Methods. Patients and clinical centers. To examine the short- and long-term outcomes of holmium laser-facilitated balloon an-

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1 1714 JACC Vol. 30, No. 7 Prosective, Randomized, Multicenter Comarison of -Facilitated Balloon Angiolasty Versus Stand-Alone Balloon Angiolasty in Patients With Obstructive Coronary Artery Disease GREGG W. STONE, MD, FACC, EDUARDO DE MARCHENA, MD, FACC,* DAVID DAGEFORDE, MD, FACC, ALBERTO FOSCHI, MD, FACC, JOSEPH B. MUHLESTEIN, MD, FACC, MICHAEL MCIVOR, MD, FACC, DAVID RIZIK, MD, FACC, RONALD VANDERLAAN, MD, FACC,# JOANN MCDONNELL, RN, MA, FOR THE LASER ANGIOPLASTY VERSUS ANGIOPLASTY (LAVA) TRIAL INVESTIGATORS** Mountain View, California; Miami and St. Petersburg, Florida; Louisville, Kentucky; Evanston, Illinois; Salt Lake City, Utah; Scottsdale, Arizona; and Grand Raids, Michigan Objectives. The goal of this study was to examine the relative safety and efficacy of laser-facilitated ercutaneous transluminal coronary angiolasty () versus stand-alone. Background. Plaque debulking with lasing before may result in imroved lumen dimensions and decreased rates of erirocedural ischemic comlications, thus imroving shortand long-term outcomes after ercutaneous intervention. The mid-infrared holmium:yttrium-aluminum-garnet (YAG) laser has been shown to be effective in a variety of laque subtyes and may be articularly useful in high risk acute ischemic syndromes. Methods. A total of 215 atients (mean [ SD] age years) with 244 lesions were rosectively randomized at 14 clinical centers to laser versus stand-alone. After laser treatment, all atients underwent ; 148 atients (69%) had unstable angina. Results. The rocedural success rate without major catheterization laboratory comlications was similar in atients assigned to laser treatment or alone (96.6% vs. 96.9%, 0.88), as was the in-hosital clinical success rate (89.7% vs. 93.9%, 0.27). There was no difference in ostrocedural diameter stenosis after laser treatment comared with (18.3% 13.6% vs. 19.5% 15.1%, 0.50). However, use of the laser, versus alone, did result in significantly more major and minor rocedural comlications (18.0% vs. 3.1%, ), myocardial infarctions (4.3% vs. 0%, 0.04) and total in-hosital major adverse events (10.3% vs. 4.1%, 0.08). At a mean follow-u time of months, there were no differences in late or event-free survival in atients assigned to laser treatment versus alone. Conclusions. Comared with stand-alone, laserfacilitated results in a more comlicated hosital course, without immediate or long-term benefits. (J Am Coll Cardiol 1997;30: ) 1997 by the American College of Cardiology Desite advances in equiment and technique, ercutaneous transluminal coronary angiolasty () continues to be associated with an aroximate 4% to 10% risk of major erirocedural comlications and a 30% to 50% likelihood of From the Cardiovascular Institute, El Camino Hosital, Mountain View, California; *University of Miami/Jackson Memorial Hosital, Miami, Florida; Audubon Hosital, Louisville, Kentucky; St. Francis Hosital, Evanston, Illinois; LDS Hosital, Salt Lake City, Utah; All Children s Hosital, St. Petersburg, Florida; Scottsdale Memorial Hosital, Scottsdale, Arizona; and #Blodgett Memorial Medical Center, Grand Raids, Michigan. **A comlete list of the articiating institutions and investigators for the LAVA trial aears in the Aendix. Funding for this study was rovided in art by Eclise Surgical Technologies, Inc., Sunnyvale, California. Manuscrit received June 5, 1997; revised manuscrit received August 27, 1997, acceted Setember 2, Address for corresondence: Dr. Gregg W. Stone, The Cardiovascular Institute, 2660 Grant Road, Mountain View, California gstone1418@aol.com. angiograhic restenosis within 6 months, which frequently necessitates late reeat revascularization rocedures (1 5). By removing laque before balloon dilation, debulking techniques, such as laser or atherectomy, may otentially diminish the rate of -induced major dissection and comlications and imrove late angiograhic and clinical outcomes. In this regard, both the excimer and holmium lasers have been shown in large, rosective registry exeriences to have favorable success rates in most lesion subtyes comared with balloon angiolasty (6 10). We therefore erformed a rosective, randomized, multicenter trial to examine the acute and late outcomes of laser-facilitated versus standard. Methods Patients and clinical centers. To examine the short- and long-term outcomes of holmium laser-facilitated balloon an by the American College of Cardiology /97/$17.00 Published by Elsevier Science Inc. PII S (97)

2 JACC Vol. 30, No. 7 STONE ET AL. LASER ANGIOPLASTY VS. STAND-ALONE ANGIOPLASTY 1715 Abbreviations and Acronyms ACC/AHA American College of Cardiology/American Heart Association AMRO Amsterdam Rotterdam (trial) CK creatine kinase ECG electrocardiogram FDA Food and Drug Administration LAVA Angiolasty Versus Angiolasty (trial) MI myocardial infarction OR odds ratio ercutaneous transluminal coronary angiolasty TIMI Thrombolysis in Myocardial Infarction giolasty versus stand-alone, 14 centers exerienced in the use of the Eclise Holmium 2100 laser entered atients in a rosective, randomized trial. The rimary end oint was the 6-month comosite incidence of freedom from death, myocardial infarction (MI) or need for coronary artery byass graft surgery or reeat. With an alha error of 0.05 and a beta error of 0.20, 190 randomized atients with comlete follow-u were required to show an imrovement in the rimary end oint from an exected rate of 70% after standalone to 85% after laser-facilitated. Entry criteria were nonrestrictive and included atients 18 years old, with no uer age limit, with rimary or restenotic lesions in a native coronary artery or sahenous vein byass graft. The first 10 sites enrolled atients with stable or unstable angina. After the demonstration that the holmium laser may be articularly effective in atients with acute ischemic syndromes (7,11,12), an additional four sites were added that randomized atients with unstable angina only. Patients resenting with an acute MI within 24 h of the rocedure were excluded. Patients were also excluded for secific laser contraindications, including an index lesion that was on a bend 60, if the reference segment was 2.0 mm in diameter or if excessive roximal tortuosity or heavy calcification was resent, making it unlikely that the catheter could be delivered to or cross the stenosis. The resence of a chronic total occlusion was not an exclusion criteria itself; however, randomization occurred only after the lesion was successfully crossed with a guide wire, and thus nonrecanalizable total occlusions were excluded. This rotocol was aroved by the Food and Drug Administration (FDA) as art of the regulatory athway for market authorization for the holmium laser. Written informed consent was obtained from all atients before enrollment after local investigational review board aroval. Study rotocol. Patients were retreated with 324 mg of asirin daily for 24 h and calcium channel blocking agents. Other medications before cardiac catheterization were dictated by clinical resentation. After left ventriculograhy and coronary arteriograhy, if suitable coronary anatomy was resent for study entry, randomization occurred by oening a sealed enveloe after the index lesion was successfully wired. If multile target lesions were resent, all lesions must have met entry criteria and were aroached by the assigned modality. Intravenous hearin was administered to maintain an activated clotting time 350 s. Intracoronary nitroglycerin ( 100 g) was given before intervention. If randomization was to, balloons were chosen to aroximate the reference vessel size, and dilation was erformed with a goal of 30% residual stenosis without major dissection. If randomization was to laser treatment, lasing was erformed as described in the next section, followed by in all atients to maximize the final lumen dimension. After the rocedure, the sheaths were removed in 6 to 12 h, and atients were discharged when in clinically stable condition. Calcium channel blockers were rescribed for 1 month and asirin indefinitely. Clinical follow-u was scheduled for 1, 3 and 6 months after the rocedure. system and rocedure. The holmium:yttriumaluminum-garnet (YAG) Eclise 2100 (Eclise Surgical Technologies) is a ulsed, solid state, mid-infrared laser that has been used in 1,862 atients since 1990 under an Investigational Device Exemtion (IDE) from the FDA. light with a wavelength of 2.09 m is transmitted through multile otical low OH flexible silica fibers and emitted from the distal ti of the catheter after foot edal activation. The device delivers 5 ulses/s with a ulse duration of 250 s with an energy range of 250 to 1,000 mj/ulse (1.25 to 5.0 W). The energy density (fluence) at the ti of the catheter is 125 to 500 mj/mm 2 er ulse. The tissue enetration deth is 400 m. Six different catheter sizes (1.2, 1.3, 1.4, 1.5, 1.7 and 2.0 mm) are manufactured that vary in diameter, number of fibers er catheter and flexibility. The 1.2- to 1.5-mm diameter catheters are comatible with an 8F guide catheter, whereas the larger devices require a 9F guide. All catheters traverse over a in. guide wire. The choice of laser variables (catheter size and energy range) was left to the discretion of the oerator. In general, the smaller diameter catheters are initially chosen for severe lesions. The laser is reared by flushing the central guide wire lumen and connecting the roximal end to the laser console. The device is then turned on and left in standby mode. No warm-u eriod or other calibrations are required. The catheter is then assed over the guide wire just roximal to the lesion and laced in active mode. The ulse and retreat technique is used for crossing the lesion (13), in which only a small number of ulses, usually 8 to 12 er session, are used with gentle forward ressure being alied to the catheter under fluoroscoy. The catheter is then withdrawn into the roximal artery or guide catheter for 30 to 60 s to allow heat dissiation and gas bubble disersion. The catheter is then readvanced to the lesion, and serial asses are made with similar technique. Tyically, lower energy fluences are initially selected and are then increased if adequate ablation is not occurring. Reeat arteriograhy, after intracoronary nitroglycerin, was erformed after the last laser ass. The maximal laser catheter diameter and fluence, total number of ulses and total lasing time were recorded.

3 1716 STONE ET AL. JACC Vol. 30, No. 7 LASER ANGIOPLASTY VS. STAND-ALONE ANGIOPLASTY Definitions. Unstable angina was defined as new-onset, crescendo, rest or ostinfarction angina. For the urose of this study, laser success was defined as the ability of the laser to comletely cross the lesion and reduce the stenosis by 20%. Procedural success was defined as 50% residual stenosis after, without major catheterization laboratory comlication (death, emergency byass surgery or sustained coronary occlusion). Anterograde flow was assessed by the Thrombolysis in Myocardial Infarction (TIMI) scale (14). Lesion morhology was characterized by the modified American College of Cardiology/American Heart Association (ACC/AHA) score (15). Thrombus was defined as an intraluminal filling defect, lucency or haziness refractory to intracoronary nitroglycerin. Coronary sasm was defined as transient reduction in blood flow with vessel caliber narrowing relieved either sontaneously or by nitroglycerin. Abrut closure was defined as sustained TIMI flow grade 0 to 1 caused by obstruction of the target lesion. Q wave MI was defined as elevation of creatine kinase (CK) levels greater than two times above laboratory normal values with any abnormal MB fraction and the develoment of new athologic Q waves on the electrocardiogram (ECG). A non-q wave MI was defined as the develoment of similar CK elevations without Q waves. Clinical success was defined when a residual stenosis 50% was obtained, and the atient survived the hosital eriod without an MI (Q wave or non Q wave) or need for reeat or byass surgery. Data collection and statistical analysis. Detailed inhosital and 1- and 6-month follow-u case reort forms were rosectively comleted for each atient and confirmed by review of catheterization reorts, ECGs laboratory tests and discharge summaries. A study monitor traveled to each site for indeendent verification of case reort form accuracy. Adverse events were reorted to the clinical coordinating center within 24 h of occurrence. Angiograms were evaluated by individual oerators using digital caliers or visual assessment. Data was entered into a comuterized database, and statistical analysis was erformed with commercially available ackages (Statview 4.5, Abacus Concets and JMP 3.1, SAS Institute). Intention to treat analysis was erformed. Categoric variables were comared with chi-square or Fisher exact tests, and continuous variables were comared with an unaired Student t test. To determine the indeendent correlates of rocedural and clinical success, several variables known to affect outcomes were entered into a multile logistic regression model (age, gender, diabetes, trile-vessel disease, treatment of any thrombotic lesion, any total occlusion, any ACC/AHA class C lesion, reference vessel size 3.0 mm or 3.0 mm in diameter, as well as randomization arm). Follow-u events were analyzed with actuarial methods, and Kalan-Meier curves were constructed. Differences in late events among atients undergoing laser angiolasty versus stand alone were comared with the log rank test. Variables affecting late and event-free survival were examined using Cox roortional hazards regression analysis. A value 0.05 was required for statistical significance. Table 1. Baseline Clinical Characteristics of 215 Study Patients (n 117) (n 98) Age (yr) Female gender 31.6% 30.6% 0.78 Hyertension 59.8% 59.2% 0.87 Hyercholesterolemia 48.2% 46.8% 0.91 Diabetes mellitus 19.7% 27.6% 0.22 Cigarette use 57.2% 54.6% 0.65 Silent ischemia 3.4% 5.1% 0.76 Chronic stable angina 27.4% 26.5% 0.82 Unstable angina 69.2% 68.4% 0.89 Pain only with MI 12.0% 17.4% 0.26 Postinfarction angina 9.4% 3.1% 0.09 Prior MI 53.8% 35.7% Prior CHF 6.0% 8.2% 0.53 Prior 27.4% 33.7% 0.29 Prior CABG 10.3% 12.2% 0.63 Data resented are mean value SD or ercent of atients. CABG coronary artery byass graft surgery; CHF congestive heart failure; MI myocardial infarction; ercutaneous transluminal coronary angiolasty. Results Patients. A total of 215 atients were randomized at 14 centers, with 244 lesions treated. There were no major differences in baseline demograhic characteristics in atients assigned to laser or standard, excet for a higher incidence of revious MI in laser-treated atients (Table 1). Baseline angiograhic characteristics were also well matched among the two treatment grous, excet that lesions assigned to laser treatment were more likely to have thrombus resent (Tables 2 and 3). Table 2. Baseline Angiograhic Characteristics of 244 Treated Lesions in 215 Patients Patients n 117 n 98 LVEF (%) No. of diseased eicardial vessels % 66.3% % 19.4% % 14.3% 0.37 Lesions n 125 n 119 IRA distribution LAD 26.0% 30.7% 0.42 LCx 24.4% 42.1% 0.62 RCA 49.6% 27.2% 0.25 Infarct lesion location Proximal vessel 29.3% 31.6% 0.70 Midvessel 43.1% 36.8% 0.33 Distal vessel or branch 27.6% 31.6% 0.51 Data resented are mean value SD or number or ercent of atients or lesions. IRA infarct-related artery; LAD left anterior descending coronary artery; LCx left circumflex coronary artery; LVEF left ventricular ejection fraction; ercutaneous transluminal coronary angiolasty; RCA right coronary artery.

4 JACC Vol. 30, No. 7 STONE ET AL. LASER ANGIOPLASTY VS. STAND-ALONE ANGIOPLASTY 1717 Table 3. Baseline Angiograhic Lesion Morhology (n 125) (n 119) ACC/AHA classification A 13.6% 25.2% B1 16.8% 16.8% B2 55.2% 46.2% 0.16 C 14.4% 11.8% Lesion length (mm) mm 43.5% 42.4% 0.79 Eccentric 52.0% 43.2% 0.17 Proximal tortuosity 27.2% 21.2% 0.52 Angulated segment % 12.1% 0.27 Irregular contour 52.4% 43.6% 0.17 Calcification resent 17.1% 13.6% 0.45 Total occlusion 9.6% 5.0% 0.18 Ostial location 0.8% 2.5% 0.36 Bifurcation lesion 4.0% 5.9% 0.48 Thrombus resent 26.8% 14.4% 0.02 Degenerated sahenous vein graft 1.6% 0% 0.55 Data resented are mean value SD or ercent of lesions. ACC/AHA American College of Cardiology/American Heart Association; ercutaneous transluminal coronary angiolasty. Procedural outcome. Among atients randomized to laser angiolasty, the laser catheter reached the lesion and was activated in 122 (98%) of 125 lesions. success was achieved in 117 lesions (93.6%), whereas the laser artially enetrated the lesion in 3 lesions (2.4%). Mean ( SD) catheter size was mm, and a mean of catheters were used er atient. A mean of ulses were alied er lesion, at maximal mean energy of W. was erformed in all atients assigned to laser treatment. Reference vessels were judged to be slightly larger in the laser-treated atients than the -treated atients. This difference was comensated for by use of larger balloons in atients assigned to laser treatment, and thus the balloon/ artery ratio was identical between the two grous (Table 4). There were no other significant differences in variables in atients randomized to laser-facilitated versus stand-alone (Table 4). The results of the quantitative angiograhic analysis are shown in Table 5. By on-site assessment, baseline lesion Table 4. Coronary Angiolasty Variables for 244 Lesions (n 125) (n 119) Balloons/lesion Inflations/lesion Ref seg diam (mm) Max balloon size (mm) Balloon/artery ratio Total inflation time (min) Max ressure (atm) Data resented are mean value SD. Max maximal; ercutaneous transluminal coronary angiolasty; Ref seg diam reference segment diameter. Table 5. Quantitative Angiograhic Analysis (n 125) (n 119) Ref seg diam (mm) MLD (mm) Before intervention After laser After %DS Before intervention After laser After Data resented are mean value SD. MLD minimum lumen diameter; %DS ercent diameter stenosis; not alicable; other abbreviations as in Table 4. severity was slightly worse in atients assigned to laser angiolasty than in those with stand-alone. However, there was no difference in the final ost- residual stenosis between the two grous, although the absolute minimal lumen diameter was slightly greater in the laser-treated atients, given the larger baseline mean reference vessel diameter. Dissection was noted in only 5.6% of atients immediately after laser treatment. However, the frequency of dissection after laser-facilitated was similar to that after standalone (16.8% vs. 15.9%, resectively, 0.85). Procedural success without major catheterization laboratory comlications was obtained in 96.6% of laser-treated atients versus 96.9% of -treated atients ( 0.88). The only variable indeendently redictive of rocedural failure in the multivariate model was the resence of trilevessel disease (odds ratio [OR] 6.3, 0.03). However, as shown in Table 6, rocedural comlications were significantly Table 6. Perirocedural Comlications in 215 Patients (n 117) (n 98) Major comlications Coronary occlusion 5.1% 2.0% 0.30 Emergency CABG 1.7% Sustained VT/VF 0.9% Cardioulmonary arrest 0 0 Free erforation with tamonade 0 0 Stroke 0 0 Death 0 0 Any major comlication 6.8% 2.0% 0.11 Minor comlications Coronary artery sasm 9.4% 1.0% New thrombus formation 4.3% 1.0% 0.10 Distal thromboembolism 0.9% Localized erforation without 1.7% tamonade Any minor comlication 14.0% 2.0% Any rocedural comlication (major or minor) 18.0% 3.1% Data resented are ercent of atients. VT/VF ventricular tachycardia/ ventricular fibrillation; other abbreviations as in Tables 1 and 5.

5 1718 STONE ET AL. JACC Vol. 30, No. 7 LASER ANGIOPLASTY VS. STAND-ALONE ANGIOPLASTY Table 7. Major In-Hosital End Points (includes cardiac catheterization laboratory events) (n 117) (n 98) Death 1.7% 0% 0.50 CABG 2.6% 3.1% 0.83 Emergent 1.7% 0% 0.50 Urgent 0.9% 2.1% 0.59 Elective 0% 1.0% 0.46 MI 4.3% 0% 0.04 Q wave 0.9% 0% 0.65 Non-Q wave 3.4% 0% 0.12 Reeat 7.0% 3.1% 0.19 Any major adverse event* 10.3% 4.1% 0.08 Duration of hosital stay (days) *Death, Q wave or non-q wave myocardial infarction (MI), coronary artery byass graft surgery (CABG) or reeat ercutaneous transluminal coronary angiolasty (). Data resented are mean value SD or ercent of atients. more frequent in atients undergoing laser treatment than stand-alone. By multivariate analysis, the only correlate redictive of rocedural comlications was randomization to laser treatment (OR 7.5, 0.002). In-hosital and late clinical events. Overall clinical success in atients randomized to laser-facilitated was similar to that in atients with stand-alone (89.7% vs. 93.9%, resectively, 0.39). In-hosital adverse events are resented in Table 7, and tended to occur more frequently in the laser-treated grou. Postrocedural MI was more common in laster-treated atients than in those managed with only. Late follow-u was available in 209 (99%) of 212 atients discharged alive at a mean time of months. By actuarial analysis, there was no difference in long-term rates of mortality, MI or reintervention in atients treated with laser versus alone, whether adverse in-hosital events were included (Fig. 1) or excluded (Fig. 2) in the determination. By Cox regression analysis, only the resence of trile-vessel disease was identified as an indeendent correlate of late death, MI or reeat revascularization (OR 2.4, 0.009). Patients with revious MI and thrombus-containing lesions. Because atients randomized to laser treatment had a higher baseline incidence of revious MI and lesions containing thrombus than did atients randomized to only, searate analyses were erformed in these subgrous. When considered indeendently of the randomization arm, revious MI was not a correlate of cumulative 6-month adverse events (death, MI, byass surgery or reeat ) (24.5% in atients with vs. 28.2% in those without a revious MI, 0.90). Similarly, treatment of a thrombus-containing lesion had no effect on the occurrence of cumulative 6-month adverse events (29.0% in atients undergoing treatment of one or more lesions with thrombus vs. 25.7% in atients with no lesions with thrombus, 0.68). Furthermore, no major differences in acute or late outcomes in atients treated with laser versus stand-alone substratified by these baseline differences were identified (Table 8). Discussion Previous studies. Only one rosective, randomized study (16) has been reviously ublished in which the strategy of laque debulking with a laser before was directly comared with stand-alone. In the multicenter Amsterdam Rotterdam (AMRO) trial (16), 308 atients with stable angina and lesions visually 10 mm in length were randomized to excimer laser angiolasty (followed by in 98% of atients) versus only (16). There were no differences in acute or late major clinical events between the two grous. By Figure 1. Kalan-Meier curves dislaying cumulative survival and event-free survival in atients randomized to undergo laserfacilitated (triangles) versus standalone (circles). Outcomes include in-hosital and late events. Inset in each grah are the 6- and 12-month survival rates by actuarial analysis, with the corresonding values by the log rank test. CABG coronary artery byass graft surgery.

6 JACC Vol. 30, No. 7 STONE ET AL. LASER ANGIOPLASTY VS. STAND-ALONE ANGIOPLASTY 1719 Figure 2. Kalan-Meier curves dislaying survival and event-free survival after hosital discharge (excluding in-hosital events) in atients randomized to undergo laserfacilitated (triangles) versus standalone (circles). Format as in Figure 1. CABG coronary artery byass graft surgery. quantitative coronary analysis, similar acute gain was realized after both strategies, but late loss was greater in the lasertreated atients. As a result, restenosis tended to be greater after laser angiolasty than after alone (52% vs. 41%, 0.13). Comared with the ultraviolet excimer laser, the midinfrared holmium laser offers several advantages that warranted a second randomized trial of somewhat different design: 1. The holmium laser may result in less arterial damage than the excimer laser, a contention suorted by registry data (6 9,17). Both the excimer and holmium lasers roduce hotoacoustic trauma by the creation, raid exansion and disersion of vaor gas bubbles that can result in arterial dissection or erforation (18 20). Although the extent of dissection may be reduced by relacing the blood field with saline before excimer treatment (21), a histologic comarative in vitro study (22), in which resently available catheters at clinically relevant energy levels and ulse strategies were used, found that the holmium laser resulted in fewer arterial cleavage lanes (dissections) than did the excimer laser, desite lasting in a saline field. 2. Thrombi, which ossess a high water content, avidly absorb light in the mid-infrared region (23). As a result, the holmium laser has been found to be articularly effective in thrombus-containing lesions and acute ischemic syndromes (7,11,12). In contrast, lower success and greater comlication rates have been reorted after treatment of thrombotic lesions with the excimer laser (24). These observations were incororated into the design of both the AMRO and Angiolasty Versus Angiolasty (LAVA) trials. Whereas the AMRO study excluded atients with unstable angina and thrombuscontaining lesions, the resent trial was secifically weighted to cature these atient subgrous. The solid state design of the mid-infrared laser confers other advantages of this system comared with the excimer, including short warm-u times, minimal maintenance, a smaller footrint, no toxic gases to vent and lower cost (6,23,24). Results of the resent study. Desite these considerations, no acute or late benefits of holmium laser-facilitated versus stand-alone were found in the resent randomized trial, either by univariate or multivariate analysis. success was relatively imroved when treating thrombuscontaining lesions but still did not surass alone. In contrast, rocedural comlications were significantly increased Table 8. Comarison of Outcomes in - and Coronary Angiolasty-Assigned Patients Substratified by Presence of Previous Myocardial Infarction and Lesional Thrombus (n 63) Previous MI No Previous MI 1 Lesion With Thrombus No Lesion With Thrombus (n 35) (n 54) (n 63) (n 32) (n 17) (n 85) (n 81) Procedural success 96.8% 97.1% % 96.8% % 100% % 96.3% 0.95 Clinical success 90.5% 97.1% % 92.1% % 88.2% % 95.1% mo EFS 73.9% 78.8% % 75.3% % 69.3% % 78.0% 0.46 Data resented are ercent of atients. EFS event-free survival (survival free from myocardial infarction [MI], byass surgery or reeat ercutaneous transluminal coronary angiolasty []; includes in-hosital events).

7 1720 STONE ET AL. JACC Vol. 30, No. 7 LASER ANGIOPLASTY VS. STAND-ALONE ANGIOPLASTY by lasing before, esecially the occurrence of sasm, with trends noted for greater abrut coronary occlusion and new thrombus formation. As a result, the rate of erirocedural MI was increased, and trends were resent for greater overall major comlications and a longer hosital stay. Thus, the resent trial does not suort the use of laser angiolasty as an everyday tool, even in high risk atients with unstable angina or thrombus-containing lesions (2,25), esecially when the high costs of the system and single-use catheters are factored into account. The negative results of the LAVA and AMRO trials, in direct contradiction to the earlier favorable registry exeriences, reconfirm the essential imortance of erforming rosective, multicenter, randomized trials before the widesread adotion of new methodologies can be recommended. Limitations of the study. Several limitations of this study must be acknowledged: 1) Given the relatively small samle size, the study was owered to show only major differences between the two treatment arms. Lesser degrees of benefit favoring laser-assisted or stand-alone may have gone undetected. However, given the higher rate of comlications and slightly worse long-term outcomes with lasing in this trial, it is unlikely that enrolling a larger oulation would have revealed significant long-term benefits in the laser arm. 2) Although the two treatment arms were well matched for most baseline characteristics, several differences were resent between the two grous, including the frequency of revious MI and the resence of thrombus-containing lesions. However, when analyzed searately and adjusted for by multivariate analysis, these factors had no bearing on acute or late eventfree survival. 3) Some degree of selection bias cannot be excluded, esecially in investigator reorting of clinical events and angiograhic results. However, the articiating hysicians were dedicated laser investigators, suggesting that bias, if resent, would have been directed toward more favorable laser results. 4) The results of the angiograhic analysis must be cautiously regarded, given the lack of a central core laboratory. However, the lack of any difference in the site-assessed final ercent diameter stenoses between the laser and stand-alone grous suggests that no true angiograhic benefit of laser is likely to exist. Furthermore, the equivalent 6-month clinical outcomes between the two treatment grous are consistent with the nearly identical acute lumen outcomes observed (26). Finally, and erhas most imortantly, the size of the laser catheters used in the resent trial (and the AMRO study), in concert with the observation that laser angiolasty results in minimal laque debulking, may have made the comarative late outcomes after laser-facilitated angiolasty versus standalone a fait accomli. Recent studies have demonstrated that if debulking is to reduce restenosis and imrove late clinical events, it is likely to do so by imroving the acute result obtained (26). However, studies with intravascular ultrasound imaging have shown that with resent-day catheters and techniques, laser debulking of laque contributes only a small ercentage of the lumen gain realized after adjunctive (27). In the resent trial, with a mean catheter size of 1.3 mm used, the average cross-sectional area stenosis after laser alone would be exected to be 81% (assuming 100% ablation efficiency and no significant vessel remodeling). However, given the high rate of rocedural comlications noted with the small diameter catheters utilized in this study, it is doubtful that the use of larger catheters to achieve more comlete laque removal would be safe. The imortant issue of whether maximal laque debulking imroves long-term outcomes after ercutaneous intervention is being addressed with regard to high seed rotational atherectomy in the ongoing Study to Determine Rotablator and Transluminal Angiolasty Strategy (STRATUS) trial. Present role of laser coronary angiolasty. In view of the results of the resent trial, which confirm and extend the AMRO study findings, the routine use of laser angiolasty before is unwarranted. Whether laser facilitation of balloon angiolasty is or is not useful for lesions that are known to resond oorly to, such as ostial lesions, bifurcation stenoses, undilatable lesions and in-stent restenosis (10,28), cannot be answered by these trials because too few atients with these lesion characteristics were included. However, many of these lesion subtyes also resond well to high seed rotational atherectomy, which is otentially a more cost-effective alternative, given the high u-front costs of the laser system. A unique role for lasers in coronary artery disease may yet be found with the laser wire alication to recanalize chronic total occlusions that cannot be traversed by conventional guide wires (29). Aendix Particiating Institutions and Investigators for the Angiolasty Versus Angiolasty Trial Clinical Coordinating Center. The Cardiovascular Institute, El Camino Hosital, Mountain View, California: Gregg W. Stone (Primary Investigator), JoAnn McDonnell, Nancy Richardson. Clinical Centers and Princial Investigators. The University of Miami/ Jackson Memorial Hosital, Miami, Florida: Eduardo de Marchena. Audubon Hosital, Louisville, Kentucky: David Dageforde, Richard Allen. St. Francis Hosital, Evanston, Illinois: Alberto Foschi, Alan Kogan. LDS Hosital, Salt Lake City, Utah: Joseh B. Muhlestein. All Children s Hosital, St. Petersburg, Florida: Michael McIvor. Scottsdale Memorial Hosital, Scottsdale, Arizona: David Rizik. Blodgett Memorial Medical Center, Grand Raids, Michigan: Ronald Vanderlann, Ray Roden. The Cleveland Clinic Foundation, Cleveland, Ohio: Joe Sutton. Eiscoal Heart Institute, Philadelhia, Pennsylvania: Vidya Banka, Peter Fail. Maimonides Medical Center, Brooklyn, New York: Robert Frankel, Jacob Shani. Methodist Hosital, Indianaolis, Indiana: Kirk Parr. Rex Hosital, Raleigh, North Carolina: Daryl Emery. Texas Heart Institute, Houston, Texas: Emerson Perin. University Medical Center, Tucson, Arizona: Samuel Butman. References 1. 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