time 2 hr (n=42). Among the 5,069 atients,,993 atients had reerfusion eligible for STEMI and,800 (90.3%) received reerfusion theray. Reerfusion theray with rimary PCI was erformed in,530 atients (85.0% of,800) and with thrombolysis in 270 (5.0% of,800). Patients who did not undergo the one-month follow-u were excluded (n=4). We finally included,46 atients with STEMI who were treated with rimary PCI and who comleted the one-month follow-u (Fig. ). Demograhic and clinical characteristics recorded were gender, age, and medical history. The latter included any history of smoking, dysliidemia, hyertension, diabetes mellitus, chronic renal insufficiency, stroke, ischemic heart disease, family history of coronary artery disease, revious PCI, revious coronary artery byass graft surgery, or any ast regular medication. The resentation characteristics included symtoms at admission, systolic and diastolic blood ressure, heart rate and rhythm, Killi classification, the results of the diagnostic electrocardiograhy (ECG), and ischemic location on ECG. Definitions and outcomes measures Time variables were defined as follows: door-to-balloon time was the time from arrival in the emergency deartment until initial balloon inflation; symtom onset-to-balloon time was the time from the onset of symtoms until the first balloon inflation; and symtom onset-to-door time was the time from the onset of symtoms until arrival in the emergency deartment. Patients were divided into two grous according to door-to-balloon time ( 90 min and >90 min), symtom onset-to-balloon time ( 240 min and >240 min), and symtom onset-to-door time ( 20 min and >20 min), resectively. The main outcomes were mortality at one month and major cardiovascular adverse events (MACEs). MACEs included death, reinfarction, and target vessel revascularization. Statistical analysis SPSS for Windows (version 2.0; SPSS Inc., Chicago, IL, U.S.A.) was used for all analyses. Continuous data are exressed as the mean±sd or as the median and interquartile range (25th and 75th ercentiles); categorical data were exressed as ercentages. Statistical comarisons of baseline, angiograhic, and outcome variables were erformed for categorical variables using the Chi-squared test or Fisher s exact test (if the exected value of the variable was <5 in at least one grou). Student s t test was alied to continuous variables. <0.05 was considered statistically significant. Multile logistic regression analysis was erformed to assess the relation between redictor variables and one-month mortality. Baseline characteristics RESULTS Medians of times to treatment were as follows: door-toballoon time, 90 min (interquartile range, min); symtom onset-to-balloon time, 274 min (85-442); and symtom onset-to-door time, 63 min (90-285). Of all atients, 36% resented to the hosital within 20 min of symtom onset. Door-to-balloon time was 90 min or less in 5% of atients and 42% of atients were reerfused within 240 min of symtom onset. A ost-pci thrombolysis in myocardial infarction (TIMI) grade 3 flow was achieved in 92.8% of the atients. Demograhic, clinical, and angiograhic characteristics according to door-to-balloon time, symtom onset-to-balloon time, and symtom onset-to-door time are resented in Table. Patients with door-to-balloon times >90 min had hyertension and Killi class 3 more frequently than did

3 Treatment Delay in Primary Angiolasty 359 Table. Baseline atient characteristics by time variables Door-to-balloon time 90 (n=75) >90 (n=70) Symtom onset-to-balloon time 240 (n=597) >240 (n=89) Symtom onset-to-door time 20 (n=55) >20 (n=90) Clinical variables Age (yr) 60.8± ± ± ±2.8 < ± ±2.6 <0.0 Age >70 yr < <0.0 Women < <0.0 Diabetes mellitus Hyertension < < Prior MI Prior PCI Anterior infarction Killi class < Serum Cr.5 mg/dl Angiograhic/rocedural variables Pre-PCI TIMI 0- flow Post-PCI TIMI 3 flow Multivessel diseases Ejection fraction 5.5± ± ± ±.8 < ±. 50.4±.9 <0.0 MI, myocardial infarction; PCI, ercutaneous coronary intervention; Cr, creatinine; TIMI, thrombolysis in myocardial infarction. Table 2. One-month outcomes by time variables Door-to-balloon time (min) 90 (n=75) >90 (n=70) Symtom onset-to-balloon time (min) 240 >240 (n=597) (n=89) Symtom onset-to-door time (min) 20 (n=55) >20 (n=90) Mortality MACEs Follow-u LVEF 54.3± ± ± ± ± ± MACEs, major adverse cardiovascular events; LVEF, left ventricular ejection fraction. Survival = min >90 min Days from MI onset longer symtom onset-to-balloon times than in those with shorter symtom onset-to-balloon times. Patients with longer symtom onset-to-door times tended to be older, to be women, and to have anterior infarction more frequently and lower left ventricular ejection fraction than did atients with shorter symtom onset-to-door times. Of the atients enrolled in the study, 262 atients (8.5%) were treated with glycorotein IIb/IIIa inhibitors. Trile antilatelet agents with asirin, cloidogrel, and cilostazol were rescribed in 598 atients (42.%). One-hundred and twenty-two atients (8.6%) with antilatelet use before the index MI were not statistically different in mortality (5.7% vs. 4.3%, =0.44) and MACE (7.4% vs. 5.5%, =0.39) comared with those without antilatelet use. Sixty-three atients (4.5%) were treated with statin before the index MI. Fig. 2. Kalan-meier estimates of cumulative survival stratified by door-to-balloon time. atients with door-to-balloon times 90 min. The revalences of older atients, women, having diabetes mellitus, hyertension, Killi class 3, multivessel disease, and lower left ventricular ejection fraction were higher in atients with Clinical outcomes by time variables Sixty-two atients (4.4%) had died by one month after the rocedure. Table 2 shows the association between treatment delay and clinical outcomes. Mortality at this oint did not increase significantly with increasing delay in door-

4 360 Y.B. Song, J.-Y. Hahn, H.-C. Gwon, et al. -month mortality =0.47.2% 4.3% 4.4% 5.0% -month MACE = % 4.7% 7.0% 6.% >6 Symtom onset-to-balloon time (hr) A >6 Symtom onset-to-balloon time (hr) B Fig. 3. The one-month mortality (A) and MACEs (B) stratified by door-to-balloon time. -month mortality % 5.7% 5.% 2.3% =0.37 -month MACE % 6.8% 6.6% 4.% = >80 Door-to-balloon time (min) A >80 Door-to-balloon time (min) B Fig. 4. The one-month mortality (A) and MACEs (B) stratified by symtom onset-to-balloon time. Table 3. Univariate redictors of one-month mortality and MACEs Mortality (n=62) MACEs (n=80) Clinical variables Age >70 yr 37/43 (8.6%) <0.0 4/43 (9.5%) <0.0 Women 27/354 (7.6%) <0.0 28/354 (7.9%) 0.03 Diabetes mellitus 6/33 (4.8%) /33 (6.3%) 0.49 Hyertension 30/637 (4.7%) /637 (6.%) 0.42 Prior myocardial infarction 3/39 (7.7%) 0.3 6/39 (5.4%) <0.0 Prior PCI 2/48 (4.2%) /48 (8.3%) 0.4 Anterior infarction 35/750 (4.7%) /750 (6.%) 0.44 Killi classification 3 20/5 (7.4%) <0.0 2/5 (8.3%) <0.0 Serum creatinine.5 mg/dl 4/0 (3.9%) <0.0 7/0 (6.8%) <0.0 Ejection fraction 40% 25/232 (0.8%) <0.0 29/232 (2.5%) <0.0 Angiograhic/rocedural variables Pre-PCI TIMI 0- flow 48/994 (4.8%) /994 (5.8%) 0.43 Post-PCI TIMI 0-2 flow 5/00 (5.0%) <0.0 6/00 (6.0%) <0.0 Multivessel diseases 46/702 (6.6%) <0.0 63/702 (9.0%) <0.0 MACEs, major adverse cardiovascular events; PCI, ercutaneous coronary intervention; TIMI, thrombolysis in myocardial infarction. to-balloon time (4.3% for 90 min vs. 4.4% for >90 min; =0.94), symtom onset-to-balloon time (3.9% for 240 min vs. 4.8% for >240 min; =0.4), and symtom onsetto-door time (3.3% for 20 min vs. 5.0% for >20 min; =0.3) (Fig. 2). The rate of MACEs at one month was not significantly different according to door-to-balloon time, symtom onset-to-balloon time, or symtom onset-to-door time. When atients were divided into 4 grous according to door-to-balloon time ( 90, 90-20, 20-80, 80 min) or symtom onset-to-balloon time ( 2, 2-4, 4-6, 6 hr), incremental delays in reerfusion aeared to have little effect on the one-month mortality and MACE rate (Fig. 3, 4). The left ventricular ejection fraction at the one-month follow-u was also similar between the early reerfused and late reer-

5 Treatment Delay in Primary Angiolasty 36 Table 4. Multivariate redictors of one-month mortality and MACEs Odds ratio of mortality (95% confidence interval) Odds ratio of MACEs (95% confidence interval) Age >70 yr 2.43 ( ) ( ) 0.44 Women.34 ( ) ( ) 0.66 Serum creatinine ( ) < ( ) 0.0 Killi classification ( ) < ( ) 0.0 LVEF 40% 8.02 ( ) < ( ) <0.0 Multivessel disease 2.6 ( ) ( ) <0.0 Post-PCI TIMI flow ( ) ( ) 0.06 MACEs, major adverse cardiovascular events; LVEF, left ventricular ejection fraction; PCI, ercutaneous coronary intervention; TIMI, thrombolysis in myocardial infarction. Table 5. One-month mortality by time variables in atients subsets Door-to-balloon time 90 min >90 min Symtom onset-to-balloon time 240 min >240 min Symtom onset-to-door time 20 min >20 min Age >70 yr (n=43) 24/209 (.5) 3/222 (5.9) /40 (8.6) 25/29 (8.6) 0.99 /09 (0.) 26/322 (8.) 0.52 Age 70 yr (n=985) 7/506 (.4) 8/479 (3.8) 0.06 /457 (2.4) 4/528 (2.7) 0.8 6/406 (.5) 9/579 (3.3) 0.08 Serum Cr.5 mg/dl (n=0) 9/43 (20.9) 5/58 (8.6) /36 (3.9) 9/65 (3.8) /37 (5.4) 2/64 (8.8) 0.06 Serum Cr <.5 mg/dl (n=,306) 2/668 (3.) 26/638 (4.) /557 (3.2) 29/749 (3.9) /473 (3.2) 32/833 (3.8) 0.53 Killi class 3-4 (n=5) 5/39 (2.8) 5/76 (9.7) /38 (5.8) 4/77 (8.2) /43 (4.0) 4/72 (9.4) 0.45 Killi class -2 (n=,28) 26/666 (3.9) 6/65 (2.6) 0.9 7/549 (3.) 25/732 (3.4) 0.75 /463 (2.4) 3/88 (3.8) 0.7 LVEF 40% (n=232) 2/06 (.3) 3/26 (0.3) 0.8 9/72 (2.5) 6/60 (0.0) /65 (0.8) 8/67 (0.8) 0.99 LVEF >40% (n=,045) 6/543 (.) 4/502 (0.8) 0.6 0/454 (0) 0/59 (.7) /392 (0) 0/653 (.5) 0.06 Post-PCI TIMI <3 (n=00) 5/47 (0.6) 0/53 (8.9) /35 (7.) 9/65 (3.8) /33 (5.2) 0/67 (4.9) 0.98 Post-PCI TIMI 3 (n=,286) 26/657 (4.0) 8/629 (2.9) /549 (2.7) 29/737 (3.9) /472 (2.) 34/84 (4.2) 0.06 High risk* (n=682) 29/38 (9.) 23/364 (6.3) 0.7 9/228 (8.3) 33/454 (7.3) /99 (7.0) 38/483 (7.9) 0.7 Low risk (n=734) 2/397 (0.5) 8/337 (2.4) /369 (.) 6/365 (.6) 0.5 3/36 (0.9) 7/48 (.7) 0.40 *High risk: Age >70 yr; serum creatinine.5 mg/dl; Killi class 3; LVEF 40% or ost-pci TIMI <grade 3. Cr, creatinine; LVEF, left ventricular ejection fraction; PCI, ercutaneous coronary intervention; TIMI, thrombolysis in myocardial infarction. fused atients regarding door-to-balloon time, symtom onset-to-balloon time, and symtom onset-to-door time. Predictors of one-month clinical outcomes Alying univariate analysis, various clinical and angiograhic or rocedural variables were significantly associated with one-month mortality and MACEs (Table 3). In multivariate analysis, old age (>70 yr), Killi class 3, serum creatinine.5 mg/dl, ost-pci TIMI flow grades of 0-2, and left ventricular dysfunction (ejection fraction 40%) were significantly associated with mortality. From the multivariate analysis, Killi class 3, serum creatinine.5 mg/ dl, left ventricular dysfunction (ejection fraction 40%), and multivessel disease were indeendent redictors for MACEs (Table 4). Clinical outcomes by time variables in subgrous We erformed subgrou analysis to identify those atients with outcomes most influenced by treatment delay. Based uon multivariate analysis for one-month mortality, we divided atients by age, serum creatinine, Killi classification, left ventricular ejection fraction, and ost-pci TIMI flow grade. Treatment delay was not significantly associated with increased short-term mortality in any subgrou. Moreover, among atients at high risk (age >70 yr, serum creatinine.5 mg/dl, Killi classification 3, left ventricular ejection fraction 40%, ost-pci TIMI flow grades 0-2), the increase in door-to-balloon time, symtom onset-to-balloon time, or symtom onset-to-door time did not correlate with one-month mortality; nor were there any such associations among low-risk atients (Table 5). DISCUSSION Primary PCI was the referred reerfusion strategy in this registry, and more than half of the atients underwent rimary PCI within the time window recommended in the guidelines. The one-month mortality was 4.4% and was not increased significantly with increasing delay in door-toballoon time, symtom onset-to-balloon time, or symtom onset-to-door time. These time variables had no imact on

6 362 Y.B. Song, J.-Y. Hahn, H.-C. Gwon, et al. one-month mortality in any subgrou. Among 5,069 atients registered in the KAMIR between November 2005 and January 2007,,993 atients had STEMI and was eligible for reerfusion. Reerfusion theray was erformed over 90% of these atients, and only a minority received conservative treatment. The rate of receiving reerfusion theray among these eligible atients with STEMI in the KAMIR seems to be higher than in revious data. From data of the National Registry of Myocardial Infarction (NRMI) in the U.S.A., one-half of the atients with STEMI who were eligible for reerfusion received reerfusion theray (3). Notably, rimary PCI was the overwhelmingly referred reerfusion strategy in this registry. Among those atients receiving reerfusion theray, rimary PCI was erformed in 85%. This rate of rimary PCI is much higher than results from other countries, which showed that rimary PCI was erformed in one-fourth to one-third (3, 4). In the KAMIR, the incidence of ost-pci TIMI grade 3 flow was also very high at 92.8%. This is higher than that reorted in studies from the U.S.A. (5, 6). Moreover, the median door-to-balloon time was 90 min, which means that one-half of atients undergoing rimary PCI received reerfusion in the recommended time in this registry. Recently ublished studies in U.S.A. showed that fewer than one-half of atients with STEMI received reerfusion in the recommended door-to-balloon time, and the mean door-to-balloon time was 08.0 min (95% CI, min) (7). The growing interest in rimary PCI and easy accessibility to the large-volume hositals caable of erforming rimary PCI, most of which articiated in the KAMIR, may account for the higher erformance of rimary PCI in this registry than in those reorts. In our study, the overall one-month mortality was 4.4%. This rate is similar to that reorted in the NRMI in the U.S.A. (). Our study found that old age, high Killi class, left ventricular dysfunction, elevated serum creatinine, and ost-pci TIMI flow grades of 0-2 were indeendent redictors of one-month mortality after rimary PCI. These risk factors also redicted the mortality consistently with several other studies (8-20). Desite the notion the efficacy of fibrinolytic theray is largely deendent on time to reerfusion (-4, 2, 22), several studies suggest that time to reerfusion may be less imortant in PCI (0, ). Myocardial salvage has been found to be related to time from symtom onset to fibrinolytic theray but was not related to time from symtom onset to ballooning (2, 23). In some studies, delays in door-to-balloon time have an imact on late survival rates only in highrisk atients and in atients resenting early after the onset of symtoms (9). In our study, door-to-balloon time and symtom onset-to-balloon time also aeared to have little effect on one-month mortality and MACEs. Moreover, we could not identify any subgrous that were influenced by treatment delay. There are several ossible reasons for the oor relationshi between early mortality and time variables of treatment delay in rimary PCI, unlikely in fibrinolytic theray. First, with thrombolytic theray, the successful reerfusion rate decreases dramatically with delay to reerfusion (24, 25), whereas the rocedural success rate of rimary PCI remains high regardless of this (6, 2). Second, higher TIMI grade 3 flow was achieved even in the high-risk atients, regardless of time to reerfusion in atients with rimary PCI (6, 2). Third, death from myocardial ruture increases rogressively with increasing time to treatment with thrombolytic theray (26) but is uncommon following rimary PCI (27). Fourth, the assessment of the time of symtom onset is often difficult because of atient s reorting error. Patients frequently are unsure of the exact time of symtom onset and usually give an estimate. Finally, the atients with high risk factors are more rone to die before they arrive at hosital and are therefore selected out from this registry. It is likely that the exclusion of these atients decreased the effect of symtom onset-to-door time on mortality. Because time to reerfusion did not have a major imact on clinical outcomes in our study, in atients resenting to local hositals without interventional facilities, a transfer to interventional centers for rimary PCI may be considered desite additional treatment delays. Several randomized trials suggest that this imlication may be true (28-30). However, we would like to emhasize that these data do not defend treatment delay without a justifiable cause. We consider that all efforts should be made to shorten time to reerfusion following the ACC/AHA guidelines, which were based on six randomized controlled trials according to the Zwolle grou meta-analysis (5). Our study had several limitations. First, although the KAMIR is the nationwide multicenter trial in Korea, the number of atients, esecially in this study cohort, was relatively small. Therefore, the statistical ower to detect differences in mortality between time variable grous was limited. Second, we included only,46 atients from 5,069. Moreover, 4 atients (7.5%) of,530 who had been treated with rimary PCI did not undergo the one-month follow-u. This may influence the one-month mortality and MACE rate. Third, as mentioned reviously, only large hositals that were caable of erforming rimary PCI articiated in the KAMIR. Consequently, these subsets may not be reresentative of the entire cohort and this could have introduced selection bias. Finally, techniques of rimary PCI vary with hositals, which might have influenced the outcomes of rimary PCI, and in turn, the results of our study. In conclusion, this first nationwide registry of acute myocardial infarction in Korea showed a good result of rimary PCI. The one-month mortality was not associated with initial time variables to reerfusion, suggesting that atient rognosis may not deend on the initial treatment delay with the current ractice of rimary PCI. However, further stud-

7 Treatment Delay in Primary Angiolasty 363 ies are warranted to validate our observations. REFERENCES. Indications for fibrinolytic theray in susected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 000 atients. Fibrinolytic Theray Trialists (FTT) Collaborative Grou. Lancet 994; 343: Newby LK, Rutsch WR, Califf RM, Simoons ML, Aylward PE, Armstrong PW, Woodlief LH, Lee KL, Tool EJ, Van de Werf F. Time from symtom onset to treatment and outcomes after thrombolytic theray. GUSTO- Investigators. J Am Coll Cardiol 996; 27: Goldberg RJ, Mooradd M, Gurwitz JH, Rogers WJ, French WJ, Barron HV, Gore JM. Imact of time to treatment with tissue lasminogen activator on morbidity and mortality following acute myocardial infarction (The second National Registry of Myocardial Infarction). Am J Cardiol 998; 82: Zijlstra F, Patel A, Jones M, Grines CL, Ellis S, Garcia E, Grinfeld L, Gibbons RJ, Ribeiro EE, Ribichini F, Granger C, Akhras F, Weaver WD, Simes RJ. Clinical characteristics and outcome of atients with early (<2 h), intermediate (2-4 h) and late (>4 h) resentation treated by rimary coronary angiolasty or thrombolytic theray for acute myocardial infarction. Eur Heart J 2002; 23: Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, Hochman JS, Krumholz HM, Kushner FG, Lamas GA, Mullany CJ, Ornato JP, Pearle DL, Sloan MA, Smith SC Jr, Alert JS, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Gregoratos G, Halerin JL, Hiratzka LF, Hunt SA, Jacobs AK. ACC/AHA guidelines for the management of atients with ST-elevation myocardial infarction: a reort of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 999 Guidelines for the Management of Patients with Acute Myocardial Infarction). Circulation 2004; 0: e Brodie BR, Stuckey TD, Wall TC, Kissling G, Hansen CJ, Muncy DB, Weintraub RA, Kelly TA. Imortance of time to reerfusion for 30-day and late survival and recovery of left ventricular function after rimary angiolasty for acute myocardial infarction. J Am Coll Cardiol 998; 32: Antoniucci D, Valenti R, Migliorini A, Moschi G, Traani M, Buonamici P, Cerisano G, Bolognese L, Santoro GM. Relation of time to treatment and mortality in atients with acute myocardial infarction undergoing rimary coronary angiolasty. Am J Cardiol 2002; 89: De Luca G, Suryaranata H, Zijlstra F, van t Hof AW, Hoorntje JC, Gosselink AT, Dambrink JH, de Boer MJ. Symtom-onset-to-balloon time and mortality in atients with acute myocardial infarction treated by rimary angiolasty. J Am Coll Cardiol 2003; 42: Brodie BR, Stone GW, Cox DA, Stuckey TD, Turco M, Tcheng JE, Berger P, Mehran R, McLaughlin M, Costantini C, Lansky AJ, Grines CL. Imact of treatment delays on outcomes of rimary ercutaneous coronary intervention for acute myocardial infarction: analysis from the CADILLAC trial. Am Heart J 2006; 5: Berger PB, Ellis SG, Holmes DR Jr, Granger CB, Criger DA, Betriu A, Tool EJ, Califf RM. Relationshi between delay in erforming direct coronary angiolasty and early clinical outcome in atients with acute myocardial infarction: results from the global use of strategies to oen occluded arteries in Acute Coronary Syndromes (GUSTO-IIb) trial. Circulation 999; 00: Cannon CP, Gibson CM, Lambrew CT, Shoultz DA, Levy D, French WJ, Gore JM, Weaver WD, Rogers WJ, Tiefenbrunn AJ. Relationshi of symtom-onset-to-balloon time and door-to-balloon time with mortality in atients undergoing angiolasty for acute myocardial infarction. JAMA 2000; 283: Brodie BR, Stone GW, Morice MC, Cox DA, Garcia E, Mattos LA, Boura J, O Neill WW, Stuckey TD, Milks S, Lansky AJ, Grines CL. Imortance of time to reerfusion on outcomes with rimary coronary angiolasty for acute myocardial infarction (results from the Stent Primary Angiolasty in Myocardial Infarction Trial). Am J Cardiol 200; 88: Pinto DS, Kirtane AJ, Nallamothu BK, Murhy SA, Cohen DJ, Laham RJ, Cutli DE, Bates ER, Frederick PD, Miller DP, Carrozza JP, Jr, Antman EM, Cannon CP, Gibson CM. Hosital delays in reerfusion for ST-elevation myocardial infarction: imlications when selecting a reerfusion strategy. Circulation 2006; 4: Stenestrand U, Lindback J, Wallentin L. Long-term outcome of rimary ercutaneous coronary intervention vs rehosital and in-hosital thrombolysis for atients with ST-elevation myocardial infarction. JAMA 2006; 296: Bradley EH, Herrin J, Wang Y, McNamara RL, Radford MJ, Magid DJ, Canto JG, Blaney M, Krumholz HM. Door-to-drug and doorto-balloon times: where can we imrove? Time to reerfusion theray in atients with ST-segment elevation myocardial infarction (STEMI). Am Heart J 2006; 5: Nallamothu BK, Wang Y, Magid DJ, McNamara RL, Herrin J, Bradley EH, Bates ER, Pollack CV Jr, Krumholz HM. Relation between hosital secialization with rimary ercutaneous coronary intervention and clinical outcomes in ST-segment elevation myocardial infarction: National Registry of Myocardial Infarction- 4 analysis. Circulation 2006; 3: McNamara RL, Herrin J, Bradley EH, Portnay EL, Curtis JP, Wang Y, Magid DJ, Blaney M, Krumholz HM. Hosital imrovement in time to reerfusion in atients with acute myocardial infarction, 999 to J Am Coll Cardiol 2006; 47: De Luca G, Suryaranata H, Ottervanger JP, Antman EM. Time delay to treatment and mortality in rimary angiolasty for acute myocardial infarction: every minute of delay counts. Circulation 2004; 09: Brodie BR, Hansen C, Stuckey TD, Richter S, Versteeg DS, Guta N, Downey WE, Pulsiher M. Door-to-balloon time with rimary ercutaneous coronary intervention for acute myocardial infarction imacts late cardiac mortality in high-risk atients and atients resenting early after the onset of symtoms. J Am Coll Cardiol 2006; 47: McNamara RL, Wang Y, Herrin J, Curtis JP, Bradley EH, Magid DJ, Peterson ED, Blaney M, Frederick PD, Krumholz HM. Effect of

8 364 Y.B. Song, J.-Y. Hahn, H.-C. Gwon, et al. door-to-balloon time on mortality in atients with ST-segment elevation myocardial infarction. J Am Coll Cardiol 2006; 47: GISSI-2: a factorial randomised trial of altelase versus stretokinase and hearin versus no hearin among 2,490 atients with acute myocardial infarction. Gruo Italiano er lo Studio della Soravvivenza nell Infarto Miocardico. Lancet 990; 336: Prehosital thrombolytic theray in atients with susected acute myocardial infarction. The Euroean Myocardial Infarction Project Grou. N Engl J Med 993; 329: Schomig A, Ndreea G, Mehilli J, Schwaiger M, Schuhlen H, Nekolla S, Pache J, Martinoff S, Bollwein H, Kastrati A. Theray-deendent influence of time-to-treatment interval on myocardial salvage in atients with acute myocardial infarction treated with coronary artery stenting or thrombolysis. Circulation 2003; 08: Bode C, Smalling RW, Berg G, Burnett C, Lorch G, Kalbfleisch JM, Chernoff R, Christie LG, Feldman RL, Seals AA, Weaver WD. Randomized comarison of coronary thrombolysis achieved with double-bolus retelase (recombinant lasminogen activator) and frontloaded, accelerated altelase (recombinant tissue lasminogen activator) in atients with acute myocardial infarction. The RAPID II Investigators. Circulation 996; 94: Zeymer U, Tebbe U, Essen R, Haarmann W, Neuhaus KL. Influence of time to treatment on early infarct-related artery atency after different thrombolytic regimens. ALKK-Study Grou. Am Heart J 999; 37: Honan MB, Harrell FE Jr, Reimer KA, Califf RM, Mark DB, Pryor DB, Hlatky MA. Cardiac ruture, mortality and the timing of thrombolytic theray: a meta-analysis. J Am Coll Cardiol 990; 6: Moreno R, Loez-Sendon J, Garcia E, Perez de Isla L, Loez de Sa E, Ortega A, Moreno M, Rubio R, Soriano J, Abeytua M, Garcia- Fernandez MA. Primary angiolasty reduces the risk of left ventricular free wall ruture comared with thrombolysis in atients with acute myocardial infarction. J Am Coll Cardiol 2002; 39: Grines CL, Westerhausen DR Jr, Grines LL, Hanlon JT, Logemann TL, Niemela M, Weaver WD, Graham M, Boura J, O Neill WW, Balestrini C. A randomized trial of transfer for rimary angiolasty versus on-site thrombolysis in atients with high-risk myocardial infarction: the Air Primary Angiolasty in Myocardial Infarction study. J Am Coll Cardiol 2002; 39: Andersen HR, Nielsen TT, Rasmussen K, Thuesen L, Kelbaek H, Thayssen P, Abildgaard U, Pedersen F, Madsen JK, Grande P, Villadsen AB, Krusell LR, Haghfelt T, Lomholt P, Husted SE, Vigholt E, Kjaergard HK, Mortensen LS. A comarison of coronary angiolasty with fibrinolytic theray in acute myocardial infarction. N Engl J Med 2003; 349: Widimsky P, Budesinsky T, Vorac D, Groch L, Zelizko M, Aschermann M, Branny M, St asek J, Formanek P. Long distance transort for rimary angiolasty vs immediate thrombolysis in acute myocardial infarction. Final results of the randomized national multicentre trial--prague-2. Eur Heart J 2003; 24: