Influence of Balloon Pressure During Stent Placement in Native Coronary Arteries on Early and Late Angiographic and Clinical Outcome
A Randomized Evaluation of High-Pressure Inflation
Background—High-pressure dilatation is considered a better stent placement strategy, but this has not yet been proved by appropriately designed studies. The objective of this randomized trial was to assess the role of high-pressure dilatation in the early and late outcome of patients undergoing coronary stent placement.
Methods and Results—Consecutive patients with coronary stent placement were randomly assigned to high- (15 to 20 atm, 468 patients) or low- (8 to 13 atm, 466 patients) balloon-pressure dilatation. The primary end point of the study was the event-free survival at 1 year. Secondary end points were the incidence of stent thrombosis at 30 days and angiographic restenosis (≥50% diameter stenosis) at 6 months. The incidence of stent thrombosis was 1.7% in the high-pressure and 1.9% in the low-pressure group (relative risk 0.89; 95% CI 0.30 to 2.56). During the first 30 days, although there was no significant difference in the incidence of Q-wave myocardial infarction, the incidence of non–Q-wave infarction was 6.4% in the high-pressure and 3.4% in the low-pressure group (relative risk 1.87; 95% CI 1.02 to 3.42). The restenosis rate was 30.4% in the high-pressure and 31.4% in the low-pressure group (relative risk 0.97; 95% CI 0.75 to 1.26). Event-free survival at 1 year was not significantly different between the groups, with 78.8% in high-pressure patients and 75.5% in patients assigned to low-pressure dilatation (hazard ratio 0.85; 95% CI 0.65 to 1.11).
Conclusions—The systematic use of high-balloon-pressure inflation (15 to 20 atm) during coronary stent placement is not associated with any significant influence on the 1-year outcome of patients undergoing this intervention.
The enthusiasm engendered by the initial randomized trials demonstrating the advantages of coronary stenting over conventional percutaneous transluminal balloon angioplasty (PTCA) was overshadowed by the increase in bleeding complications associated with the anticoagulation therapy imposed by the thrombogenic nature of the stent.1 2 Improvement in the rheology of the stented coronary lumen3 was a first logical attempt to reduce the risk of stent thrombosis and the need for aggressive anticoagulation. Colombo and his team4 5 were the first to propose high-pressure dilatation as a strategy that ensures complete stent apposition, better flow characteristics, and decreased risk of thrombosis and obviates the anticoagulation. This strategy was rapidly embraced by the large community of interventional cardiologists and became an integral part of recent recommendations on coronary stenting.6 The switch to the high-pressure strategy, however, has coincided with the introduction of ticlopidine plus aspirin as a poststenting therapy. The demonstration of the pivotal role of platelets in stent thrombosis7 8 and of the superiority of the combined antiplatelet therapy over anticoagulation for its prevention9 10 necessitates specifically designed studies to clarify the independent role of high-pressure dilatation in the reduction of the risk for stent thrombosis. High-pressure dilatation may also exert a positive influence on restenosis as a result of the better acute lumen achieved11 and improvement in flow characteristics.12
The objective of this randomized trial was to assess the role of high-pressure dilatation in the early and late outcome of patients undergoing coronary stent placement.
Patients with symptomatic coronary artery disease treated with stenting were eligible for this study. Exclusion criteria were acute 3myocardial infarction (within 48 hours before intervention), target lesion in a venous bypass graft, prior randomization, and unwillingness or inability to provide written informed consent for participation in the trial. The randomization sequence was specified before the study began. All patients were randomly assigned to a balloon-pressure strategy by means of sealed envelope before the intervention. Patients gave informed consent for a routine control angiography at 6 months. The study was conducted according to the principles of the Declaration of Helsinki and was approved by the Ethics Committees at each participating center.
Stent Placement and Poststenting Treatment
During the intervention, patients received intravenous heparin and aspirin. Patients considered at higher risk for stent thrombosis (large residual dissections, thrombus at the stent site) received abciximab. Heparin infusion was continued for 12 hours after the intervention. All patients received 250 mg ticlopidine started immediately after the intervention and continued twice daily for 4 weeks as well as 100 mg aspirin taken twice daily indefinitely.
The stents implanted were those in use in our institutions at the time at which the study was performed. They were all composed of stainless steel material and were multicellular in design. We used the Inflow stent (Inflow Dynamics), Multi-Link stent (Guidant, Advanced Cardiovascular Systems), NIR stent (Scimed, Boston Scientific), Palmaz-Schatz stent (Johnson & Johnson Interventional Systems), and Pura-A stent (Devon Medical). Lesion predilatation with conventional angioplasty balloon catheters was performed before the stent placement. Except for the Multi-Link type, all stents were firmly hand-crimped on conventional balloon catheters before delivery. For Multi-Link stents, the delivery system provided by the manufacturer was used. The balloon size for stent deployment was chosen on the basis of the estimated vessel size in a nondiseased portion. High pressure was defined as a pressure in the range of 15 to 20 atm on the basis of the values used by Colombo et al4 5 and achieved with noncompliant or minimally compliant balloons. Low pressure was defined as a pressure in the range of 8 to 13 atm to allow a safe inflation with conventional angioplasty balloons below the rated burst pressure. The procedural results were assessed by angiography only; no intravascular ultrasound studies were performed. The procedure was considered successful when stent placement was associated with a residual stenosis of <30% and Thrombolysis in Myocardial Infarction (TIMI) flow grade ≥2.
Lesion complexity and calcifications were defined according to Ellis et al.13 Left ventricular function was assessed qualitatively on the basis of biplane angiograms with a 7-segment division; the diagnosis of reduced left ventricular function required the presence of hypokinesia in ≥2 segments. Offline quantitative angiographic analysis was performed by operators not involved in the procedure and unaware of the pressure strategy to which the patient was assigned. Digital angiograms were analyzed with the automated edge detection system CMS (Medis Medical Imaging Systems). Matched views were selected for angiograms recorded before and immediately after the intervention and at follow-up. The parameters obtained were minimal lumen diameter (MLD), reference diameter, diameter stenosis, and diameter of the maximally inflated balloon during stent placement. Acute elastic recoil was measured as the difference between balloon diameter and MLD at the end of the procedure. Acute lumen gain was the difference between MLD at the end of the intervention and MLD before balloon dilatation. Late lumen loss was calculated as the difference in MLD between immediately after the procedure and follow-up.
Definitions and End Points of the Study
The primary end point of the study was event-free survival at 1 year after the procedure. Death, myocardial infarction, and target vessel revascularization (PTCA or aortocoronary bypass surgery) were considered adverse events. The diagnosis of acute myocardial infarction was established in the presence of a clinical episode of prolonged chest pain and a rise in serum creatine kinase (CK) levels to at least twice the upper normal limit or the appearance of ≥1 new pathological Q waves on the ECG.14 CK was determined before and immediately after the procedure, every 8 hours for the first 24 hours after stenting, and then daily until discharge. Target vessel revascularization was performed in the presence of angiographic restenosis and symptoms or signs of ischemia. Cardiac events were monitored throughout the follow-up period. The assessment was made on the basis of the information provided by hospital readmission records, referring physician, or phone interview with the patient. For all those patients who showed cardiac symptoms during the interview, at least a clinical and ECG checkup was performed at the outpatient clinic or by the referring physician.
Secondary end points of the study were based on angiographic outcomes after stenting. First, the incidence of stent thrombosis was assessed during the early 30-day period. The diagnosis was made on the basis of a TIMI flow grade of 0 or 1 at angiography. Second, the incidence of restenosis (defined as a diameter stenosis of ≥50%) was assessed from the 6-month follow-up angiography.
The number of patients included in the study was based on the sample size estimation for our primary end point, the occurrence of any major adverse event during the first year after the procedure. We assumed a 1-year event rate of 20% for patients with low-pressure stenting and 13% for those with high-pressure dilatation. The study was designed to have an 80% power for detecting a significant difference between these 2 strategies with an α level of 0.05, and a sample size of 466 patients for each group was estimated.
All analyses were performed on an intention-to-treat basis. Results are expressed as mean±SD or as proportions (%). The differences between groups were assessed by χ2 test for categorical data and t test for continuous data. The relative risk for an adverse event associated with high-pressure inflation was also calculated. Survival analysis was made by the Kaplan-Meier method. Differences in survival parameters were assessed for significance by means of the log-rank test, and the hazard ratio associated with high-pressure inflation was calculated by Cox regression analysis. Statistical significance was accepted for all values of P<0.05.
Of the 934 patients enrolled in the study, 468 were assigned to high-pressure and 466 to low-pressure dilatation. Table 1⇓ shows the baseline clinical characteristics of the patients, which were comparable between the groups. Table 2⇓ lists the baseline angiographic characteristics of the patients. Diameter stenosis was higher in patients of the high-pressure group, whereas all other data were not significantly different between the groups. Table 3⇓ shows the procedural data. On average, there was a difference of ≈6 atm in the actual balloon pressure used, and the distribution of this parameter in either group is displayed in Figure 1⇓. In 45 patients of the low-pressure group (14 with calcified lesions), the operator considered it more appropriate to use a pressure above the range specified in the study protocol because of suboptimal angiographic results. In 24 of these 45 patients (53%), the balloon pressure used was only 1 atm above the upper limit of 13 atm, ie, intermediate between low and high pressure. In 48 patients of the high-pressure group, the operator used a pressure below the range specified in the study protocol because of increased risk or presence of a progressive dissection or when it was impossible or hazardous to reach the stented lesion with an additional noncompliant balloon. In 20 of these 48 patients (42%), the balloon pressure used was only 1 atm below the lower limit of 15 atm, ie, intermediate between low and high pressure. Thus, in 6.0% of high-pressure patients, we used a pressure within the low-pressure range and in 4.5% of low-pressure patients, a pressure within the high-pressure range.
Early 30-Day Outcome
There were no cases of coronary artery perforation in either group. Table 4⇓ indicates the number of patients with untoward events within the first 30 days after the procedure and the respective relative risk associated with high-pressure inflation. During this period, there was a higher incidence of non–Q-wave myocardial infarction (CK or CK-MB elevation >3 times normal) in the group of high balloon pressure, 6.4%, versus 3.4% in the low-pressure group; relative risk 1.87; 95% CI 1.02 to 3.42. Figure 2⇓ shows the incidence of myocardial infarction defined according to the criteria applied in the EPISTENT trial.8
Angiographic Follow-Up and 1-Year Clinical Outcome
Patients without adverse events within the first 30 days after the procedure were considered eligible for a 6-month angiographic control. It was carried out in 372 (83.0%) of the eligible patients in the high-pressure group and 370 (82.2%) of the eligible patients in the low-pressure group.
The results of the quantitative assessment of the follow-up angiogram are presented in Table 5⇓. The incidence of restenosis was 30.4% in the high-pressure group and 31.4% in the low-pressure group, and the relative risk associated with high-pressure inflation was 0.97 (95% CI 0.75 to 1.26).
As shown in Table 6⇓, our primary end point, event-free survival, was not significantly different between the 2 groups, with 78.8% in patients assigned to high-pressure dilatation and 75.5% in patients assigned to low-pressure dilatation, with a hazard ratio of 0.85 (0.65 to 1.11). Repeat PTCA was required in 77 patients (16.4%) of the high-pressure arm, compared with 78 patients (16.7%) in the low-pressure arm; relative risk of 0.98 (0.72 to 1.35). Primary end-point analysis performed in different subgroups defined by the stent model used, the presence of complex or calcified lesions, or lesions located in small vessels did not show any significant influence of high-pressure dilatation (Table 7⇓).
Table 8⇓ shows the main findings in subgroups defined by the random assignment and actual pressure used. For both study groups, the results achieved in patients in whom a pressure outside the assigned range was applied were not significantly different from those achieved in patients in whom a pressure within the limits specified by the protocol was used.
This randomized study compared 2 strategies of balloon dilatation pressure during stent placement in native coronary vessels of 934 patients with coronary artery disease. It showed that systematic use of high pressure is not associated with any appreciable reduction in the incidence of stent thrombosis and restenosis. Most importantly, the rate of adverse clinical events during the 1 year after the intervention was comparable for both treatment strategies.
High Balloon Pressure and Early Adverse Events
The overall incidence of stent thrombosis within the first 30 days after the procedure was 1.8% in the present study. This is in the range of stent thrombosis rate reported for patients treated with combined antiplatelet agents after stenting.4 5 15 16 We could not show any significant difference in the incidence of this complication between high- and low-pressure inflation, but we should also take into account that this study was not sufficiently powered for the analysis of the secondary end point of stent thrombosis. Earlier observational studies reported a low incidence of stent thrombosis with high-pressure inflation and dual antiplatelet therapy with ticlopidine plus aspirin.5 16 More recently, 2 randomized trials demonstrated the independent preventive effect of ticlopidine plus aspirin against stent thrombosis.9 10 This therapy was particularly beneficial in patients with high risk for stent thrombosis.17
The rates of early clinical events such as death, Q-wave myocardial infarction, and reintervention were also comparable between the 2 groups with different pressure inflation strategies. Another important finding of this study is the higher incidence of CK elevation after stenting with high-pressure inflation, which may be of concern considering the most recent data about its clinical significance.18 Our results, however, should not be interpreted as contradicting a positive role conceived for optimal stent expansion. Bermejo et al19 recently demonstrated with intravascular ultrasound investigation that despite high-pressure deployment, lumen dimensions after stenting are only 57% of the maximum achievable because of inadequate balloon expansion and elastic recoil. These issues were not the focus of the present study, and it remains to be demonstrated which is the best strategy to achieve an optimal stent expansion.
High Balloon Pressure and Restenosis
Final lumen achieved after stenting is one of the most powerful predictors of restenosis at follow-up.20 High-pressure inflation is expected to afford a better lumen at the end of the intervention. In fact, a slight yet significant difference in residual stenosis was verified in the present study in favor of the high-pressure strategy. Conversely, the use of high balloon pressure may engender concerns about a potential exacerbation of the hyperplastic response from the injured vessel wall. The present randomized trial demonstrated that restenosis after coronary stent placement is not a function of the balloon pressure strategy used. All angiographic and clinical indexes of restenosis were comparable between the high- and low-pressure arms. Conversely, our findings did not justify the concerns that this approach may serve as a stimulus for excessive neointimal hyperplasia after stenting.
Limitations of the Study
Studies that assess the role of various pressure inflation strategies during coronary stent placement suffer from the lack of a clear-cut definition of high pressure. The pressure used in the high-pressure arm of the present study complies well with the values applied by the team that proposed this strategy for the first time4 5 and also corresponds to the recent recommendations of the American College of Cardiology Expert Consensus Document.6 Similarly, there is no clear definition of low pressure. In their initial experience, Schatz et al used pressure ranges of 6 to 10 atm21 or 9 to 12 atm.22 Our average inflation pressure of 11.1 atm in the low-pressure group is also comparable to that of 10±8 atm used in the BENESTENT trial1 before the advent of high-pressure strategy.
Even with minimally compliant balloons, balloon size and consequently balloon-to-vessel ratio are not completely independent from the inflation pressure. If both pressure and balloon-to-vessel ratio vary concomitantly, it may be difficult to estimate the independent role of inflation pressure. The results presented here should not be extrapolated to procedures in which the combination of high-pressure inflation with compliant balloons may significantly increase the balloon-to-vessel ratio. Our primary goal was to keep a comparable balloon-to-vessel ratio between the 2 groups and to test the independent role of inflation pressure. Appropriately designed studies are required to evaluate which is the best balloon-to-vessel ratio to be used during coronary stent deployment to achieve an optimal result.
Another limitation of the study is that not all patients have been treated with an inflation pressure within the assigned range. However, the deviation from the predefined range was mostly minimal, and only 6.0% of the high-pressure patients and 4.5% of low-pressure patients crossed over to the opposite inflation pressure range. These data also indicate that a unique inflation pressure strategy may not be applied for all kinds of lesions.
The systematic use of high-pressure inflation during coronary stent placement is not associated with any significant influence on the 1-year outcome of patients undergoing this intervention. Depending on lesion characteristics, the operator may take advantage of a wider range of balloon inflation pressures that may be used to achieve optimal results.
- Received January 14, 1999.
- Revision received May 24, 1999.
- Accepted June 2, 1999.
- Copyright © 1999 by American Heart Association
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