- Email: [email protected]
Short- and long-term outcomes of Wiktor stent implantation at low versus high pressures
Short- and Long-Term Outcomes of Wiktor Stent Implantation at Low Versus High Pressures Paul Yang, MD, Mariann Gyongyosi, MD, PhD, Ali Hassan, MD, Gu¨nter Heyer, MD, Werner Klein, MD, Olev Luha, MD, Edwin Maurer, MD, Volker Mu¨hlberger, MD, Othmar Pachinger, MD, Heinz Sochor, MD, Josef Sykora, MD, Heinrich Weber, MD, Franz Weidinger, MD, and Dietmar Glogar, MD, on behalf of the Austrian Wiktor Stent Study Group A prospective, randomized, multicenter trial was conducted to evaluate whether high-pressure postdilation of the Wiktor stent provides short- and long-term benefits compared with the conventional low-pressure implantation technique. From June 1995 through May 1996, 181 patients were randomly assigned to either low-pressure (6 to 12 atm, group A, n ⴝ 94) Wiktor stent placement or to high-pressure postdilation (>13 atm, group B, n ⴝ 87) after stent deployment. All patients were followed up clinically for 7 ⴞ 3 months, with an angiographic follow-up in 154 patients (85%). After stent implantation, neither minimal lumen diameter (MLD) nor percent diameter stenosis (%DS) differed significantly between the 2 groups (MLD, 2.8 ⴞ 0.5 vs 2.9 ⴞ 0.5 mm; %DS, 17 ⴞ 8% vs 16 ⴞ 9% for groups A and B, respectively). However, a trend toward a larger mean lumen diameter within the stent was observed in group B (3.3 ⴞ 0.6 vs 3.5 ⴞ 0.5 mm for
groups A and B, respectively; difference between means 0.14 mm, 95% confidence interval ⴚ0.01 to 0.29, p ⴝ 0.08). Angiographic follow-up revealed similar MLD and %DS in both treatment groups (MLD, 2.1 ⴞ 0.7 vs 2.2 ⴞ 0.8 mm; %DS, 31 ⴞ 17% vs 30 ⴞ 24% for groups A and B, respectively, p ⴝ NS). Acute stent thrombosis occurred in 2 patients (1%) (1 patient in each group), and subacute thrombosis in 1 patient (0.6%) in group A. There was 1 death in group A, and target lesion restenosis (>50% DS) was observed in 15% of patients with no differences between the groups. In conclusion, this study demonstrated favorable short- and long-term results of Wiktor stent implantation. Despite a trend toward additional initial lumen gain by high-pressure postdilation, this did not translate into a measurable improvement in long-term outcome. 䊚1999 by Excerpta Medica, Inc. (Am J Cardiol 1999;84:644 – 649)
n contrast to numerous stainless steel stents of tubular or mesh design, there are insufficient data Iregarding adjunctive high-pressure balloon dilation in
trial (the Austrian Wiktor Stent Trial) was therefore designed to evaluate whether high-pressure postdilation of the Wiktor stent provides short- and long-term benefits compared with the conventional low-pressure approach.
1– 6
coil stents, such as Wiktor stents. The Wiktor stent, a single-wire tantalum coil stent, has not undergone profound prospective investigations with respect to safety and efficacy of high-pressure stenting. It is conceivable that the coil configuration (in conjunction with other factors, such as different stent composition other than stainless steel) may allow optimal stent deployment without the need for adjunctive highpressure balloon dilation. Furthermore, whether aggressive balloon dilation increases the amount of reactive intimal proliferation and thus leads to even more late lumen loss and higher restenosis needs to be clarified.7–9 This prospective, randomized, multicenter From the Department of Cardiology, University Clinic of Internal Medicine II, Vienna; Second Department of Internal Medicine, Landeskrankenanstalten Salzburg, Salzburg; Department of Internal Medicine, Karl-Franzens-University, Graz; Department of Cardiology, Medical Hospital Wels, Wels; Department of Internal Medicine, University Hospital of Innsbruck, Innsbruck; Second Medical Department, Landeskrankenhaus Klagenfurt, Klagenfurt; and Fifth Department of Internal Medicine, Kaiser-Franz-Josef-Hospital, Vienna, Austria. This study was supported by an educational grant from Medtronic Austria, Vienna, Austria. Manuscript received November 16, 1998; revised manuscript received and accepted May 5, 1999. Address for reprints: Dietmar Glogar, MD, Department of Cardiology, University Clinic of Internal Medicine II, Waehringer Guertel 18-20, A-1090 Vienna, Austria. E-mail: [email protected].
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©1999 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 84 September 15, 1999
METHODS
Study population and protocol: From June 1995 through May 1996, a total of 202 patients were enrolled prospectively in the trial, which was conducted in 7 Austrian centers. All patients had objective evidence of myocardial ischemia and angiographic evidence of a target lesion suitable for stent implantation. Indications for stent implantation included elective (primary) stenting, ⱖ50% stenosis after balloon angioplasty, and threatening or acute vessel closure after balloon dilatation. Exclusion criteria included a reference diameter ⬍2.5 mm by visual estimation, vessels with poor or compromised runoff distal to the target lesion, heavily calcified lesions that would preclude adequate predilatation, and evidence of intracoronary thrombus. Patients with contraindications or intolerance to therapy with aspirin or ticlopidine were also excluded. Patients were randomly assigned by means of cards in sealed envelopes to either low-pressure Wiktor stent placement at low pressures (6 to 12 atm, group A) or to high-pressure postdilation (ⱖ13 atm, group B) after stent deployment at low pressures. A cross0002-9149/99/$–see front matter PII S0002-9149(99)00409-9
over between randomization groups was possible at the operator’s discretion when this was deemed necessary. The investigational protocol was approved by the local ethical committees of each participating center and written informed consent was obtained from all patients. Stent implantation procedure: Coronary angiography and stent implantation procedures were performed according to standard clinical practice in each participating center, by a femoral approach using a 7Fr or 8Fr guiding catheter. All patients were pretreated with aspirin (ⱖ100 mg/day). Pretreatment with ticlopidine (ⱖ250 mg/day) was started on the day of the procedure. In patients scheduled for elective stent implantation, ticlopidine was given beginning 1 or 2 days before the scheduled procedure. During coronary intervention, patients received an intravenous bolus of 10,000 to 15,000 IU of heparin to maintain an activated clotting time of ⬎300 seconds. The Wiktor stent (Medtronic, Kerkrade, The Netherlands) used during this trial is a balloon-expandable stent of helical coil design composed of a single strand of tantalum wire 0.005 inches in diameter and shaped in a sinusoidal wave pattern. The stent is premounted on a semicompliant polyethylene balloon catheter. Two different stent delivery systems were used at the operator’s discretion: a “Gold-X” single-operator-exchange delivery system with a 16-mm Wiktor stent premounted (used in 88% of patients), or a “Prime” over-the-wire system with a 15-mm Wiktor stent (used in 12%). Nominal, low pressures of 6 to 8 atm were used to expand the stent. In group A, investigators were permitted to use further balloon inflations at low pressures (⬍12 atm) after stent insertion when necessary. In patients assigned to group B, however, a further high-pressure balloon inflation (ⱖ13 atm) was required after stent deployment regardless of the initial stent result. Postprocedure medical regimen: There was no strict postprocedure medication protocol to be used during the trial. However, a recommendation was given before the trial: aspirin ⱖ100 mg/day for 6 months and ticlodipine ⱖ250 mg/day for 4 weeks. There were only minor differences in the dose of the antiplatelet regimen used in the participating institutions: Aspirin 100 mg once daily and ticlopidine 250 mg twice daily were given in 4 of the 7 participating centers (60% of the study patients); aspirin 250 mg once daily and ticlopidine 250 mg twice daily in 2 centers (20%); and aspirin and ticlopidine both 250 mg once daily were given in 1 center (20%). Data collection: All demographic, clinical, and procedural data were recorded prospectively on standardized patient case report forms and forwarded to the core laboratory at the Vienna University Hospital Cardiac Catheterization Laboratories. Each investigating institution was visited by study monitors at regular intervals for data collection and to ensure the quality of clinical and angiographic follow-up data. Evidence of target lesion calcifications or dissections and lesion types (classified according to a simplified American
College of Cardiology/American Heart Association score)10 were determined by each operator and indicated on the case report forms. Quantitative angiographic analysis: Quantitative coronary angiographic (QCA) analysis of all procedural and follow-up cineangiograms were performed at the core laboratory with the use of a validated edge-detection program (Cardiovascular Measurement System Version 2.3D, Medis Medical Imaging Systems, Nuenen, The Netherlands), which has undergone extensive validation studies and has been described in detail elsewhere.11,12 Minimal lumen diameter (MLD), reference diameter (by interpolation), percent diameter stenosis, and mean lumen diameter were measured. In stented vessel segments, MLD was repositioned manually within the stent, when it was initially detected outside the stented segment. Calibration was performed in each analyzed cineangiographic frame on contrast-filled catheters as a scaling device to determine the absolute value (in mm) of MLD. All QCA measurements were obtained in identical views at baseline, after stent implantation, and at follow-up, after maximal vasodilation with 0.1 to 0.3 of mg of intracoronary nitroglycerin. End-diastolic frames were selected for analysis from multiple, preferably orthogonal, views that best showed the target lesion with no significant foreshortening and overlapping structures. Mean values were calculated from multiple matched views for all quantitative angiographic variables. Stenoses present at follow-up and located at the proximal or distal outflow of the stent were not measured by means of QCA, but classified as “peri-stent restenosis” and indicated as such on patient case report forms by each operator when a ⱖ50% diameter stenosis was evident by visual inspection. Acute lumen gain was defined as the net difference between the pre- and postintervention MLD, and late lumen loss was defined as the net difference in MLD between the postintervention result and the follow-up angiogram. The ratio of late loss to acute gain was reported as the loss index. Intravascular ultrasonic analysis: Intravascular ultrasound (IVUS) imaging was performed as an optional part of the study protocol in a subset of the patient cohort (n ⫽ 31) after diagnostic coronary angiography and stent implantation. IVUS images were obtained with either mechanical (2.9 or 3.2 F, CVIS, Sunnyvale, California) or phased-array electronic IVUS catheters (3.0 F, EndoSonics, Rancho Cordova, California) after intracoronary administration of 0.1 to 0.2 mg of nitroglycerin and stored on s-VHS videotapes for subsequent off-line analysis. Minimal lumen cross-sectional areas were measured in the narrowest segment within the lesion or stent. Lumen cross-sectional areas from segments proximal and distal to the target lesion or stent were averaged and used as reference values. Absolute values of minimal lesion or stent cross-sectional areas were also expressed as percentages of the reference cross-sectional area. Study end points and statistics: The primary study end point was the angiographic MLD at follow-up. The sample size of 74 patients in each group with
CORONARY ARTERY DISEASE/LOW– VS HIGH–PRESSURE WIKTOR STENT IMPLANTATION
645
angiographic follow-up was determined at the outset of the study to detect a 0.3-mm difference in MLD between the 2 randomized groups, with an assumed standard deviation of 0.65 mm, an ␣ error of 0.05, and 80% power. Secondary study end points were: (1) angiographic target lesion restenosis (ⱖ50% diameter stenosis in the stented segment by core laboratory QCA analysis at follow-up); and (2) occurrence of any 1 of the following major adverse cardiac events: death (considered to be cardiac in absence of clear evidence of noncardiac origin), nonfatal myocardial infarction (serum creatine phosphokinase levels twice the upper limit of normal with MB fraction ⱖ6%, and/or development of new pathologic Q waves on the electrocardiogram), lesion-related coronary artery bypass surgery, and target lesion reintervention. For patients experiencing ⬎1 event, the first event reached was considered. All statistical analyses were performed on a pertreatment (as-treated) basis according to the final treatment in order to take into account crossovers from the initial randomization. Continuous variables are expressed as mean ⫾ SD and were analyzed by 2-tailed t tests. To avoid possible errors produced by unequal variances of the means in the 2 groups, the Welch modified t test was applied when necessary, which yielded similar results. The means of QCA and IVUS measurements after stent implantation and at follow-up were compared by the paired t test. This test was also used to compare the means before and after high-pressure postdilation within the patients in group B. The 95% confidence intervals (CI) were calculated.13,14 The Kolmogorov-Smirnov test was applied to compare the 2 groups for distribution of MLD at baseline, after stent implantation, and at follow-up. Categoric variables are reported as percentages and were analyzed by the chi-square test or by Fisher exact tests when necessary. A statistical probability ⬍0.05 was considered to indicate significance. All statistical analyses were performed using a commercially available software package (S-Plus release 3.4, MathSoft, Cambridge, Massachusetts).
RESULTS
Baseline characteristcs: From 202 patients initially
enrolled in the trial, a total of 181 patients were finally included in the trial and eligible for analysis. Seventeen patients were excluded from final analysis; due to protocol violation in 9, withdrawal of the informed consent in 8, and stent delivery failure in 4. Baseline clinical and angiographic characteristics of the study patients are summarized in Tables I and II. Of the 181 patients, 94 (52%) were randomly assigned to group A and 87 (48%) to group B. There were no statistical differences between groups A and B for all baseline clinical and angiographic variables analyzed. Immediate results: A total of 200 stents were placed in 181 patients (1.1 stent/patient). The balloon:artery ratio (ratio of maximal balloon diameter and reference vessel diameter as determined by QCA analysis) was similar in both groups (1.1 ⫾ 0.2 in group A and 1.1 ⫾ 0.2 in group B; p ⫽ NS). Mean maximal balloon 646 THE AMERICAN JOURNAL OF CARDIOLOGY姞
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TABLE I Baseline Clinical Characteristics of Study Patients Group A Group B All Patients (n ⫽ 94) (n ⫽ 87) (n ⫽ 181) No. of randomized Age (yr) Male gender Ejection fraction (%) Diabetes mellitus Hypertension Hypercholesterolemia Smoking Recent myocardial infarction Stable angina Unstable angina 1-vessel disease 2-vessel disease 3-vessel disease Indications for stent Elective Suboptimal angioplasty result Bailout
61 69 60 20 47 47 35 16 54 40 44 39 11
94 ⫾ 10 (73%) ⫾ 14 (21%) (50%) (50%) (37%) (17%) (57%) (43%) (47%) (41%) (12%)
59 70 60 14 39 50 42 11 45 42 53 28 6
87 181 ⫾ 11 60 ⫾ 11 (80%) 139 (77%) ⫾ 14 60 ⫾ 14 (16%) 34 (19%) (45%) 86 (48%) (57%) 97 (54%) (48%) 77 (43%) (13%) 27 (15%) (52%) 99 (55%) (48%) 82 (45%) (61%) 97 (54%) (32%) 67 (37%) (7%) 17 (9%)
30 (32%) 30 (34%) 60 (33%) 57 (61%) 55 (63%) 112 (62%) 7 (7%) 2 (3%) 9 (5%)
TABLE II Baseline Angiographic Characteristics of Study Patients
Coronary artery size (mm) Minimal lumen diameter before procedure (mm) Diameter stenosis (%) Coronary artery stented Left anterior descending Left circumflex Right Saphenous vein graft Target lesion De novo Restenotic Calcium Dissection Lesion type A B C
Group A (n ⫽ 94)
Group B (n ⫽ 87)
All Lesions (n ⫽ 181)
3.0 ⫾ 0.6 1.1 ⫾ 0.5
3.1 ⫾ 0.6 1.2 ⫾ 0.5
3.1 ⫾ 0.6 1.1 ⫾ 0.5
62 ⫾ 15
64 ⫾ 16
63 ⫾ 16
34 (36%) 16 (17%) 44 (47%) 0
23 18 43 3
(26%) (21%) (50%) (3%)
57 34 87 3
(31%) (19%) (48%) (2%)
73 21 33 48
69 18 32 27
(77%) (23%) (37%) (31%)
142 39 65 75
(78%) (22%) (36%) (41%)
(78%) (22%) (25%) (51%)
32 (34%) 51 (54%) 11 (12%)
30 (34%) 40 (46%) 17 (20%)
62 (34%) 91 (50%) 28 (15%)
inflation pressures were 8.9 ⫾ 2.7 atm in group A and 14.6 ⫾ 1.4 atm in group B (p ⬍0.001). A crossover between treatment groups occurred in 7 patients in group A and in 6 patients in group B. Reasons for the crossover from group A to B were insufficient stent results despite postdilations with low pressures requiring further balloon inflations at high pressures. In 6 patients initally randomized to group B, high-pressure postdilation was not performed because of a potential procedural risk of recrossing the stented lesion with a further balloon for high-pressure postdilation. In 2 patients in group B, the balloon burst after Wiktor stent implantation at high pressure, which was not observed in patients in group A. The early (acute and subacute) clinical outcome is shown in Table III. Acute stent thrombosis occurred in 1 patient in group A and in 1 patient in group B. These patients had a nonfatal Q-wave myocardial infarction and underwent repeat angioplasty. One patient in group A SEPTEMBER 15, 1999
TABLE III Early Clinical Outcome Group A Group B All Patients (n ⫽ 94) (n ⫽ 87) (n ⫽ 181) Acute stent thrombosis Subacute stent thrombosis Major adverse cardiac events Death Acute myocardial infarction Coronary bypass surgery Repeat coronary angioplasty
1 (1%) 1 (1%) 2 (2%) 0 2 (2%) 0 0
1 (1%) 0 1 (1%) 0 1 (1%) 0 0
2 (1%) 1 (1%) 3 (2%) 0 3 (2%) 0 0
experienced a nonfatal Q-wave myocardial infarction due to subacute stent thrombosis and was subsequently referred to coronary artery bypass surgery. The QCA results are summarized in Table IV. No significant differences were found between groups A and B for all final QCA measurements after the procedure. A trend toward a larger mean lumen diameter within the stent was found for group B (p ⫽ 0.08). In group B, the MLD increased from 1.2 ⫾ 0.5 mm at baseline to 2.7 ⫾ 0.6 mm immediately after stent insertion at low pressures (p ⬍0.01), which was slightly but not significantly lower than the MLD in group A. After high-pressure postdilatation there was a further increase in MLD to 2.9 ⫾ 0.5 mm (difference between means, 0.24 mm, 95% CI 0.16 to 0.32, p ⬍0.05). The cumulative frequency distributions of MLD for groups A and B are depicted in Figure 1. The distribution curves were essentially identical for both groups at baseline. After stent implantation, however, a significant larger MLD was found in group B for distribution ranges below the 30% quartile. (p ⫽ 0.0116). In 31 patients (17% of total study cohort; 14 and 17 patients in groups A and B, respectively), IVUS examination was performed after diagnostic coronary angiography and stent implantation. There were no differences in baseline lumen cross-sectional areas between groups A and B (4.6 ⫾ 1.9 and 4.3 ⫾ 1.4 mm2 for groups A and B, respectively; difference between means, 0.36 mm2, 95% CI ⫺1.56 to 0.84). After stent implantation, the final lumen cross-sectional area, expressed both as an absolute value and as a percentage of the reference cross-sectional area, was slightly larger in group B. These differences, however, were not significant: 6.7 ⫾ 1.4 mm2 (70 ⫾ 24%) in group A versus 7.4 ⫾ 1.5 mm2 (79 ⫾ 11%) in group B, difference between means 0.72 mm2 (9.4%), 95% CI ⫺0.34 to 1.78 mm2 (⫺3.9% to 22.7%). Similar to the findings from the QCA analysis, comparison of the cross-sectional areas before and after high-pressure postdilation within group B revealed a significant larger lumen cross-sectional area after high-pressure postdilation. The lumen cross-sectional area had increased from 6.1 ⫾ 1.2 mm2 before to 7.4 ⫾ 1.5 mm2 after high-pressure postdilation (difference between means 1.28 mm2, 95% CI 1.09 to 1.47, p ⫽ 0.048),
and when expressed as a percentage of the reference, from 68 ⫾ 8% to 79 ⫾ 11% (difference between means 11%, 95% CI 9.2 to 12.8, p ⫽ 0.019). Long-term results: Long-term clinical follow-up was achieved in all eligible patients, and follow-up angiography was performed in 154 patients (85%; 76 and 78 patients in groups A and B, respectively) at an interval of 7 ⫾ 3 months after Wiktor stent implantation for both groups. Angiographic and clinical follow-up results are listed in Tables IV and V. The follow-up QCA analysis revealed an MLD of 2.1 ⫾ 0.8 mm and a percent diameter stenosis of 31 ⫾ 21% for the total study population, with no significant differences between the 2 groups. In addition, the cumulative distribution curves of MLD, which was shifted to the right in group B immediately after stent implantation, renarrowed at follow-up, thus revealing no between-group difference (Figure 1). Late lumen loss, loss index, and net lumen gain were not significantly different between groups A and B. Target lesion restenosis, as previously described, was present in a total of 28 patients (14 patients in each group, 15%). There was 1 sudden death in group A at 1 month after stent implantation. No coronary bypass surgery and no acute myocardial infarctions were recorded in either group during the follow-up period. Repeat angioplasty of the stented vessel segment was performed in 13 and 12 patients (both 14%) in groups A and B, respectively, driven by clinical signs of ischemia and/or angiographic evidence of restenosis as assessed visually by each operator-investigator. The overall incidence of major adverse cardiac events at follow-up was 14%, with no difference between the 2 groups (Table V).
DISCUSSION The present study is the first to investigate in a prospective, randomized fashion the short- and longterm benefit of high-pressure implantation of a singlewire coil stent compared with the conventional lowpressure approach. Our results demonstrate favorable clinical and angiographic outcomes with the Wiktor stent, revealing a low incidence of adverse events and target lesion restenosis, with no differrences between the low- and high-pressure randomized groups. Immediate clinical and angiographic results: The incidence of acute or subacute stent thrombosis (2%), with no difference between groups, in the present trial was comparable to results from other tubular or coil stents15,16 and remarkably lower than those observed in previous published studies of the Wiktor stent for bailout procedures or restenotic lesions.17,18 This may be attributed to refinements and improvements over the past few years in poststent medical treatment, and procedural technique and equipment in addition to other factors such as multiple stenting, different stent indications, or patient profile. Recent observations suggest that a more complete stent expansion with the use of high-pressure balloons should lead to improved strut/vessel contact even without IVUS guidance.2,3 This technique seems to
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TABLE IV Quantitative Angiographic Results Group A (n ⫽ 94) Minimal lumen diameter (mm) Baseline After stent implantation Follow-up* Mean lumen diameter (mm) Baseline After stent implantation Follow-up Reference diameter (mm) Baseline After stent implantation Follow-up Percent diameter stenosis (%) Baseline After stent implantation Follow-up Acute lumen gain (mm) Late lumen loss (mm) Net lumen gain (mm) Loss index
Group B (n ⫽ 87)
Difference Between Groups (mean [95% CI])
All Lesions (n ⫽ 181)
1.1 ⫾ 0.5 2.8 ⫾ 0.5 2.1 ⫾ 0.7
1.2 ⫾ 0.5 2.9 ⫾ 0.5 2.2 ⫾ 0.8
0.01 [⫺0.14 to 0.16] 0.11 [⫺0.03 to 0.25] 0.05 [⫺0.18 to 0.28]
1.1 ⫾ 0.5 2.9 ⫾ 0.5 2.1 ⫾ 0.8
1.9 ⫾ 0.5 3.3 ⫾ 0.6 2.7 ⫾ 0.7
2.02 ⫾ 0.5 3.5 ⫾ 0.5 2.8 ⫾ 0.7
0.10 [⫺0.05 to 0.25] 0.14 [⫺0.01 to 0.29] 0.03 [⫺0.17 to 0.23]
2.0 ⫾ 0.5 3.4 ⫾ 0.5 2.8 ⫾ 0.7
3.0 ⫾ 0.6 3.4 ⫾ 0.6 3.0 ⫾ 0.7
3.1 ⫾ 0.6 3.5 ⫾ 0.5 3.1 ⫾ 0.6
0.06 [⫺0.11 to 0.23] 0.10 [⫺0.06 to 0.26] 0.04 [⫺0.16 to 0.24]
3.1 ⫾ 0.6 3.4 ⫾ 0.5 3.1 ⫾ 0.7
0.7 ⫺0.8 ⫺0.7 0.10 0.07 0.05 0.02
63 17 31 1.7 0.7 1.0 0.4
62 17 31 1.7 0.7 1.0 0.4
⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾
15 8 17 0.6 0.6 0.7 0.4
63 16 30 1.8 0.8 1.0 0.4
⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾
16 9 24 0.5 0.8 0.8 0.4
[⫺3.9 to 5.3] [⫺3.3 to 1.7] [⫺6.8 to 5.4] [⫺0.07 to 0.27] [⫺0.14 to 0.28] [⫺0.18 to 0.28] [⫺0.10 to 0.14]
⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾
16 8 21 0.6 0.7 0.7 0.5
*Number of patients with angiographic follow-up was 76 (81%) in group A, 78 (90%) in group B, and 154 (85%) in total.
certain benefit of high-pressure postdilatation on immediate outcome can be demonstrated by analysis of the frequency distribution functions for MLD (Figure 1), which illustrates an improvement in the immediate angiographic result by high-pressure application in patients with a relatively small postintervention MLD (⬍2.7 mm). Furthermore, MLDs and areas, as measured by QCA and IVUS, respectively, were slightly smaller in the high-pressure group immediately after stent insertion at low pressures, but improved significantly after high-pressure postdilatation. Long-term outcome: Several investigators have highlighted a potential drawback of high-pressure stenting based on concerns that high-pressure balloon inflation may increase vessel wall injury and reactive neointimal formation, eventually FIGURE 1. Cumulative frequency distribution of MLD at baseline (Pre), after stent leading to a higher late lumen loss.7–9,19 implantation (Post), and at follow-up (Fup) for groups A and B. There was no A recently published unicenter retrospecdifference in baseline distribution between the 2 groups, but after stent implantation, the curve for group B is shifted to the right, particularly in ranges below tive analysis comparing “aggressive” the 30% quartile (p ⴝ 0.0116). At 6-month follow-up, the difference narstent deployment techniques using overrowed below the significance level. sized balloons (⬎1.15 balloon/artery ratio) or high-inflation pressures (ⱖ12 atm) with “nonaggressive” stent implantation confer a greatly reduced rate of stent thrombosis, which strategies has revealed no increase in late lumen loss may eliminate the need for systemic anticoagulation and or restenosis after aggressive stent implantation.20 its complications. We have found that the final lumen Consistent with this finding, our results show no sigdimensions as measured by both QCA and IVUS did not nificant differences in late outcome between the 2 differ significantly between the high- and low-pressure randomized groups. No statistical differences in folgroups immediately after stent implantation. Although a low-up MLD could be detected between the low- and trend toward a greater lumen gain could be observed for high-pressure groups at follow-up, not only with refinal MLD and mean lumen diameter in the high-pres- spect to absolute diameters or percent diameter stenosure group than in the low-pressure group, neither sis, but also with regard to the frequency distribution reached the level of statistical significance. However, a of the follow-up MLD (Figure 1). The overall target 648 THE AMERICAN JOURNAL OF CARDIOLOGY姞
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TABLE V Occurrence of Adverse Cardiac Events and Angiographic Restenosis
Follow-up (mo after procedure)* Target lesion restenosis In-stent restenosis Peristent restenosis Major adverse cardiac events Death Acute myocardial infarction Target lesion revascularization
Group A (n ⫽ 94)
Group B (n ⫽ 87)
All Patients (n ⫽ 181)
7⫾3
7⫾3
7⫾3
14 11 3 14
(15%) (12%) (3%) (15%)
14 9 5 12
(16%) (10%) (6%) (14%)
1 (1%) 0
0 0
13 (14%)
12 (14%)
28 20 8 26
(15%) (11%) (4%) (14%)
1 (0.6%) 0 25 (14%)
*Clinical follow-up was achieved in 100% of eligible patients and angiographic follow-up was available in 76 patients (81%) in group A, 78 (90%) in group B, and 154 (85%) in total.
lesion restenosis and reintervention rates (15% and 14%, respectively) in our study compare favorably with those reported in previous follow-up studies of Wiktor stents.17,18,21 A similar restenosis rate was found in a recently published multicenter study of the Wiktor stent in chronic total coronary occlusions, when patients with multiple stents (45% of total study population) were disregarded.22 This finding, in conjunction with the encouraging follow-up results of the present trial, may testify to the long-term effectiveness of Wiktor stent implantation even in non–“Benestentlike” lesions. Acknowledgment: We are grateful to Klaus Felsenstein, PhD, Institute of Statistics, Technical University of Vienna, Austria, for statistical advise and critical review of the manuscript.
1. Colombo A, Hall P, Nakamura S, Almagor Y, Maiello L, Martini G, Ganglione A, Goldberg SL, Tobis JM. Intracoronary stenting without anticoagulation accomplished with intravascular ultrasound guidance. Circulation 1995;91:1676 – 1688. 2. Sankardas MA, McEniery PT, Aroney CA, Bett JHN. Elective implantation of intracoronary stents without intravascular ultrasound guidance or subsequent warfarin. Cathet Cardiovasc Diagn 1996;37:355–359. 3. Nakamura S, Hall P, Gaglione A, Tiecco F, Di Maggio M, Maiello L, Martini G, Colombo A. High pressure assissted coronary stent implantation accomplished without intravascular ultrasound guidance and subsequent anticoagulation. J Am Coll Cardiol 1997;29:21–27.
4. Von Birgelen C, Gil R, Ruygrok P, Prati F, Di Mario C, Van der Giessen WJ, De Feyter PJ, Serruys PW. Optimized expansion of the Wallstent compared with the Palmaz-Schatz stent: on-line observations with two- and three-dimensional intracoronary ultrasound after angiographic guidance. Am Heart J 1996;131: 1067–1075. 5. Go¨rge G, Haude M, Ge J, Voegele E, Gerber T, Rupprecht HJ, Meyer J, Erbel R. Intravascular ultrasound after low and high inflation pressure coronary artery stent implantation. J Am Coll Cardiol 1995 26:725–730. 6. Goods CM, Al-Shaibi KF, Yadav SS, Liu MW, Negus BH, Iyer SS, Dean LS, Jain SP, Baxley WA, Parks JM, Sutor RJ, Roubin GS. Utilization of the coronary balloon-expandable coil stent without anticoagulation or intravascular ultrasound. Circulation 1996;92:1803–1808. 7. Savage MP, Fishman DL, Douglas JS Jr, Pepine CJ, Werner JA, Bailey SR, Rake R, Goldberg S. The dark side of high pressure stent deployment (abstr). J Am Coll Cardiol 1997;29(suppl A):368A. 8. Fernandez-Aviles F, Alonso JJ, Duran JM, Gimeno F, Garcia-Moran E, Paniagua J, Garcimartin I, Mun˜oz JC. High pressure increases late loss after coronary stenting (abstr). J Am Coll Cardiol 1997;29(suppl A):369A. 9. Hoffmann R, Mintz GS, Mehran R, Kent KM, Pichard AD, Satler LF, Popma JJ, Bucher TA, Leon MB. Late tissue proliferation both within and surrounding Palmaz-Schatz stent is associated with procedural vessel wall injury (abstr). J Am Coll Cardiol 1997;29(suppl A):397A. 10. Ellis SG, Vandermael MG, Cowley MJ, Di Sciascio G, Deligonul U, Topol EJ, Bulle TM. Coronary morphologic and clinical determinants of procedural outcome with angioplasty for multivessel coronary disease: implications for patient selection. Circulation 1990;82:1193–1202. 11. Reiber JHC, van der Zwet PMJ, von Land CD, Koning G, van Meurs B, Buis B, van Voorthuisen AE. An overview of coronary quantification techniques as of 1989. In: Reiber JHC, Serruys PW, eds. Quantitative Coronary Arteriography. Dortrecht: Kluwer Academic, 1991:55–132. 12. Reiber JHC, van der Zwet PMJ, von Land CD, Koning G, van Meurs B, Buis B, van Voorthuisen AE. Quantitative coronary arteriography: equipment and technical requirements. In: Reiber JHC, Serruys PW, eds. Advances in Quantitative Coronary Arteriography. Dortrecht: Kluwer Academic, 1992:75–111. 13. Gardner MJ, Altman DG. Confidence intervals rather than P values: estimation rather than hypothesis testing. Br Med J 1986;292:746 –750. 14. Bulpitt CJ. Confidence intervals. Lancet 1987;1:494 – 497. 15. Moussa I, Di Mario C, Di Francesco L, Reimers B, Blengio S, Colombo A. Subacute stent thrombosis and the anticoagulation controversy: changes in drug therapy, operator technique, and the impact of intravascular ultrasound. Am J Cardiol 1996;78:13–17. 16. Kimura T, Yokoi H, Nakagawa Y, Tamura T, Kaburagi S, Sawada Y, Sato Y, Yokoi H, Hamasaki N, Nosaka H, Nobuyoshi M. Three-year follow-up after implantation of metallic coronary-artery stents. N Engl J Med 1996;334:561–566. 17. Vrolix M, Piessens J. Usefulness of the Wiktor stent for treatment of threatened or acute closure complicating coronary angioplasty. The European Wiktor Stent Study Group. Am J Cardiol 1994;73:737–741. 18. De Jaegere PP, Serruys PW, Bertrand M, Wiegand V, Kober G, Marquis JF, Valeix B, Uebis R, Piessens J. Wiktor stent implantation in patients with restenosis following balloon angioplasty of a native coronary artery. Am J Cardiol 1992;69:598 – 602. 19. Mintz GS, Hoffmann R, Mehran R, Pichard AD, Kent KM, Satler LF, Popma JJ, Leon MB. In-stent restenosis: the Washington Hospital Center Experience. Am J Cardiol 1998;81(7A):7E–13E. 20. Goldberg SL, Di Mario C, Hall P, Colombo A. Comparison of aggressive versus nonaggressive balloon dilatation for stent deployment on late loss and restenosis in native coronary arteries. Am J Cardiol 1998;81:708 –712. 21. Eeckhout E, Goy JJ, Stauffer JC, Vogt P, Kappenberger L. Comparison of the Wallstent, Palmaz-Schatz stent and Wiktor stent late after intracoronary stenting. Am J Cardiol 1994;74:609 – 612. 22. Anzuni A, Rosanio S, Legrand V, Tocchi M, Coppi R, Bonnier H, Sheiban I, Kulbertus HE, Chierchia SL. Wiktor stent for treatment of chronic total coronary artery occlusions: short- and long-term clinical and angiographic results from a large multicenter experience. J Am Coll Cardiol 1998;31:281–288.
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groups A and B, respectively; difference between means 0.14 mm, 95% confidence interval ⴚ0.01 to 0.29, p ⴝ 0.08). Angiographic follow-up revealed similar MLD and %DS in both treatment groups (MLD, 2.1 ⴞ 0.7 vs 2.2 ⴞ 0.8 mm; %DS, 31 ⴞ 17% vs 30 ⴞ 24% for groups A and B, respectively, p ⴝ NS). Acute stent thrombosis occurred in 2 patients (1%) (1 patient in each group), and subacute thrombosis in 1 patient (0.6%) in group A. There was 1 death in group A, and target lesion restenosis (>50% DS) was observed in 15% of patients with no differences between the groups. In conclusion, this study demonstrated favorable short- and long-term results of Wiktor stent implantation. Despite a trend toward additional initial lumen gain by high-pressure postdilation, this did not translate into a measurable improvement in long-term outcome. 䊚1999 by Excerpta Medica, Inc. (Am J Cardiol 1999;84:644 – 649)
n contrast to numerous stainless steel stents of tubular or mesh design, there are insufficient data Iregarding adjunctive high-pressure balloon dilation in
trial (the Austrian Wiktor Stent Trial) was therefore designed to evaluate whether high-pressure postdilation of the Wiktor stent provides short- and long-term benefits compared with the conventional low-pressure approach.
1– 6
coil stents, such as Wiktor stents. The Wiktor stent, a single-wire tantalum coil stent, has not undergone profound prospective investigations with respect to safety and efficacy of high-pressure stenting. It is conceivable that the coil configuration (in conjunction with other factors, such as different stent composition other than stainless steel) may allow optimal stent deployment without the need for adjunctive highpressure balloon dilation. Furthermore, whether aggressive balloon dilation increases the amount of reactive intimal proliferation and thus leads to even more late lumen loss and higher restenosis needs to be clarified.7–9 This prospective, randomized, multicenter From the Department of Cardiology, University Clinic of Internal Medicine II, Vienna; Second Department of Internal Medicine, Landeskrankenanstalten Salzburg, Salzburg; Department of Internal Medicine, Karl-Franzens-University, Graz; Department of Cardiology, Medical Hospital Wels, Wels; Department of Internal Medicine, University Hospital of Innsbruck, Innsbruck; Second Medical Department, Landeskrankenhaus Klagenfurt, Klagenfurt; and Fifth Department of Internal Medicine, Kaiser-Franz-Josef-Hospital, Vienna, Austria. This study was supported by an educational grant from Medtronic Austria, Vienna, Austria. Manuscript received November 16, 1998; revised manuscript received and accepted May 5, 1999. Address for reprints: Dietmar Glogar, MD, Department of Cardiology, University Clinic of Internal Medicine II, Waehringer Guertel 18-20, A-1090 Vienna, Austria. E-mail: [email protected].
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©1999 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 84 September 15, 1999
METHODS
Study population and protocol: From June 1995 through May 1996, a total of 202 patients were enrolled prospectively in the trial, which was conducted in 7 Austrian centers. All patients had objective evidence of myocardial ischemia and angiographic evidence of a target lesion suitable for stent implantation. Indications for stent implantation included elective (primary) stenting, ⱖ50% stenosis after balloon angioplasty, and threatening or acute vessel closure after balloon dilatation. Exclusion criteria included a reference diameter ⬍2.5 mm by visual estimation, vessels with poor or compromised runoff distal to the target lesion, heavily calcified lesions that would preclude adequate predilatation, and evidence of intracoronary thrombus. Patients with contraindications or intolerance to therapy with aspirin or ticlopidine were also excluded. Patients were randomly assigned by means of cards in sealed envelopes to either low-pressure Wiktor stent placement at low pressures (6 to 12 atm, group A) or to high-pressure postdilation (ⱖ13 atm, group B) after stent deployment at low pressures. A cross0002-9149/99/$–see front matter PII S0002-9149(99)00409-9
over between randomization groups was possible at the operator’s discretion when this was deemed necessary. The investigational protocol was approved by the local ethical committees of each participating center and written informed consent was obtained from all patients. Stent implantation procedure: Coronary angiography and stent implantation procedures were performed according to standard clinical practice in each participating center, by a femoral approach using a 7Fr or 8Fr guiding catheter. All patients were pretreated with aspirin (ⱖ100 mg/day). Pretreatment with ticlopidine (ⱖ250 mg/day) was started on the day of the procedure. In patients scheduled for elective stent implantation, ticlopidine was given beginning 1 or 2 days before the scheduled procedure. During coronary intervention, patients received an intravenous bolus of 10,000 to 15,000 IU of heparin to maintain an activated clotting time of ⬎300 seconds. The Wiktor stent (Medtronic, Kerkrade, The Netherlands) used during this trial is a balloon-expandable stent of helical coil design composed of a single strand of tantalum wire 0.005 inches in diameter and shaped in a sinusoidal wave pattern. The stent is premounted on a semicompliant polyethylene balloon catheter. Two different stent delivery systems were used at the operator’s discretion: a “Gold-X” single-operator-exchange delivery system with a 16-mm Wiktor stent premounted (used in 88% of patients), or a “Prime” over-the-wire system with a 15-mm Wiktor stent (used in 12%). Nominal, low pressures of 6 to 8 atm were used to expand the stent. In group A, investigators were permitted to use further balloon inflations at low pressures (⬍12 atm) after stent insertion when necessary. In patients assigned to group B, however, a further high-pressure balloon inflation (ⱖ13 atm) was required after stent deployment regardless of the initial stent result. Postprocedure medical regimen: There was no strict postprocedure medication protocol to be used during the trial. However, a recommendation was given before the trial: aspirin ⱖ100 mg/day for 6 months and ticlodipine ⱖ250 mg/day for 4 weeks. There were only minor differences in the dose of the antiplatelet regimen used in the participating institutions: Aspirin 100 mg once daily and ticlopidine 250 mg twice daily were given in 4 of the 7 participating centers (60% of the study patients); aspirin 250 mg once daily and ticlopidine 250 mg twice daily in 2 centers (20%); and aspirin and ticlopidine both 250 mg once daily were given in 1 center (20%). Data collection: All demographic, clinical, and procedural data were recorded prospectively on standardized patient case report forms and forwarded to the core laboratory at the Vienna University Hospital Cardiac Catheterization Laboratories. Each investigating institution was visited by study monitors at regular intervals for data collection and to ensure the quality of clinical and angiographic follow-up data. Evidence of target lesion calcifications or dissections and lesion types (classified according to a simplified American
College of Cardiology/American Heart Association score)10 were determined by each operator and indicated on the case report forms. Quantitative angiographic analysis: Quantitative coronary angiographic (QCA) analysis of all procedural and follow-up cineangiograms were performed at the core laboratory with the use of a validated edge-detection program (Cardiovascular Measurement System Version 2.3D, Medis Medical Imaging Systems, Nuenen, The Netherlands), which has undergone extensive validation studies and has been described in detail elsewhere.11,12 Minimal lumen diameter (MLD), reference diameter (by interpolation), percent diameter stenosis, and mean lumen diameter were measured. In stented vessel segments, MLD was repositioned manually within the stent, when it was initially detected outside the stented segment. Calibration was performed in each analyzed cineangiographic frame on contrast-filled catheters as a scaling device to determine the absolute value (in mm) of MLD. All QCA measurements were obtained in identical views at baseline, after stent implantation, and at follow-up, after maximal vasodilation with 0.1 to 0.3 of mg of intracoronary nitroglycerin. End-diastolic frames were selected for analysis from multiple, preferably orthogonal, views that best showed the target lesion with no significant foreshortening and overlapping structures. Mean values were calculated from multiple matched views for all quantitative angiographic variables. Stenoses present at follow-up and located at the proximal or distal outflow of the stent were not measured by means of QCA, but classified as “peri-stent restenosis” and indicated as such on patient case report forms by each operator when a ⱖ50% diameter stenosis was evident by visual inspection. Acute lumen gain was defined as the net difference between the pre- and postintervention MLD, and late lumen loss was defined as the net difference in MLD between the postintervention result and the follow-up angiogram. The ratio of late loss to acute gain was reported as the loss index. Intravascular ultrasonic analysis: Intravascular ultrasound (IVUS) imaging was performed as an optional part of the study protocol in a subset of the patient cohort (n ⫽ 31) after diagnostic coronary angiography and stent implantation. IVUS images were obtained with either mechanical (2.9 or 3.2 F, CVIS, Sunnyvale, California) or phased-array electronic IVUS catheters (3.0 F, EndoSonics, Rancho Cordova, California) after intracoronary administration of 0.1 to 0.2 mg of nitroglycerin and stored on s-VHS videotapes for subsequent off-line analysis. Minimal lumen cross-sectional areas were measured in the narrowest segment within the lesion or stent. Lumen cross-sectional areas from segments proximal and distal to the target lesion or stent were averaged and used as reference values. Absolute values of minimal lesion or stent cross-sectional areas were also expressed as percentages of the reference cross-sectional area. Study end points and statistics: The primary study end point was the angiographic MLD at follow-up. The sample size of 74 patients in each group with
CORONARY ARTERY DISEASE/LOW– VS HIGH–PRESSURE WIKTOR STENT IMPLANTATION
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angiographic follow-up was determined at the outset of the study to detect a 0.3-mm difference in MLD between the 2 randomized groups, with an assumed standard deviation of 0.65 mm, an ␣ error of 0.05, and 80% power. Secondary study end points were: (1) angiographic target lesion restenosis (ⱖ50% diameter stenosis in the stented segment by core laboratory QCA analysis at follow-up); and (2) occurrence of any 1 of the following major adverse cardiac events: death (considered to be cardiac in absence of clear evidence of noncardiac origin), nonfatal myocardial infarction (serum creatine phosphokinase levels twice the upper limit of normal with MB fraction ⱖ6%, and/or development of new pathologic Q waves on the electrocardiogram), lesion-related coronary artery bypass surgery, and target lesion reintervention. For patients experiencing ⬎1 event, the first event reached was considered. All statistical analyses were performed on a pertreatment (as-treated) basis according to the final treatment in order to take into account crossovers from the initial randomization. Continuous variables are expressed as mean ⫾ SD and were analyzed by 2-tailed t tests. To avoid possible errors produced by unequal variances of the means in the 2 groups, the Welch modified t test was applied when necessary, which yielded similar results. The means of QCA and IVUS measurements after stent implantation and at follow-up were compared by the paired t test. This test was also used to compare the means before and after high-pressure postdilation within the patients in group B. The 95% confidence intervals (CI) were calculated.13,14 The Kolmogorov-Smirnov test was applied to compare the 2 groups for distribution of MLD at baseline, after stent implantation, and at follow-up. Categoric variables are reported as percentages and were analyzed by the chi-square test or by Fisher exact tests when necessary. A statistical probability ⬍0.05 was considered to indicate significance. All statistical analyses were performed using a commercially available software package (S-Plus release 3.4, MathSoft, Cambridge, Massachusetts).
RESULTS
Baseline characteristcs: From 202 patients initially
enrolled in the trial, a total of 181 patients were finally included in the trial and eligible for analysis. Seventeen patients were excluded from final analysis; due to protocol violation in 9, withdrawal of the informed consent in 8, and stent delivery failure in 4. Baseline clinical and angiographic characteristics of the study patients are summarized in Tables I and II. Of the 181 patients, 94 (52%) were randomly assigned to group A and 87 (48%) to group B. There were no statistical differences between groups A and B for all baseline clinical and angiographic variables analyzed. Immediate results: A total of 200 stents were placed in 181 patients (1.1 stent/patient). The balloon:artery ratio (ratio of maximal balloon diameter and reference vessel diameter as determined by QCA analysis) was similar in both groups (1.1 ⫾ 0.2 in group A and 1.1 ⫾ 0.2 in group B; p ⫽ NS). Mean maximal balloon 646 THE AMERICAN JOURNAL OF CARDIOLOGY姞
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TABLE I Baseline Clinical Characteristics of Study Patients Group A Group B All Patients (n ⫽ 94) (n ⫽ 87) (n ⫽ 181) No. of randomized Age (yr) Male gender Ejection fraction (%) Diabetes mellitus Hypertension Hypercholesterolemia Smoking Recent myocardial infarction Stable angina Unstable angina 1-vessel disease 2-vessel disease 3-vessel disease Indications for stent Elective Suboptimal angioplasty result Bailout
61 69 60 20 47 47 35 16 54 40 44 39 11
94 ⫾ 10 (73%) ⫾ 14 (21%) (50%) (50%) (37%) (17%) (57%) (43%) (47%) (41%) (12%)
59 70 60 14 39 50 42 11 45 42 53 28 6
87 181 ⫾ 11 60 ⫾ 11 (80%) 139 (77%) ⫾ 14 60 ⫾ 14 (16%) 34 (19%) (45%) 86 (48%) (57%) 97 (54%) (48%) 77 (43%) (13%) 27 (15%) (52%) 99 (55%) (48%) 82 (45%) (61%) 97 (54%) (32%) 67 (37%) (7%) 17 (9%)
30 (32%) 30 (34%) 60 (33%) 57 (61%) 55 (63%) 112 (62%) 7 (7%) 2 (3%) 9 (5%)
TABLE II Baseline Angiographic Characteristics of Study Patients
Coronary artery size (mm) Minimal lumen diameter before procedure (mm) Diameter stenosis (%) Coronary artery stented Left anterior descending Left circumflex Right Saphenous vein graft Target lesion De novo Restenotic Calcium Dissection Lesion type A B C
Group A (n ⫽ 94)
Group B (n ⫽ 87)
All Lesions (n ⫽ 181)
3.0 ⫾ 0.6 1.1 ⫾ 0.5
3.1 ⫾ 0.6 1.2 ⫾ 0.5
3.1 ⫾ 0.6 1.1 ⫾ 0.5
62 ⫾ 15
64 ⫾ 16
63 ⫾ 16
34 (36%) 16 (17%) 44 (47%) 0
23 18 43 3
(26%) (21%) (50%) (3%)
57 34 87 3
(31%) (19%) (48%) (2%)
73 21 33 48
69 18 32 27
(77%) (23%) (37%) (31%)
142 39 65 75
(78%) (22%) (36%) (41%)
(78%) (22%) (25%) (51%)
32 (34%) 51 (54%) 11 (12%)
30 (34%) 40 (46%) 17 (20%)
62 (34%) 91 (50%) 28 (15%)
inflation pressures were 8.9 ⫾ 2.7 atm in group A and 14.6 ⫾ 1.4 atm in group B (p ⬍0.001). A crossover between treatment groups occurred in 7 patients in group A and in 6 patients in group B. Reasons for the crossover from group A to B were insufficient stent results despite postdilations with low pressures requiring further balloon inflations at high pressures. In 6 patients initally randomized to group B, high-pressure postdilation was not performed because of a potential procedural risk of recrossing the stented lesion with a further balloon for high-pressure postdilation. In 2 patients in group B, the balloon burst after Wiktor stent implantation at high pressure, which was not observed in patients in group A. The early (acute and subacute) clinical outcome is shown in Table III. Acute stent thrombosis occurred in 1 patient in group A and in 1 patient in group B. These patients had a nonfatal Q-wave myocardial infarction and underwent repeat angioplasty. One patient in group A SEPTEMBER 15, 1999
TABLE III Early Clinical Outcome Group A Group B All Patients (n ⫽ 94) (n ⫽ 87) (n ⫽ 181) Acute stent thrombosis Subacute stent thrombosis Major adverse cardiac events Death Acute myocardial infarction Coronary bypass surgery Repeat coronary angioplasty
1 (1%) 1 (1%) 2 (2%) 0 2 (2%) 0 0
1 (1%) 0 1 (1%) 0 1 (1%) 0 0
2 (1%) 1 (1%) 3 (2%) 0 3 (2%) 0 0
experienced a nonfatal Q-wave myocardial infarction due to subacute stent thrombosis and was subsequently referred to coronary artery bypass surgery. The QCA results are summarized in Table IV. No significant differences were found between groups A and B for all final QCA measurements after the procedure. A trend toward a larger mean lumen diameter within the stent was found for group B (p ⫽ 0.08). In group B, the MLD increased from 1.2 ⫾ 0.5 mm at baseline to 2.7 ⫾ 0.6 mm immediately after stent insertion at low pressures (p ⬍0.01), which was slightly but not significantly lower than the MLD in group A. After high-pressure postdilatation there was a further increase in MLD to 2.9 ⫾ 0.5 mm (difference between means, 0.24 mm, 95% CI 0.16 to 0.32, p ⬍0.05). The cumulative frequency distributions of MLD for groups A and B are depicted in Figure 1. The distribution curves were essentially identical for both groups at baseline. After stent implantation, however, a significant larger MLD was found in group B for distribution ranges below the 30% quartile. (p ⫽ 0.0116). In 31 patients (17% of total study cohort; 14 and 17 patients in groups A and B, respectively), IVUS examination was performed after diagnostic coronary angiography and stent implantation. There were no differences in baseline lumen cross-sectional areas between groups A and B (4.6 ⫾ 1.9 and 4.3 ⫾ 1.4 mm2 for groups A and B, respectively; difference between means, 0.36 mm2, 95% CI ⫺1.56 to 0.84). After stent implantation, the final lumen cross-sectional area, expressed both as an absolute value and as a percentage of the reference cross-sectional area, was slightly larger in group B. These differences, however, were not significant: 6.7 ⫾ 1.4 mm2 (70 ⫾ 24%) in group A versus 7.4 ⫾ 1.5 mm2 (79 ⫾ 11%) in group B, difference between means 0.72 mm2 (9.4%), 95% CI ⫺0.34 to 1.78 mm2 (⫺3.9% to 22.7%). Similar to the findings from the QCA analysis, comparison of the cross-sectional areas before and after high-pressure postdilation within group B revealed a significant larger lumen cross-sectional area after high-pressure postdilation. The lumen cross-sectional area had increased from 6.1 ⫾ 1.2 mm2 before to 7.4 ⫾ 1.5 mm2 after high-pressure postdilation (difference between means 1.28 mm2, 95% CI 1.09 to 1.47, p ⫽ 0.048),
and when expressed as a percentage of the reference, from 68 ⫾ 8% to 79 ⫾ 11% (difference between means 11%, 95% CI 9.2 to 12.8, p ⫽ 0.019). Long-term results: Long-term clinical follow-up was achieved in all eligible patients, and follow-up angiography was performed in 154 patients (85%; 76 and 78 patients in groups A and B, respectively) at an interval of 7 ⫾ 3 months after Wiktor stent implantation for both groups. Angiographic and clinical follow-up results are listed in Tables IV and V. The follow-up QCA analysis revealed an MLD of 2.1 ⫾ 0.8 mm and a percent diameter stenosis of 31 ⫾ 21% for the total study population, with no significant differences between the 2 groups. In addition, the cumulative distribution curves of MLD, which was shifted to the right in group B immediately after stent implantation, renarrowed at follow-up, thus revealing no between-group difference (Figure 1). Late lumen loss, loss index, and net lumen gain were not significantly different between groups A and B. Target lesion restenosis, as previously described, was present in a total of 28 patients (14 patients in each group, 15%). There was 1 sudden death in group A at 1 month after stent implantation. No coronary bypass surgery and no acute myocardial infarctions were recorded in either group during the follow-up period. Repeat angioplasty of the stented vessel segment was performed in 13 and 12 patients (both 14%) in groups A and B, respectively, driven by clinical signs of ischemia and/or angiographic evidence of restenosis as assessed visually by each operator-investigator. The overall incidence of major adverse cardiac events at follow-up was 14%, with no difference between the 2 groups (Table V).
DISCUSSION The present study is the first to investigate in a prospective, randomized fashion the short- and longterm benefit of high-pressure implantation of a singlewire coil stent compared with the conventional lowpressure approach. Our results demonstrate favorable clinical and angiographic outcomes with the Wiktor stent, revealing a low incidence of adverse events and target lesion restenosis, with no differrences between the low- and high-pressure randomized groups. Immediate clinical and angiographic results: The incidence of acute or subacute stent thrombosis (2%), with no difference between groups, in the present trial was comparable to results from other tubular or coil stents15,16 and remarkably lower than those observed in previous published studies of the Wiktor stent for bailout procedures or restenotic lesions.17,18 This may be attributed to refinements and improvements over the past few years in poststent medical treatment, and procedural technique and equipment in addition to other factors such as multiple stenting, different stent indications, or patient profile. Recent observations suggest that a more complete stent expansion with the use of high-pressure balloons should lead to improved strut/vessel contact even without IVUS guidance.2,3 This technique seems to
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TABLE IV Quantitative Angiographic Results Group A (n ⫽ 94) Minimal lumen diameter (mm) Baseline After stent implantation Follow-up* Mean lumen diameter (mm) Baseline After stent implantation Follow-up Reference diameter (mm) Baseline After stent implantation Follow-up Percent diameter stenosis (%) Baseline After stent implantation Follow-up Acute lumen gain (mm) Late lumen loss (mm) Net lumen gain (mm) Loss index
Group B (n ⫽ 87)
Difference Between Groups (mean [95% CI])
All Lesions (n ⫽ 181)
1.1 ⫾ 0.5 2.8 ⫾ 0.5 2.1 ⫾ 0.7
1.2 ⫾ 0.5 2.9 ⫾ 0.5 2.2 ⫾ 0.8
0.01 [⫺0.14 to 0.16] 0.11 [⫺0.03 to 0.25] 0.05 [⫺0.18 to 0.28]
1.1 ⫾ 0.5 2.9 ⫾ 0.5 2.1 ⫾ 0.8
1.9 ⫾ 0.5 3.3 ⫾ 0.6 2.7 ⫾ 0.7
2.02 ⫾ 0.5 3.5 ⫾ 0.5 2.8 ⫾ 0.7
0.10 [⫺0.05 to 0.25] 0.14 [⫺0.01 to 0.29] 0.03 [⫺0.17 to 0.23]
2.0 ⫾ 0.5 3.4 ⫾ 0.5 2.8 ⫾ 0.7
3.0 ⫾ 0.6 3.4 ⫾ 0.6 3.0 ⫾ 0.7
3.1 ⫾ 0.6 3.5 ⫾ 0.5 3.1 ⫾ 0.6
0.06 [⫺0.11 to 0.23] 0.10 [⫺0.06 to 0.26] 0.04 [⫺0.16 to 0.24]
3.1 ⫾ 0.6 3.4 ⫾ 0.5 3.1 ⫾ 0.7
0.7 ⫺0.8 ⫺0.7 0.10 0.07 0.05 0.02
63 17 31 1.7 0.7 1.0 0.4
62 17 31 1.7 0.7 1.0 0.4
⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾
15 8 17 0.6 0.6 0.7 0.4
63 16 30 1.8 0.8 1.0 0.4
⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾
16 9 24 0.5 0.8 0.8 0.4
[⫺3.9 to 5.3] [⫺3.3 to 1.7] [⫺6.8 to 5.4] [⫺0.07 to 0.27] [⫺0.14 to 0.28] [⫺0.18 to 0.28] [⫺0.10 to 0.14]
⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾
16 8 21 0.6 0.7 0.7 0.5
*Number of patients with angiographic follow-up was 76 (81%) in group A, 78 (90%) in group B, and 154 (85%) in total.
certain benefit of high-pressure postdilatation on immediate outcome can be demonstrated by analysis of the frequency distribution functions for MLD (Figure 1), which illustrates an improvement in the immediate angiographic result by high-pressure application in patients with a relatively small postintervention MLD (⬍2.7 mm). Furthermore, MLDs and areas, as measured by QCA and IVUS, respectively, were slightly smaller in the high-pressure group immediately after stent insertion at low pressures, but improved significantly after high-pressure postdilatation. Long-term outcome: Several investigators have highlighted a potential drawback of high-pressure stenting based on concerns that high-pressure balloon inflation may increase vessel wall injury and reactive neointimal formation, eventually FIGURE 1. Cumulative frequency distribution of MLD at baseline (Pre), after stent leading to a higher late lumen loss.7–9,19 implantation (Post), and at follow-up (Fup) for groups A and B. There was no A recently published unicenter retrospecdifference in baseline distribution between the 2 groups, but after stent implantation, the curve for group B is shifted to the right, particularly in ranges below tive analysis comparing “aggressive” the 30% quartile (p ⴝ 0.0116). At 6-month follow-up, the difference narstent deployment techniques using overrowed below the significance level. sized balloons (⬎1.15 balloon/artery ratio) or high-inflation pressures (ⱖ12 atm) with “nonaggressive” stent implantation confer a greatly reduced rate of stent thrombosis, which strategies has revealed no increase in late lumen loss may eliminate the need for systemic anticoagulation and or restenosis after aggressive stent implantation.20 its complications. We have found that the final lumen Consistent with this finding, our results show no sigdimensions as measured by both QCA and IVUS did not nificant differences in late outcome between the 2 differ significantly between the high- and low-pressure randomized groups. No statistical differences in folgroups immediately after stent implantation. Although a low-up MLD could be detected between the low- and trend toward a greater lumen gain could be observed for high-pressure groups at follow-up, not only with refinal MLD and mean lumen diameter in the high-pres- spect to absolute diameters or percent diameter stenosure group than in the low-pressure group, neither sis, but also with regard to the frequency distribution reached the level of statistical significance. However, a of the follow-up MLD (Figure 1). The overall target 648 THE AMERICAN JOURNAL OF CARDIOLOGY姞
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TABLE V Occurrence of Adverse Cardiac Events and Angiographic Restenosis
Follow-up (mo after procedure)* Target lesion restenosis In-stent restenosis Peristent restenosis Major adverse cardiac events Death Acute myocardial infarction Target lesion revascularization
Group A (n ⫽ 94)
Group B (n ⫽ 87)
All Patients (n ⫽ 181)
7⫾3
7⫾3
7⫾3
14 11 3 14
(15%) (12%) (3%) (15%)
14 9 5 12
(16%) (10%) (6%) (14%)
1 (1%) 0
0 0
13 (14%)
12 (14%)
28 20 8 26
(15%) (11%) (4%) (14%)
1 (0.6%) 0 25 (14%)
*Clinical follow-up was achieved in 100% of eligible patients and angiographic follow-up was available in 76 patients (81%) in group A, 78 (90%) in group B, and 154 (85%) in total.
lesion restenosis and reintervention rates (15% and 14%, respectively) in our study compare favorably with those reported in previous follow-up studies of Wiktor stents.17,18,21 A similar restenosis rate was found in a recently published multicenter study of the Wiktor stent in chronic total coronary occlusions, when patients with multiple stents (45% of total study population) were disregarded.22 This finding, in conjunction with the encouraging follow-up results of the present trial, may testify to the long-term effectiveness of Wiktor stent implantation even in non–“Benestentlike” lesions. Acknowledgment: We are grateful to Klaus Felsenstein, PhD, Institute of Statistics, Technical University of Vienna, Austria, for statistical advise and critical review of the manuscript.
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CORONARY ARTERY DISEASE/LOW– VS HIGH–PRESSURE WIKTOR STENT IMPLANTATION
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