(Circulation. 1999;100:918-923.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
From the 1. Medizinische Klinik rechts der Isar der Technischen Universität (J.D., H.S., J.P., E.A.); the Deutsches Herzzentrum (A.K., F.J.N., S.E., J.M., R.B., A.S.); and the 1. Medizinische Klinik, Klinikum Großhadern der Ludwig-Maximilians-Universität (P.B., G.S.), Munich, Germany.
Correspondence to Dr Josef Dirschinger, 1. Medizinische Klinik rechts der Isar der TU, Ismaningerstraße 22, 81675 München, Germany.
| Abstract |
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Methods and ResultsConsecutive 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 nonQ-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).
ConclusionsThe 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.
Key Words: stents balloon thrombosis restenosis trials
| Introduction |
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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 |
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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.
Angiographic Evaluation
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.
Statistical Analysis
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
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
2
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.
| Results |
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6 atm in the actual balloon pressure used,
and the distribution of this parameter in either group is
displayed in Figure 1
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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 nonQ-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
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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
).
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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.
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| Discussion |
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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.
Conclusions
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.
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