Upfront Thrombus Aspiration in Primary Coronary Intervention for Patients With ST-Segment Elevation Acute Myocardial Infarction

Transcription

1 JACC: CARDIOVASCULAR INTERVENTIONS VOL. 1, NO. 4, BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION ISSN /08/$34.00 PUBLISHED BY ELSEVIER INC. DOI: /j.jcin Ufront in Primary Coronary Intervention for Patients With ST-Segment Elevation Acute Myocardial Infarction Reort of the VAMPIRE (VAcuuM aspiration thrombus REmoval) Trial Yuji Ikari, MD, PHD, FACC,* Masami Sakurada, MD, Ken Kozuma, MD, PHD, Shigeo Kawano, MD, Takaaki Katsuki, MD, PHD, Kazuo Kimura, MD, Takahiko Suzuki, MD,# Takehiro Yamashita, MD, PHD,** Akinori Takizawa, MD, Kazuo Misumi, MD, Hideki Hashimoto, MD, PHD, Takaaki Isshiki, MD, FACC, for the VAMPIRE Investigators Isehara, Tokorozawa, Tokyo, Osaka, Shimotsuke, Yokohama, Toyohashi, Saoro, Shizuoka, and Matsudo, Jaan Objectives This study evaluated safety and efficacy of ufront thrombus asiration during rimary ercutaneous coronary intervention (PCI) in atients with ST-segment elevation myocardial infarction (STEMI). Background Distal embolization during rimary PCI results in reduced myocardial erfusion and oor clinical outcomes. Methods The VAMPIRE (VAcuuM aspiration thrombus REmoval) study was a rosective, randomized, controlled multicenter trial conducted in 23 institutions. Patients (N 355) resenting within 24 h of STEMI symtoms onset were randomized to rimary PCI with (n 180) or without (n 175) ufront thrombus asiration using Niro s TransVascular Catheter (Osaka, Jaan). Results The TransVascular Catheter reached the lesion in 100% of cases. It successfully crossed the target obstruction in 86% without any delay in rocedure time or time to reerfusion; whereas macroscoic thrombi were removed in 75% of the cases. Procedure success was similar between grous (98.9% vs. 98.3%). There was a trend toward lower incidence of slow or no reflow (rimary end oint defined as a Thrombolysis In Myocardial Infarction flow grade 3) in atients treated with asiration versus conventional rimary PCI (12.4% vs. 19.4%, 0.07). Rate of myocardial blush grade 3 was higher in the asiration grou (46.0% vs. 20.5%, 0.001). was most effective in atients resenting after 6hofsymtoms onset (slow flow rate: 8.1% vs. 37.6%, 0.01). Conclusions This study suggested the safety of rimary PCI with ufront thrombectomy using a novel device in atients with STEMI. The study showed a trend toward imroved myocardial erfusion and lower clinical events in atients treated with asiration. Patients resenting late after STEMI aear to benefit the most from thrombectomy. (J Am Coll Cardiol Intv 2008;1:424 31) 2008 by the American College of Cardiology Foundation From the *Deartment of Cardiology, Tokai University School of Medicine, Isehara, Jaan; Deartment of Cardiology, Tokorozawa Heart Clinic, Tokorozawa, Jaan; Deartment of Cardiology, Teikyo University School of Medicine, Tokyo, Jaan; Deartment of Cardiology, Sakurabashi Watanabe Hosital, Osaka, Jaan; Deartment of Cardiology, Jichi Medical University, Shimotsuke, Jaan; Deartment of Cardiology, Yokohama City University Medical Center, Yokohama, Jaan; #Deartment of Cardiology, Toyohashi Heart Center, Toyohashi, Jaan; **Deartment of Cardiology, Cardiovascular Center Hokkaido Ohno Hosital, Saoro, Jaan; Deartment of Cardiology, Shizuoka City Hosital, Shizuoka, Jaan; Deartment of Cardiology, Chiba West General Hosital, Matsudo, Jaan; and the Deartment of Health Economics and Eidemiology Research, University of Tokyo, Tokyo, Jaan. This study was funded by Niro. Manuscrit received January 9, 2008; revised manuscrit received Aril 23, 2008, acceted June 12, 2008.

2 JACC: CARDIOVASCULAR INTERVENTIONS, VOL. 1, NO. 4, Reerfusion theray in atients resenting with STsegment elevation myocardial infarction (STEMI) remains subotimal. Abnormal tissue-level myocardial erfusion has been shown to increase infarct size and reduce survival, in site of successful eicardial coronary reerfusion (1 7). Thus, aroaches to imrove results of rimary ercutaneous coronary intervention (PCI) have been roosed. Primary PCIs facilitated by various adjunctive harmacological theraies have been attemted, but the benefit of such strategies is questionable (8 10). The hyothesis that distal rotection or thrombectomy in addition to rimary PCI imrove myocardial salvage in atients with STEMI has also been attemted (11 13). Similarly, these studies failed to demonstrate a clear benefit of thrombectomy (11 13). The results of these revious investigations challenge our current understanding of the imortance of thrombus embolism as the cause of microvascular dysfunction and oor outcomes after reerfusion theray (14 19). Failure to effectively asirate materials, inadequate timing of deloyment of distal rotection devices or use of these devices without ufront asiration, and tyical learning curve for handling new devices articularly in emergency situations may have contributed to the erceived failure of thrombectomy strategies in revious studies. The TransVascular 180 Patients Assigned to Undergo PCI With Primary End Points 178 Included in Analysis of Angiograhical Myocardial Perfusion; Slow flow / no reflow, TIMI flow grade, blush score, ctfc Secondary End Points 115 Included in Analysis of ST-Segment Resolution 170 Included in Analysis of 8-m Major Adverse Cardiac Events 135 Included in Analysis of Follow-u Angiograhy and LVG at 6 m 93 Included in Analysis of BNP at 6 m Figure 1. Randomization Flow 355 Patients Randomized 175 Patients Assigned to Undergo PCI Without Primary End Points 171 Included in Analysis of Angiograhical Myocardial Perfusion; Slow flow / no reflow, TIMI flow grade, blush score, ctfc Secondary End Points 105 Included in Analysis of ST-Segment Resolution 158 Included in Analysis of 8-m Major Adverse Cardiac Events 135 Included in Analysis of Follow-u Angiograhy and LVG at 6 m 80 Included in Analysis of BNP at 6 m The figure indicates the atient randomization and flow of the VAMPIRE (VAcuuM aspiration thrombus REmoval) study. BNP brain natriuretic etide; ctfc corrected Thrombolysis in Myocardial Infarction frame count; LVG left ventriculograhy; PCI ercutaneous coronary intervention; TIMI Thrombolysis In Myocardial Infarction. Catheter (TVAC) (Niro, Osaka, Jaan) has a unique distal ti in the shae of a duck bill and ossesses a wide asiration lumen, which should imrove asiration erformance (20). This device has been tested reviously and showed good technical erformance (20). Thus, the resent study was lanned to evaluate the safety and efficacy of ufront thrombus asiration strategy using the novel TVAC device in atients with STEMI. Methods Study design and eligibility. The VAMPIRE (VAcuuM aspiration thrombus REmoval) study was a rosective randomized multicenter trial erformed in comliance with the rovisions of the Declaration of Helsinki regarding clinical investigations in humans. The study was aroved by the institutional review boards of all the investigational Abbreviations and Acronyms CK creatine kinase CK-MB creatine kinasemyocardial band ctfc corrected Thrombolysis In Myocardial Infarction frame count ECG electrocardiograhic/ electrocardiogram PCI ercutaneous coronary intervention STEMI ST-segment elevation myocardial infarction TIMI Thrombolysis In Myocardial Infarction TVAC TransVascular Catheter sites and written informed consent was obtained from all atients. Patients were enrolled from July 1, 2003, to January 1, 2005, and followed u to January 1, Patient randomization and study flow are shown in Figure 1. Individuals eligible for enrollment were 21 years old or older with acute myocardial infarction resenting more than 30 min but 24 h after symtom onset, with 2 mm or more of STsegment elevation in 2 or more contiguous leads or with a resumably new left bundle-branch block. Major criteria for exclusion were resence of rimary thrombolysis rior to randomization, cardiogenic shock, history of cardiac arrest, history of coronary byass surgery, chronic renal failure (Cr 2.0 mg/dl) or hemodialysis, left main disease, or target vessel 2.5 mm or 5 mm in diameter. There were no further exclusion criteria. PCI rocedure. Patients were retreated with asirin and intravenous hearin boluses were administered during the rocedure to maintain an activated clotting time 300 s. The PCI was erformed according to standard techniques with the use of 7-F guiding catheters. was erformed using TVAC, which is a single lumen raidexchange asiration shaft, comatible with 7-F guiding catheters and has a dedicated vacuum um (20). No asiration was erformed rior to or following PCI in the control grou. The use of bare metal stents was at the discretion of the attending hysicians and the goal was to achieve Thrombolysis In Myocardial Infarction (TIMI)

3 426 JACC: CARDIOVASCULAR INTERVENTIONS, VOL. 1, NO. 4, 2008 flow grade 3 with 10% residual stenosis. No drug eluting stents were allowed. Left ventriculograhy was erformed rior to PCI. The use of thrombolytic agents or glycorotein IIb/IIIa inhibitors was not allowed. Procedure success was defined as successful dilation of the target lesion to residual stenosis 50% without major adverse cardiac events. Post-PCI management. All atients received oral asirin and ticloidine. Cilostazol was allowed as an alternative agent to relace ticloidine in cases of intolerance. Patients were started on angiotensin-converting enzyme inhibitors within 24 h after the PCI and oral beta-blockers if not contraindicated. Study end oints. The rimary end oint of this study was the incidence of slow flow or no reflow during rimary PCI defined as a TIMI flow grade 3 not attributable to dissection, occlusive thrombus, or eicardial sasm that was evaluated by an indeendent core laboratory. Secondary end oints were coronary flow and myocardial erfusion immediately after PCI, as assessed by TIMI flow grade, corrected TIMI frame count (ctfc), and myocardial blush score. Other secondary end oints were time and magnitude of ST-segment resolution, eak creatine kinase (CK) and creatine kinase-myocardial band (CK-MB) measured every 8 h for 24 h after the rocedure, angiograhic in-stent late lumen loss at 6 months, left ventricular function as determined by angiograhy at 6 months, brain natriuretic etide levels at 6 months, and major adverse clinical events as a comosite of death, recurrence of myocardial infarction, and target lesion revascularization over 8 months. All atients were scheduled for angiograhic follow-u at 6 months and clinical visits at 1, 3, 6, and 8 months. Data analysis was erformed by an indeendent clinical research organization (Cardiocore Jaan, Tokyo, Jaan). Clinical events were adjudicated by an indeendent committee. Angiograhic analysis. Coronary angiograms were analyzed by an indeendent core laboratory (K. Kozuma, MD, at Cardiocore Jaan). Analysts were blinded to clinical data. Angiograhic TIMI flow grade was estimated visually, using standardized rocedures. The ctfc was measured with a frame counter on a digital film viewer analyzing the number of cine frames required for contrast to reach a standardized landmark. Results were corrected for 30 frames/s and the frame counts for the left anterior descending artery were divided by 1.7 because of the difference in length, as described reviously (21). In the resence of an occluded vessel (visual TIMI flow grade 0 to 1), ctfc was set to a value of 100. The occurrence of slow flow or no reflow (TIMI flow grade decreasing from 2 or 3 to 0 or 1 during the rocedure) was assessed. Myocardial blush grade was assessed immediately after the rocedure and at the 6-month follow-u. The TIMI flow, ctfc, and myocardial blush grade were assessed as described reviously (2,3,21,22), in each case by 2 exerienced analysts following secific standard oerating rocedures of the core laboratory. Interobserver variability of the blush score was 91% between the 2 analysts involved in this study. In cases of disagreement between assessments from different analysts, reassessment was erformed together until consensus was obtained. Quantitative coronary angiograhy and left ventriculograhy were erformed by means of QCA- Cardiovascular Measurement System, version 5.1 (MEDIS, Leiden, the Netherlands). Distal embolization was defined as the migration of a filling defect or the distal occlusion of the target vessel or 1 of its branches at the end of rocedure. Electrocardiograhic (ECG) analysis. A 12-lead ECG was acquired at admission, immediately after PCI, 3 to 6 h after PCI, at discharge, and 6 months after PCI. The ECG was analyzed by an indeendent core laboratory (Cardiocore Jaan). The ST-segment levels were measured 60 ms after the J oint in the most abnormal lead. The ercentage resolution of ST-segment elevation was categorized using the Schroder classification as comlete ( 70%), artial (30% to 70%), or absent ( 30%) (23,24). Statistical methods. The test hyothesis was that the incidence of the rimary end oint in the control grou is higher than in the study grou. We estimated a 25% incidence of slow flow or no reflow in the control grou, taking into consideration the range of reviously reorted data in similar oulations (23% to 37%) (1,25,26). We exected an 11% incidence of slow flow/no flow in the asiration grou, based on revious observations (27) and on our own unublished data. Thus, a total samle size of 171 atients in each arm would rovide 90% ower to detect a difference in the rimary end oint between grous ( 1 11%; 2 25%) using 2 grou chi-square tests with a sided significance level. Considering otential droouts during the study, the samle size in each arm was set at 175 atients. All analyses were erformed according to the intent-to-treat rincile. Categorical variables were resented as frequency values and were comared using the chi-square test. Continuous variables were exressed as mean standard deviation and were comared by using the Student t test. Results From July 1, 2003, to January 1, 2005, 362 atients were enrolled. Seven atients were excluded from the study after the enrollment: 2 because of errors in the diagnosis of STEMI, 2 withdrew the informed consent, and 3 atients were rotocol violations due to inadequate coronary artery diameters. A total of 355 atients with STEMI within 24 h of symtoms onset were randomized to receive either PCI with thrombus asiration using TVAC (n 180) or PCI alone (n 175) at 23 hositals in Jaan. Baseline clinical and angiograhic characteris-

4 JACC: CARDIOVASCULAR INTERVENTIONS, VOL. 1, NO. 4, tics were well matched between the 2 randomized grous (Tables 1 and 2). Procedural results. The TVAC reached the lesion in 100% of the atients as a rimary device, but oerators were able to cross the target obstruction with the TVAC without re-dilation in 83% of cases. In 3% of cases, device crossing was achieved after balloon dilation. The TIMI flow grade 2 or 3 immediately after asiration was achieved in 90.7% of atients randomized to asiration as comared with 47.4% after re-balloon wire maniulation in the control grou. There were no coronary erforations in either grou. There were no differences in rocedural success rate, time from catheterization laboratory door to TIMI flow grades 2 or 3, or rocedural time (Table 2). The incidence of coronary dissection and final distal embolism rate was significantly lower in the asiration grou. Macroscoic thrombus and/or laque debris were removed in 75.6% of cases (42.5% of red thrombus, 18.7% of white thrombus, 10.6% of red and white thrombus, and 3.1% of yellow laques and white thrombus). Myocardial reerfusion end oints. Angiograhic measures of myocardial erfusion were generally better in atients treated with thrombectomy and rimary PCI comared with standard theray (Table 3). The rimary end oint, rate of slow flow or no reflow, was achieved in 12.5% of atients in the asiration grou versus 19.4% in the control grou ( 0.07) (Table 3, Fig. 2). Myocardial blush grade was significantly better in the thrombus asiration grou comared with conventional rimary PCI ( 0.001). There was no significant difference in ST-segment resolution, eak CK or eak CK-MB release between the 2 grous (Table 3). Other angiograhic end oints. Data is resented in Table 4. Quantitative analyses of the target vessel and left ventricular Table 1. Baseline Clinical Characteristics Characteristics (n 180) No (n 175) Age, yrs Male gender, % Body mass index, kg/m Hyertension, % Hyerliidemia, % Diabetes, % Insulin use, % Smoking Current smoking, % Ex-smoker, % Family history of CAD, % Previous PCI, % Killi class 1, % Onset-to-hosital, h CAD coronary artery disease; PCI ercutaneous coronary intervention. Table 2. Baseline Angiograhic Data and Procedural Results (n 178) No (n 171) Target vessels, % 0.54 LAD LCX RCA Lesion tye, % 0.94 A B B C Baseline TIMI flow grade, % / Stent use, % IABP and/or PCPS use, % Transfemoral aroach, % GP IIb/IIIa inhibitors, % Procedural success, % Coronary dissection, % Distal embolism, % Vascular access comlication, % From ER door to TIMI 2 to 3, min From cath lab to TIMI 2 to 3, min Procedural time, min Fluoroscoy time, min ER emergency room; GP glycorotein; IABP intra-aortic balloon uming; LAD left anterior descending; LCX left circumflex; PCPS ercutaneous cardioulmonary suort; RCA right coronary artery; TIMI Thrombolysis In Myocardial Infarction. function at baseline or follow-u were similar between grous (Table 4). Brain natriuretic etide levels at 6 months showed a lower number in the asiration grou comared with the control, though the difference did not reach statistical significance. Clinical outcome. During hositalization, 1 atient died in each grou. Another atient had subacute thrombosis and comlicated reeat myocardial infarction in the control grou. The 8-month major adverse cardiac event rate was significantly lower in the thrombus asiration grou (12.9% vs. 21.0%, 0.05) mainly due to low target lesion revascularization rates in atients with late reerfusion of between 6 and 24 h (Table 5). Subgrou analysis of early and late reerfusion. Patients were stratified into an early ( 6 h from symtoms) and a late ( 6 h from symtoms) reerfusion. The strategy of thrombectomy and rimary PCI roduced consistent imrovement in all angiograhic and clinical outcome measures comared with conventional rimary PCI in atients resenting late after STEMI (Table 6).

5 428 JACC: CARDIOVASCULAR INTERVENTIONS, VOL. 1, NO. 4, 2008 Table 3. Angiograhic Assessment of Myocardial Perfusion, ST-Segment Resolution, and CK No Myocardial erfusion n 178 n 171 Slow flow/no reflow, % Final myocardial blush grade, % / Final TIMI flow grade, % Final ctfc ST-segment resolution, % (ostrocedural) n 115 n ST-segment resolution, % (3 to 6 h later) n 113 n Maximum CK (U/l) n 160 n 160 3,141 2,438 3,391 2, Maximum CK-MB subunit (U/l) n 110 n , CK creatine kinase; CK-MB creatine kinase-myocardial band; ctfc corrected TIMI flow count; other abbreviation as in Table 2. in atients treated with conventional rimary PCI without thrombectomy or distal rotection (1 3). In the ublished randomized studies so far, the AiMI (A Prosective, Randomized, Controlled Trial of Thrombectomy with the AngioJet in Acute Myocardial Infarction) trial tested the benefit of AngioJet as an adjunct to direct PCI in 480 atients with STEMI. The grou randomly assigned to the AngioJet grou had significantly larger infarct sizes, worse angiograhic measures, and a higher incidence of adverse clinical events than atients assigned to the usual care grou. Furthermore, the extensive use of acemakers might have contributed to oor outcomes increasing the risks of cardiac tamonade in the AiMI trial. In the VAMPIRE trial, the baseline infarct sizes and angiograhic measures were similar between the grous and acemaker use was not extensive. In the DEAR-MI (Dethrombosis to Enhance Acute Reerfusion in Myocardial Infarction) trial (28), the use of catheter thrombectomy in a randomized study of 148 atients with STEMI was associated with better myocardial reerfusion, lower CK release, lower risk of distal embolization, and lower risk of no reflow. The results of the DEAR-MI trial were consistent with the VAMPIRE study. In the X-AMINE ST (X-Sizer A non-tvac TVAC P=0.07 Discussion The strategy of rimary PCI with ufront thrombus asiration using the TVAC device may be safe and was associated with imroved clinical outcomes in the VAM- PIRE study. There was a trend toward better reerfusion arameters, including the rimary end oint of slow or no reflow henomena during PCI, among atients who underwent asiration. In articular, atients resenting between 6 and 24 h after symtoms onset aear to benefit the most from the thrombectomy strategy used in the resent study. This subgrou of atients exerienced better reerfusion arameters and lower incidence of adverse clinical events when treated with asiration as comared with conventional rimary PCI. The rate of slow or no reflow was 6 ercentage oints lower in the control oulation than anticiated, which may exlain the reduced statistical ower to detect statistical differences in the rimary end oint between grous. Recent studies reorted after the initiation of our trial have shown similarly low rates of slow flow rates (11% to 13%) B non-tvac TVAC slow flow / no reflow (%) P< % 20% 40% 60% 80% 100% Blush 0&1 Blush 2 Blush 3 Figure 2. Coronary Flow Immediately After the Procedure Figure shows the end oint results for the TransVascular Catheter (TVAC) grou versus non-tvac grou. (A) The rimary end oint of this study: comlication rate of slow flow or no reflow ( 0.07). (B) The secondary end oint: myocardial blush grade ( 0.001).

6 JACC: CARDIOVASCULAR INTERVENTIONS, VOL. 1, NO. 4, Table 4. QCA and LVG No QCA n 177 n 170 MLD re (mm) Reference re (mm) % stenosis re MLD ost (mm) Reference ost (mm) % stenosis ost QCA at 6-month follow-u n 135 n 135 MLD (mm) Reference (mm) % stenosis Late loss (mm) Binary restenosis rate, % LVG n 145 n 139 EDVI (ml/m 2 ) ESVI (ml/m 2 ) EF (%) LVG at 6-month follow-u n 103 n 113 EDVI (ml/m 2 ) ESVI (ml/m 2 ) EF (%) BNP at 6-month follow-u n 93 n 80 BNP BNP brain natriuretic etide; EDVI end-diastolic volume index; EF ejection fraction; ESVI end-systolic volume index; LVG left ventriculograhy; MLD minimum lumen diameter; QCA quantitative coronary angiograhy. in Acute Myocardial Infarction Patients for Negligible Embolization and Otimal ST Resolution) trial (29), The adjunctive use of X-Sizer was evaluated before PCI in 201 Table 5. Clinical Outcome In-Hosital and at 8-Month Follow-U No In-hosital n 178 n 171 MACE 1 (0.6%) 2 (1.2%) NS Death 1 1 NS MI 0 1 (SAT) NS TLR 0 1 NS PCI 0 1 NS CABG 0 0 NS 8-month follow-u n 170 n 158 MACE 22 (12.9%) 33 (20.9%) 0.05 Death 2 1 NS MI 0 1 NS TLR PCI CABG 2 1 NS CABG coronary artery byass grafts; MACE major adverse cardiac events; MI myocardial infarction; SAT subacute thrombosis; TLR target lesion revascularization; other abbreviations as in Table 1. Table 6. Subgrou Analysis of Early and Late Reerfusion on Primary End Points No Slow flow/no reflow Early reerfusion 12.2% (n 123) 15.3% (n 111) 0.38 Late reerfusion 8.1% (n 36) 37.6% (n 41) 0.01 Final myocardial blush grade 3, % Early reerfusion 43.9% (n 123) 18.9% (n 111) Late reerfusion 51.4% (n 35) 21.9% (n 41) 0.03 Final TIMI flow grade 3, % Early reerfusion 87.8% (n 123) 84.7% (n 111) 0.38 Late reerfusion 91.9% (n 36) 63.4% (n 41) 0.01 Final ctfc Early reerfusion (n 121) (n 111) 0.34 Late reerfusion (n 35) (n 40) 0.04 TLR (PCI or CABG) Early reerfusion 11.8% (n 119) 17.2% (n 105) 0.25 Late reerfusion 9.1% (n 33) 29.7% (n 37) 0.03 MACE Early reerfusion 13.5% (n 119) 18.1% (n 105) 0.34 Late reerfusion 12.1% (n 33) 32.4% (n 37) 0.04 Early reerfusion included atients who arrived at hosital within 6 h from the onset. Late reerfusion included atients who arrived at hosital from 6hto24hfrom the onset. Abbreviations as in Tables 1, 2, 3, and 5 atients with myocardial infarctions of 12-h duration. The rimary end oint of this study was the magnitude of ST-segment resolution at 1 h, which was imroved in the X-Sizer grou comared with the conventional theray grou (7.5 mm vs. 4.9 mm, 0.033). Although the occurrence of distal embolization was reduced with the use of X-Sizer (2% vs. 10%), equivalent rates were seen for TIMI flow grade 3, myocardial blush grade 3, and 6-month major adverse cardiac and cerebral events. In the X-TRACT (Prosective Randomized Trial of Thromboatherectomy with the X-Sizer in Native Coronary Arteries and Sahenous Vein Grafts) study (30), a total of 797 consecutive atients undergoing stent imlantation in vein grafts (72%) or native coronary artery containing thrombus (28%) were rosectively randomized to X-Sizer catheter or to usual care followed by PCI grous. The rates of no reflow, distal emboli, myocardial infarction, as well as 30-day rate of major adverse cardiac events were similar between the grous. Desite of the marginal 36% difference in the incidence of the rimary end oint between grous, the VAMPIRE study showed several otential benefits of the ufront asiration as reorted in other studies (31 33). The TIMI flow grades 2 or 3 were achieved in 90% of cases immediately after asiration, which may facilitate selection of PCI device sizes as it rovides early information about the size of distal artery as well as location and length of the target

7 430 JACC: CARDIOVASCULAR INTERVENTIONS, VOL. 1, NO. 4, 2008 lesion. The higher incidence of TIMI flow after asiration may also hel exlain the lower coronary dissection observed in the treatment arm. The rocedure time or time to reerfusion was not affected by the use of 1 additional device in the TVAC grou. The time to erform thrombectomy and rimary PCI in the resent study is relatively shorter than in revious reorts, which may exlain the difference in outcomes between studies (11 13,29). Furthermore, there was a high rate of macroscoic thrombus or laque debris asirated in our study. The flexibility, low crossing rofile, and the activation of suction during insertion of the TVAC catheter rior to crossing the obstruction, may have resulted in lower distal embolism in this study. Although a major adverse clinical event was not a rimary end oint of this study, the 38% reduction in the incidence of clinical events, rimarily due to lower target lesion revascularization rates, observed in the asiration grou is noticeable. Whether removal of inflammatory debris and active thrombus material from the target lesion rior to stenting exlain the low clinical restenosis rates observed in the resent study remains to be confirmed by studies roerly designed to test such a hyothesis. Finally, our study rovides strong ilot evidence that atients resenting late after symtoms onset benefit the most from ufront thrombectomy during rimary PCI. Conventional rimary PCI in this subgrou is associated with worse outcomes than in those resenting earlier after symtoms (34). Conversely, angiograhic and clinical outcomes were essentially equalized between early and late reerfusion atients when both oulations were treated with a strategy of ufront thrombectomy rior to rimary PCI. Study limitations. Not using glycorotein IIb/IIIa inhibitors may be a limitation of this study because their use could influence outcomes whose athogenesis involves latelet thrombi. However, the use of glycorotein IIb/IIIa inhibitors has not uniformly roduced enhanced clinical outcomes in clinical trials (35). Future studies could investigate the interaction between glycorotein IIb/IIIa inhibitors and thrombectomy devices in the setting of STEMI. Conclusions The VAMPIRE study showed the marginal benefit of thrombectomy on myocardial erfusion. In a ost hoc analysis, atients with late reerfusion of between 6 and 24 h benefited most from the thrombectomy. The effectiveness of thrombectomy for STEMI may deserve reevaluation with a simle ufront thrombus asiration strategy using an efficient device in a refined study design. The study was not designed, and consequently is underowered, to detect major differences in isolated clinical end oints such as myocardial infarction and death. Our data may not aly to the overall oulation resenting with STEMI as differences in secific technical asects of the rocedure, such as time to balloon inflation, asiration devices, and mode of asiration may differ between institutions and countries. Nevertheless, our results suort the concet that ufront thrombectomy in atients with acute STEMI undergoing rimary PCI is safe and may imrove acute reerfusion and clinical outcomes, articularly in atients resenting later after symtoms onset. Taken together, the knowledge accumulated with other studies investigating similar hyotheses and the resent data warrant further attemts to develo rheolytic strategies to imrove outcomes of the high-risk oulation resenting with STEMI. Rerint requests and corresondence: Dr. Takaaki Isshiki, Deartment of Cardiology, Teikyo University School of Medicine, , Kaga, Itabashi-ku, Tokyo , Jaan. isshiki@med.teikyo-u.ac.j. REFERENCES 1. Ito H, Tomooka T, Sakai N, et al. Lack of myocardial erfusion immediately after successful thrombolysis. A redictor of oor recovery of left ventricular function in anterior myocardial infarction. Circulation 1992;85: van t Hof AW, Liem A, Suryaranata H, Hoorntje JC, de Boer MJ, Zijlstra F; on behalf of Zwolle Myocardial Infarction Study Grou. Angiograhic assessment of myocardial reerfusion in atients treated with rimary angiolasty for acute myocardial infarction: myocardial blush grade. Circulation 1998;97: Stone GW, Peterson MA, Lansky AJ, Dangas G, Mehran R, Leon MB. Imact of normalized myocardial erfusion after successful angiolasty in acute myocardial infarction. J Am Coll Cardiol 2002; 39: Henriques JP, Zijlstra F, Ottervanger JP, et al. Incidence and clinical significance of distal embolization during rimary angiolasty for acute myocardial infarction. Eur Heart J 2002;23: Wu KC, Zerhouni EA, Judd RM, et al. Prognostic significance of microvascular obstruction by magnetic resonance imaging in atients with acute myocardial infarction. Circulation 1998;97: van t Hof AW, Liem A, de Boer MJ, Zijlstra F; on behalf of Zwolle Myocardial infarction Study Grou. Clinical value of 12-lead electrocardiogram after successful reerfusion theray for acute myocardial infarction. Lancet 1997;350: Claeys MJ, Bosmans J, Veenstra L, Jorens P, De Raedt H, Vrints CJ. Determinants and rognostic imlications of ersistent ST-segment elevation after rimary angiolasty for acute myocardial infarction: imortance of microvascular reerfusion injury on clinical outcome. Circulation 1999;99: Gabriel RS, White HD. ExTRACT-TIMI 25 trial: clarifying the role of enoxaarin in atients with ST-elevation myocardial infarction receiving fibrinolysis. Exert Rev Cardiovasc Ther 2007;5: Sabatine MS, McCabe CH, Gibson CM, Cannon CP. Design and rationale of Cloidogrel as Adjunctive Reerfusion Theray- Thrombolysis In Myocardial Infarction (CLARITY-TIMI) 28 trial. Am Heart J 2005;149: Ellis SG, Armstrong P, Betriu A, et al.; on behalf of the FINESSE Investigators. Facilitated ercutaneous coronary intervention versus rimary ercutaneous coronary intervention: design and rationale of the Facilitated Intervention with Enhanced Reerfusion Seed to Sto Events (FINESSE) trial. Am Heart J 2004;147:E Stone GW, Webb J, Cox DA, et al. Distal microcirculatory rotection during ercutaneous coronary intervention in acute ST-segment elevation myocardial infarction: a randomized controlled trial. JAMA 2005;293:

8 JACC: CARDIOVASCULAR INTERVENTIONS, VOL. 1, NO. 4, Ali A, Cox D, Dib N, et al. Rheolytic thrombectomy with ercutaneous coronary intervention for infarct size reduction in acute myocardial infarction: 30-day results from a multicenter randomized study. J Am Coll Cardiol 2006;48: Kaltoft A, Bottcher M, Nielsen SS, et al. Routine thrombectomy in ercutaneous coronary intervention for acute ST-segment-elevation myocardial infarction: a randomized, controlled trial. Circulation 2006; 114: Saber RS, Edwards WD, Bailey KR, McGovern TW, Schwartz RS, Holmes DR Jr. Coronary embolization after balloon angiolasty or thrombolytic theray: an autosy study of 32 cases. J Am Coll Cardiol 1993;22: Kloner RA, Rude RE, Carlson N, Maroko PR, DeBoer LW, Braunwald E. Ultrastructural evidence of microvascular damage and myocardial cell injury after coronary artery occlusion: which comes first? Circulation 1980;62: Gavin JB, Thomson RW, Humhrey SM, Herdson PB. Changes in vascular morhology associated with the no-reflow henomenon in ischaemic myocardium. Virchows Arch A Pathol Anat Histoathol 1983;399: Michaels AD, Gibson CM, Barron HV. Microvascular dysfunction in acute myocardial infarction: focus on the roles of latelet and inflammatory mediators in the no-reflow henomenon. Am J Cardiol 2000;85:50B 60B. 18. Engler RL, Dahlgren MD, Morris DD, Peterson MA, Schmid- Schonbein GW. Role of leukocytes in resonse to acute myocardial ischemia and reflow in dogs. Am J Physiol 1986;251:H Tool EJ, Yadav JS. Recognition of the imortance of embolization in atherosclerotic vascular disease. Circulation 2000;101: Sakurada M, Ikari Y, Isshiki T. Imroved erformance of a new thrombus asiration catheter: outcomes from in vitro exeriments and a case resentation. Catheter Cardiovasc Interv 2004;63: Gibson CM, Cannon CP, Daley WL, et al. TIMI frame count: a quantitative method of assessing coronary artery flow. Circulation 1996;93: Gibson CM, Cannon CP, Murhy SA, et al. Relationshi of TIMI myocardial erfusion grade to mortality after administration of thrombolytic drugs. Circulation 2000;101: Schroder R, Dissmann R, Bruggemann T, et al. Extent of early ST-segment elevation resolution: a simle but strong redictor of outcome in atients with acute myocardial infarction. J Am Coll Cardiol 1994;24: Schroder R, Wegscheider K, Schroder K, Dissmann R, Meyer- Sabellek W. Extent of early ST-segment elevation resolution: a strong redictor of outcome in atients with acute myocardial infarction and a sensitive measure to comare thrombolytic regimens. A substudy of the International Joint Efficacy Comarison of Thrombolytics (IN- JECT) trial. J Am Coll Cardiol 1995;26: Loubeyre C, Morice MC, Lefevre T, Piechaud JF, Louvard Y, Dumas P. A randomized comarison of direct stenting with conventional stent imlantation in selected atients with acute myocardial infarction. J Am Coll Cardiol 2002;39: Ito H, Maruyama A, Iwakura K, et al. Clinical imlications of the no reflow henomenon. A redictor of comlications and left ventricular remodeling in reerfused anterior wall myocardial infarction. Circulation 1996;93: Kotani J, Nanto S, Mintz GS, et al. Plaque gruel of atheromatous coronary lesion may contribute to the no-reflow henomenon in atients with acute coronary syndrome. Circulation 2002;106: Silva-Orrego P, Colombo P, Bigi R, et al. asiration before rimary angiolasty imroves myocardial reerfusion in acute myocardial infarction: the DEAR-MI (Dethrombosis to Enhance Acute Reerfusion in Myocardial Infarction) study. J Am Coll Cardiol 2006;48: Lefevre T, Garcia E, Reimers B, et al. X-Sizer for thrombectomy in acute myocardial infarction imroves ST-segment resolution: results of the X-Sizer in AMI for negligible embolization and otimal ST resolution (X AMINE ST) trial. J Am Coll Cardiol 2005;46: Stone GW, Cox DA, Low R, et al.; on behalf of the X-tRACT Investigators. Safety and efficacy of a novel device for treatment of thrombotic and atherosclerotic lesions in native coronary arteries and sahenous vein grafts: results from the multicenter X-Sizer for treatment of thrombus and atherosclerosis in coronary alications trial (X-TRACT) study. Catheter Cardiovasc Interv 2003;58: Cohen R, Domniez T, Foucher R, Sfaxi A, Elhadad S. Intracoronary thrombectomy with the exort asiration catheter before angiolasty in atients with ST-segment elevation myocardial infarction. J Interv Cardiol 2007;20: Antoniucci D, Valenti R, Migliorini A, et al. Comarison of rheolytic thrombectomy before direct infarct artery stenting versus direct stenting alone in atients undergoing ercutaneous coronary intervention for acute myocardial infarction. Am J Cardiol 2004;93: Burzotta F, Trani C, Romagnoli E, et al. Manual thrombus-asiration imroves myocardial reerfusion: the randomized evaluation of the effect of mechanical reduction of distal embolization by thrombusasiration in rimary and rescue angiolasty (REMEDIA) trial. J Am Coll Cardiol 2005;46: Cohen M, Gensini GF, Maritz F, et al.; on behalf of TETAMI Investigators. Prosective evaluation of clinical outcomes after acute ST-elevation myocardial infarction in atients who are ineligible for reerfusion theray: reliminary results from the TETAMI registry and randomized trial. Circulation 2003;108:III Stone GW, Grines CL, Cox DA, et al. Comarison of angiolasty with stenting, with or without abciximab, in acute myocardial infarction. N Engl J Med 2002;346: Key Words: ST-segment elevation myocardial infarction thrombectomy coronary flow. APPENDIX For a list of the VAMPIRE Investigators, lease see the online version of this article.