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J Am Coll Cardiol, 2000; 35:151-156
© 2000 by the American College of Cardiology Foundation
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CLINICAL STUDIES

Effect of plaque debulking and stenting on short- and long-term outcomes after revascularization of chronic total occlusions

Luis Gruberg, MDa,b, Roxana Mehran, MD, FACC, FESCa,b, George Dangas, MD, PhD, FACC, FESCa,b, Mun K. Hong, MD, FACCa,b, Gary S. Mintz, MD, FACCa,b, Ran Kornowski, MDa,b, Alexandra J. Lansky, MDa,b, Kenneth M. Kent, MD, PhD, FACCa,b, Augusto D. Pichard, MD, FACCa,b, Lowell F. Satler, MD, FACCa,b, Gregg W. Stone, MD, FACCa,b and Martin B. Leon, MD, FACCa,b

a Cardiovascular Research Foundation, New York, New York, USA
b Cardiac Catheterization and Intravascular Ultrasound Imaging Laboratories, Washington Hospital Center, Washington, DC, USA. Dr. Gruberg is the recipient of the Physicians Fellowship for Medicine in Israel

Manuscript received February 2, 1999; revised manuscript received May 27, 1999, accepted September 14, 1999.

Reprint requests and correspondence: Dr. Mehran, Director, Clinical Research and Data Coordinating Center, Cardiovascular Research Foundation, 55 E. 59th Street, 6th floor, New York, New York 10022


   Abstract
Top
 Abstract
Methods
 Results
 Discussion
 Conclusions
 References
 
OBJECTIVES

We evaluated the effect of plaque burden modification (debulking) on the short- and long-term clinical outcomes of patients with a totally occluded native coronary artery undergoing successful stent deployment.

BACKGROUND

Although the primary success rate of crossing a chronic totally occluded coronary artery has improved with the development of new interventional devices and guidewires, the rate of acute reocclusion and restenosis remains high.

METHODS

The in-hospital and late clinical outcomes of 150 patients who had undergone successful stenting of 176 chronic total occlusions were analyzed. After successful crossing of the lesion, 44 patients with 50 lesions underwent debulking by laser angioplasty, rotational or directional atherectomy followed by stenting, whereas 106 patients with 126 lesions underwent stent implantation without prior debulking.

RESULTS

Baseline clinical and angiographic characteristics were similar for the two groups, except for a higher incidence of left anterior descending coronary artery location and longer lesions in the group of patients who underwent debulking prior to stenting. In-hospital mortality, myocardial infarction and repeat angioplasty rates were similar for the two groups. At a mean 14 ± 8 months follow-up time, there were no deaths in either group, and target lesion revascularization rates were the same (16.3% in the debulking plus stent group vs. 14.4% in the stent alone group, p = NS).

CONCLUSIONS

Treatment of chronic total native coronary artery occlusions with stent deployment with and without lesion modification (debulking) results in a favorable in-hospital outcome, with relatively low long-term target lesion revascularization rates.

Abbreviations and Acronyms
  CSA = cross-sectional area
  DCA = directional coronary atherectomy
  IVUS = intravascular ultrasound
  LAD = left anterior descending artery
  MI = myocardial infarction
  MLD = minimal lumen diameter
  PTCA = percutaneous transluminal coronary angioplasty
  TIMI = Thrombolysis in Myocardial Infarction
  TLR = target lesion revascularization

Revascularization of chronic total coronary artery occlusions remains an important challenge in interventional cardiology. Although the primary crossing rate has improved with the development of new guidewires (1–4), patients with total occlusions still have an abrupt closure rate up to 8% (5) and a high restenosis rate (50% to 70%) after balloon angioplasty alone (6–11).

These disappointing results can be attributed in part to the increased plaque burden, smaller postprocedural lumen area and larger residual cross-sectional narrowing present after percutaneous transluminal coronary angioplasty (PTCA) of chronic total occlusions compared with nonoccluded vessels (12). These findings suggest that aggressive plaque burden removal may improve clinical outcomes (13,14). In addition, coronary stent implantation after successful recanalization of chronic total occlusion has been shown to reduce restenosis and reocclusion rates and to improve global and regional left ventricular function compared with balloon angioplasty alone (15–19). It is unknown, however, whether plaque reduction (debulking) before stent implantation would further improve late event-free survival.

The purpose of this study was to examine the effect of plaque debulking prior to stenting on the acute and late clinical outcomes of patients undergoing percutaneous revascularization of chronic total occlusions in native coronary arteries.


   Methods
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 Methods
Results
 Discussion
 Conclusions
 References
 
Patient population.   Between July 1996 and July 1997, a total of 150 consecutive patients underwent successful recanalization of 176 totally occluded native coronary arteries (duration of occlusion >2 weeks). These patients represent 73% of the total number of patients with a chronic total occlusion in whom recanalization had been attempted.

Patients were treated with either of two different strategies: 1) lesion modification (debulking) by excimer laser, rotational or directional atherectomy followed by stent deployment in 44 patients (50 lesions), or 2) conventional balloon angioplasty followed by stent placement in 106 patients (126 lesions). Following hospital discharge, patients were either seen at the clinic by the research nurse or contacted by telephone or mail for late clinical follow-up.

Procedure.   Device strategy was selected based on vessel size and anatomy, preprocedural lesion configuration (i.e., lesion eccentricity, ulceration, irregularity, calcification, thrombus or ostial location) and the absence of clinical contraindications at the discretion of the operator. Debulking was achieved with excimer laser, directional coronary atherectomy (DCA) or rotational atherectomy, as previously described (20).

Adjunctive medical therapy.   During the procedure, heparin bolus was administered to achieve an activated clotting time >300 s. Aspirin therapy, 325 mg, was started at least 24 h before the procedure and continued indefinitely. Ticlopidine, 500 mg, was given before the procedure and treatment with it was continued for four weeks (250 mg orally twice daily). Glycoprotein IIb/IIIa inhibitors were used in <2% of the patients in both groups.

Angiographic analysis.   Quantitative angiographic analysis was done at the Angiographic Core Laboratory by an independent observer who was unaware of the purpose or outcome of the study. The analysis was done on end-diastolic cine frames demonstrating the stenosis in its more severe and nonforeshortening projection, using a computer-assisted, automated algorithm (ARTREK, Quantitative Cardiac Systems) and using standard morphologic criteria (21). The contrast-filled catheter was used as the calibration standard. Reference vessel size was assessed from the postprocedural images.

Intravascular ultrasound.   Intracoronary ultrasound (IVUS) studies were performed after intracoronary injection of 200 µg of nitroglycerin with one of the two commercially available systems as previously described (22). In each case, the transducer was advanced approximately 10 mm beyond the lesion and withdrawn automatically at 0.5 mm/s to the aorto-ostial junction. On-line analysis during the procedure was reported to the operator regarding reference vessel diameter, minimal lumen diameter (MLD), stent and lumen cross-sectional area and stent apposition. The images were recorded on a 1/2-in. high-resolution S-VHS tape for off-line analysis and independently reviewed at the IVUS Core Laboratory.

Definitions.   A "total occlusion" was defined as complete interruption of the vessel with Thrombolysis in Myocardial Infarction (TIMI) grade flow 0 (23). "Angiographic success" was defined as recanalization of the artery with a <50% residual diameter stenosis with restoration of TIMI 3 flow. Q-wave myocardial infarction (MI) was defined by the development of new Q waves on the postprocedural ECG. Non-Q-wave MI was defined as the elevation of CPK-MB ≥5 times of normal values without the appearance on new Q waves.

Statistical analysis.   Statistical analysis was performed using software (StatView 4.01; Abacus Concepts; Berkeley, California). Continuous data are presented as mean ±SD. Comparisons between groups were performed using the chi-square test to analyze differences in categorical variables, and the Student t test was used for continuous variables. Follow-up events were analyzed by the Kaplan-Meier method. Freedom from target lesion revascularization (TLR) and for late events was generated for both groups and differences between them compared with the log rank test. Cox proportional hazards regression analysis was performed to determine the independent correlates of TLR and late events. Clinical, morphologic and procedural variables were entered into a multiple logistic regression model to determine the following independent correlates of TLR and event-free survival: age, gender, history of diabetes, lesion length, ostial location, left anterior descending coronary artery, restenotic lesion, preprocedural reference vessel diameter, final MLD and final cross-sectional area (CSA). The level of significance was p < 0.05.


   Results
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Discussion
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Patient characteristics.   The baseline clinical characteristics for all 150 patients with 176 totally occluded native coronary lesions who had undergone either one of the two treatment strategies are shown in Table 1. Mean age was 59 ± 12 years (range, 30 to 88 years), and 113 (75.8%) were male. The group undergoing debulking before stenting included more male patients, with a higher, but not significant, number of diabetic patients and patients who had undergone aortocoronary bypass surgery. Accelerated angina was present in 66.7% of patients who had undergone stenting and in 68.2% of patients who had undergone debulking prior to stenting (p = NS), whereas recurrent angina after an MI was present in 15.7% and 11.4%, respectively (p = NS).


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  		Table 1 Baseline Characteristics*

 
Revascularization strategies.   Debulking was performed prior to stenting in 44 patients with 50 lesions. Excimer laser was used in 34 lesions (68%), rotational atherectomy in 10 lesions (19%) and directional atherectomy in 6 lesions (13%). Stent alone was used in 106 patients with 126 lesions. A single stent was deployed in 47 patients (31%), 2 stents in 56 patients (37%) and >3 stents in 47 patients (31%). An average of 2.03 ± 1.06 stents were used in each patient.

Angiographic and IVUS characteristics.   Intravascular ultrasound was performed in 86.1% of the lesions after successful recanalization of the artery and at the end of the procedure. The angiographic and IVUS characteristics for these lesions are detailed in Table 2. The left anterior descending artery (LAD) was the target vessel in 50% of the patients who had undergone debulking with stent deployment, compared with 21% in the other group (p = 0.001). These patients also had longer lesions than the patients who had undergone stenting alone (10.4 ± 6.5 mm vs. 23.0 ± 14.1 mm, p = 0.03). Postrecanalization, prestenting reference vessel diameter, preprocedural lesion CSA, final lumen CSA and final MLD were slightly larger in patients who had undergone stenting alone, although the differences were not statistically significant (Table 2).


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  		Table 2 Angiographic and Intravascular Ultrasound Lesion Characteristics*

 
In-hospital events.   Clinical events during hospitalization are presented in Table 3. Death, Q-wave and non Q-wave MI rates did not differ significantly between the two groups. Major vascular complications requiring surgical repair or blood transfusion were also similar between the groups.


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  		Table 3 In-Hospital Clinical Outcome*

 
Clinical follow-up.   Data were available for 98% of the patients, at mean follow-up time of 14 ± 8 months (Table 4). There were no deaths during this period in either of the two groups. There was a higher incidence of Q-wave MI in the debulking plus stent group compared with the stent alone group (7% vs. 0%, p = 0.02). The incidence of TLR was similar for both groups respectively (16.4% vs. 14.4%, p = NS). By Cox regression analysis, age was identified as the only independent predictor of TLR (odds ratio: 0.958; confidence interval, 0.93 to 0.98, p = 0.0008).


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  		Table 4 Long-term Outcome*

 

   Discussion
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 Abstract
 Methods
 Results
 Discussion
Conclusions
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Despite improvements in the rate of recanalization of chronic total occlusions, there is still a 7% to 8% risk of acute reocclusion (5,18) and a 50% to 70% rate of six-month restenosis after balloon angioplasty (5–11,24–27). These suboptimal results can be attributed to the increased plaque burden, a smaller postprocedural lumen area and a larger residual percentage of cross-sectional narrowing present in chronic total occlusions compared with nonoccluded vessels after angioplasty (12).

Early reports suggested that stenting of chronic total occlusions might reduce the rates of early reocclusion and restenosis (12,15,16,28). These data have been confirmed by recently published randomized, controlled trials (16–19). However, restenosis rates are still high after stenting of chronic total occlusions with reported rates of 22% to 32% (16–18). Plaque debulking prior to stenting may render additional benefits by removing the increased plaque burden seen in this type of lesion and also allow for the successful treatment of lesions that would be inadequately treated with stent alone. However, to our knowledge, the outcome of debulking prior to stenting in chronic total occlusions has not been studied previously.

The present study analyzed the in-hospital and long-term outcome of all patients in our institution who had undergone successful recanalization of chronic totally occluded native coronary arteries over a one-year period and were treated either by debulking plus stent or by stenting alone. Both groups of patients had similar baseline clinical and angiographic characteristics, except for a higher incidence of male patients with longer lesions located more frequently in the LAD distribution in the group of patients who had undergone debulking prior to stenting. Reference vessel size and final lumen dimensions were similar between the groups. This is important in light of previous studies that showed that the benefit from stenting after PTCA of a chronic total occlusion is derived from the larger final lumen achieved with this strategy when compared with PTCA alone (19). Importantly, in-hospital outcomes were similar between both groups with low death rates (<1%), Q-wave MI (<3%), repeat PTCA (5% to 7%) and major vascular complications (7%). Although the incidence of CPK-MB elevation ≥5 x normal was frequent in both groups (13.6% vs. 19.6%, p = NS), there was no increase in either short-term or long-term mortality in either one of the groups.

In the present study, the debulking devices included 68% excimer laser and 19% rotational atherectomy. We do not believe there is a significant difference in restenosis rates among the various ablation devices in the studied setting. In the recently published results of the ERBAC trial, excimer laser angioplasty and rotational atherectomy had similar clinical outcomes and restenosis rates for the treatment of complex coronary lesions (29).

During long-term follow-up, there was no difference in death (0%) or TLR rates (14.4% vs. 16.3%, p = NS) between the two groups. There was a higher incidence of late Q-wave MI in the group of patients who had undergone debulking and stent deployment.

Thus, debulking plus stent deployment achieved similar TLR rates when compared with stent alone, despite the higher frequency of longer lesions and LAD location, characteristics that have been associated with an increased incidence of in-stent restenosis (30–32). These results may convey the appropriate selection of a debulking strategy after successful recanalization of such lesions. However, neither one of these factors nor debulking prior to stenting was an independent predictor of TLR or decreased event-free survival when analyzed in a statistical model; age was the sole independent predictor of TLR.

Study limitations.   The present study was a retrospective analysis, and therefore the conclusions and results are subject to the limitations inherent in all such reports. Operator evaluation of each individual case, the selection of debulking before stent deployment and the specific device used may be important limitations. Patients did not undergo routine follow-up catheterization to assess the angiographic restenosis rate and early reocclusion rate, which has been shown to be high and may be clinically silent because of preexisting collateral flow (19). However, we found an encouraging relatively low rate of clinical restenosis for a population of patients in whom results have been discouraging in the past with balloon angioplasty alone (31,32). Application of a debulking strategy was implemented without a protocol to dictate a specific reduction in plaque burden. Thus, we did not necessarily evaluate "optimal" (or "maximal") debulking in this study. It is unknown whether debulking with high ablation efficiency in this type of lesions might yield even better results. Finally, the small study population may not allow for appropriate correction of baseline imbalances between the groups. This may have introduced a bias against the debulking plus stent approach, as this group included longer and more LAD lesions.


   Conclusions
Top
 Abstract
 Methods
 Results
 Discussion
 Conclusions
References
 
Treatment of chronic total native coronary artery occlusions with stent deployment with or without debulking results in favorable short- and long-term clinical outcomes. The TLR rates were similar in the two strategies, indicating the success of plaque burden reduction prior to stenting in longer and LAD lesions. A prospective randomized study should evaluate more aggressive "optimal" debulking prior to stenting for the treatment of totally occluded native coronary arteries.


   References
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