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(Circulation. 1995;91:2140-2150.)
© 1995 American Heart Association, Inc.
Articles |
Long-term Luminal Renarrowing After Successful Elective Coronary Angioplasty of Total Occlusions
A Quantitative Angiographic Analysis
Presented in part at the 66th Scientific Sessions of the American Heart Association, Atlanta, Ga, November 8-11, 1993.
From the Catheterisation Laboratory, Thoraxcenter, Erasmus University, and the Department of Epidemiology and Biostatistics, Cardialysis (R.M.), Rotterdam, The Netherlands.
Correspondence to Prof P.W. Serruys, MD, PhD, FACC, FESC, Catheterisation Laboratory, Thoraxcenter, Erasmus University Rotterdam, Postbus 1738, 3000 DR, Rotterdam, The Netherlands.
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Abstract |
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 Top Abstract IntroductionMethods Results Discussion References |
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Background The long-term angiographic outcome after successful dilatation of coronary occlusions remains unclear. The objective of this study was to examine long-term restenosis after successful balloon dilatation of coronary occlusions at a predetermined time interval with quantitative angiography and compare this with a control population of stenoses.
Methods and Results The study population comprised 2950 patients (3583 lesions) prospectively enrolled in and successfully completing four major restenosis trials (86% quantitative angiographic follow-up). Cineangiographic films were processed and analyzed at a central core laboratory with the use of an automated interpolated edge detection technique. The study population comprised 266 occlusions (7%) defined as total when there was absent anterograde filling beyond the lesion (109 lesions) and functional (157 lesions) when faint, late anterograde opacification of the distal segment was seen in the absence of a discernible luminal continuity; 3317 lesions were defined as stenoses (93%). Restenosis was significantly higher after successful dilatation of occlusions than of stenoses. With the categorical (>50% diameter stenosis at follow-up) approach, the restenosis rate was 44.7% in occlusions compared with 34.0% in stenoses (P<.001; relative risk, 1.575; CI, 1.224 to 2.027). Similarly, the absolute loss (defined as the change in minimal lumen diameter between post coronary angioplasty and follow-up; in millimeters, mean±SD) (0.43±0.68) in occlusions was significantly higher than in stenoses (0.31±0.51, P<.001), as was the relative loss, defined as the change in minimal lumen diameter between postangioplasty and follow-up, adjusted for the vessel size (0.17±0.28 versus 0.12±0.20, P<.001). The higher restenosis rate in the occlusions group was due predominantly to an increased number of occlusions at follow-up angiography in this group (19.2% compared with 5.0% for stenoses, P<.001). Within the occlusions group, there were no significant differences in long-term outcome between total and functional occlusions (restenosis rate, 45.0% versus 44.6%; reocclusion rate, 23.9% versus 15.9%; absolute loss, 0.53±0.69 versus 0.36±0.67; relative loss, 0.21±0.28 versus 0.15±0.28; P=NS).
Conclusions These results indicate that successfully dilated coronary occlusions, both total and functional, have a higher rate of angiographic restenosis at 6 months than stenoses. This is due chiefly to a higher rate of occlusion at follow-up angiography in this group of lesions. Measures aimed at reducing restenosis after successful dilatation of coronary occlusion should be focused in this direction.
Key Words: angioplasty • occlusions • angiography
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Introduction |
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TopAbstractIntroductionMethods Results Discussion References |
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After the introduction of coronary angioplasty by Grüntzig et al in 1979,1 the indication for its use were at first tentatively and subsequently more strikingly expanded to include patients with total occlusions.2 3 4 5 6 Although a number of factors are known to influence the acute success rate,4 7 8 9 relatively little is known regarding long-term luminal renarrowing after successful dilatation of total occlusions. A number of studies have investigated this, but uncertainty continues with restenosis rates in the literature varying from 20% to 65%.2 3 5 6 10 11 12 13 14 15 16 17 This variation has three primary sources. First, most studies have been retrospective analyses that use small patient numbers and no control group.2 3 11 12 15 16 Second, the angiographic follow-up rates have been low and performed for the recurrence of symptoms rather than at a predetermined time interval, thus introducing important selection bias.5 6 17 Finally, some have used visual assessment to estimate angiographic severity, which is subject to wide interobserver and intraobserver variability.18 This study attempted to overcome these limitations by using a validated automated edge detection technique to evaluate restenosis prospectively in a large series of patients undergoing successful balloon angioplasty and routine follow-up angiographic assessment at a predetermined time interval. Furthermore, a control cohort of patients with stenoses was used to directly compare the long-term results.
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Methods |
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TopAbstractIntroductionMethods Results Discussion References |
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Patients
The study population comprised 3582 patients with significant primary stenoses in native coronary arteries who were prospectively enrolled in four major restenosis trials19 20 21 22 and who underwent successful coronary angioplasty (postprocedural stenosis <50%). These trials demonstrated that active therapy had no effect on restenosis or clinical outcome in the first 6 months after balloon angioplasty, so for the purposes of this study, the data for the active and placebo groups were pooled. Men or women were eligible for study entry if they were symptomatic or asymptomatic with stable or unstable angina pectoris and proven angiographically significant narrowing in one or more major coronary arteries. Informed consent was obtained in all cases before the coronary angioplasty procedure. Patients with evolving myocardial infarction and significant left main disease were excluded from the study.
Angioplasty Procedure and Follow-up Angiography
Coronary
angioplasty was performed with a steerable, moveable
guide wire system by the femoral route. Standard balloon catheters were
used. The choice of balloon type and brand, inflation duration, and
inflation pressure was left to the discretion of the operator. Patients
were followed up for 6 months; then a follow-up study was performed. If
symptoms recurred within 6 months, coronary angiography was performed
earlier. If no definite restenosis was present and the follow-up
time was less than 4 months, the patient was asked to undergo further
coronary arteriography at 6 months.
Quantitative Angiography
In total, three coronary angiograms
were obtained for each
patient—before and after percutaneous transluminal coronary
angioplasty (PTCA) and at angiographic follow-up. To standardize the
method of data acquisition and to ensure exact reproducibility of the
angiographic studies, measures were taken as previously described, and
all angiograms were processed in a central angiographic core
laboratory.19 20 22 The angiograms were
recorded in such a
manner that they were suitable for quantitative analysis by the
computer-assisted CORONARY ANGIOGRAPHY ANALYSIS
SYSTEM, which was described and validated
earlier.23 24 Because the computer algorithm cannot
measure total occlusions, a value of 0 mm was substituted for the
minimal lumen diameter and a value of 100% for the pre-PTCA percent
diameter stenosis. In these cases, the post-PTCA reference diameter was
substituted for vessel size.
Definitions
Total Occlusion
As in previous
studies, total occlusions were divided into
absolute occlusions (Thrombolysis in Myocardial Infarction [TIMI]
flow grade 0) where no anterograde filling beyond the lesion was
visible and functional occlusions (TIMI grade 1) where faint, late
anterograde opacification of the distal segment was present in the
absence of a discernible luminal continuity.17 25
Occlusion at Follow-up Angiography
Occlusion at
follow-up angiography was defined as the presence
of an absolute or functional occlusion at the previously dilated
angioplasty site on angiographic follow-up.
Angiographic
Parameters Assessed
Vessel size refers to the reference diameter of
the relevant
coronary segment and is represented by the interpolated
reference diameter pre-PTCA because this is the closest and most
objective approximation of the disease-free vessel wall.
Minimum luminal diameter (MLD) is the point of maximal luminal narrowing in the analyzed segment.
Many criteria have been proposed for the assessment of restenosis.26 27 28 For the purposes of this study, two approaches were used: the categorical approach with the traditional cutoff point of >50% diameter stenosis at follow-up and a continuous approach that used absolute and relative loss, which reflect the behavior of the lesion during and after angioplasty and may be more representative of the pathological process involved during follow-up.28 29
Absolute gain and absolute loss represent the improvement in MLD achieved at intervention and the absolute change during follow-up respectively, measured in millimeters. Absolute gain is post-PTCA MLD minus pre-PTCA MLD. Absolute loss is post-PTCA MLD minus MLD at follow-up.
Relative gain and relative loss depict the improvement in MLD achieved at intervention and the change during follow-up respectively, normalized for vessel size. Relative gain is (post-PTCA MLD minus pre-PTCA MLD) divided by vessel size. Relative loss is (post-PTCA MLD minus MLD at follow-up) divided by vessel size.
The absolute net gain is the MLD at follow-up minus pre-PTCA MLD. The net gain index is the net gain normalized for the vessel size. The net gain index is (MLD at follow-up minus pre-PTCA MLD) divided by vessel size.
The loss index is the relation of late loss to acute gain: loss index is (MLD at follow-up minus post-PTCA MLD) divided by (post-PTCA MLD minus pre-PTCA MLD).
Statistical Analysis
Data were analyzed with the SAS
statistical
software package. Categorical variables are presented as absolute
numbers (%). Continuous variables are expressed as mean value±SD.
Differences between groups were evaluated with adjusted
2 tests for categorical variables and Student's
t tests for continuous variables. The contributions of
clinical, angiographic, and procedural variables to the categorical
outcome parameters were evaluated with logistic regression
analysis. For the continuous outcome parameter (absolute loss),
multiple linear regression analysis was used. Categorical variables
were dichotomized and entered into the analysis as indicator
variables with values of 0 and 1. Selection of variables was achieved
in a stepwise fashion. The adjusted R2 was used
as the criterion for model selection. Probability values <.05 were
considered significant.
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Results |
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TopAbstractIntroductionMethods Results Discussion References |
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Patient Characteristics and Clinical Follow-up
The study population comprised 2950 patients (3583 lesions, 1.21 lesions per patient) who successfully completed the study and had follow-up quantitative angiography. The overall angiographic restudy rate was 86% of all patients undergoing successful PTCA. We found that 266 lesions in 249 patients out of 3583 lesions in 2950 patients complied with the angiographic definition of total occlusion. Of these, 109 were absolute and 157 were functional total occlusions.
Tables
1
and 2 summarize the clinical and
angiographic characteristics of the 249 patients with occlusions
compared with the 2701 with stenoses. Patients with total occlusions
were younger and had a significantly higher rate of previous myocardial
infarction than patients with stenoses. Furthermore, the duration of
angina in this group was significantly shorter than in stenoses.
Additionally, the presence of thrombus either before or after PTCA was
significantly higher in occlusions. Of the procedural characteristics,
the nominal size of the largest balloon was significantly higher in
stenoses, while the total number of balloon inflations required, total
duration, and maximum inflation pressure were higher in occlusions.
Within the occlusions group, there were no significant differences
between lesions with total and functional occlusions.
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Seventy-one
(28.5%) of the patients with successfully dilated total
occlusions and 598 (22.1%) of the patients with stenoses had clinical
end points (additional PTCA, coronary artery bypass graft [CABG]
surgery, acute myocardial infarction, or death) during follow-up. The
difference was statistically significant (P=.026). The
individual components of death, myocardial infarction, CABG, and
re-PTCA were 0%, 3.6%, 3.6%, and 21.3%, respectively, for
occlusions and 0.2%, 2.8%, 2.4%, and 16.7%, respectively, for
stenoses. The differences in the individual clinical end points between
the two groups were also statistically significant (P=.022).
Fig 1 summarizes the time course of clinical end points.
Although the mean time to clinical follow-up was similar in the two
groups, when we compared the pattern of occurrence of clinical end
points by way of the log-rank test, clinical end points in the
occlusions group were found to occur earlier than in stenoses
(P=.022).
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Interestingly, when lesions that went on to occlude at follow-up angiography were excluded from the analysis, 50 patients (25.1%) with occlusions and 541 patients (21.1%) with stenoses reached a clinical end point, and the difference was no longer statistically significant (P=.217). The individual clinical end points and the time to a clinical end point were also no longer significantly different (P=.238 and .214, respectively).
Quantitative Angiographic Analysis
A mean of 2.12 matched
angiographic projections per lesion had
satisfactory quantitative analysis performed at the central
Angiographic Core Laboratory before and after PTCA and at follow-up
(Table 3). The reference diameter was significantly
lower in occlusions than in stenoses, and this difference remained at
follow-up. As expected, the MLD increased substantially more after
dilatation of occlusions than of stenoses, which was reflected in the
substantially greater relative gain. Nevertheless, the post-PTCA MLD
was significantly lower in occlusions, perhaps reflecting the smaller
vessel diameter in this group (Fig 2a). When this was
taken into account, the percent stenosis after PTCA was similar in both
groups (Fig 2b). At follow-up, previously occluded lesions
deteriorated
significantly more in terms of both absolute and relative loss (Fig
3, Table 3), resulting in a smaller follow-up
MLD and
higher percent stenosis (Fig 2a and 2b, Table
3). Thus, in addition to
restenosis being higher when the continuous, absolute, and relative
loss approach was used, the restenosis rate when the categorical
approach was used was also significantly higher (44.74% in occlusions
compared with 33.95% in stenoses; P<.001; relative risk,
1.575; CI, 1.224 to 2.027).
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Although angiographic restenosis was higher in occlusions than stenoses, there were no significant differences in the presentation of restenosis between the two groups. Of recanalized total occlusions with angiographic restenosis, 40% were symptom-free, while 18.5% complained of angina and 41.5% had a clinical end point. This compares with 39.9%, 18.7%, and 41.4%, respectively, for stenoses with angiographic restenosis.
The higher restenosis rate in the occlusions was due predominantly to an increased number of occlusions at follow-up angiography in this group (19.2% versus 5.0% for stenoses, P<.001). Thus, recanalized occlusions accounted for 23.5% of all occlusions at follow-up angiography even though they formed only 7% of the total study population. The relative risk for occlusion at follow-up angiography was 4.503 (95% CI, 3.196 to 6.344).
Subgroup Analysis of Occlusions Group
Subgroup analysis of
the occlusions group revealed 109
absolute and 157 functional occlusions (Table 4). The
reference diameter after angioplasty was significantly higher in
absolute than in functional occlusions, but this difference did not
persist to follow-up angiography. There were no significant differences
in the MLD or percent stenosis after PTCA or at follow-up (Table
4)
between the two groups. The categorical restenosis rate (>50%
diameter stenosis at follow-up) was almost identical (44.95% versus
44.59%) in the two groups. Although the reocclusion rate in absolute
occlusions tended to be higher than in functional occlusions (23.9%
versus 15.9%), this did not reach statistical significance
(P=.06). By use of the continuous measurements of
restenosis, the absolute and relative loss tended to be lower in
functional occlusions (Table 4), resulting in a significantly
higher
net gain index and a significantly lower loss index.
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Univariate and Multivariate Analyses of Restenosis in Total
Occlusions
Univariate analysis of the available clinical-,
procedural-, and lesion-related characteristics was performed to assess
whether any of these variables were associated with an increased
categorical restenosis rate (Table 5). The only
significant associations were with a shorter duration of angina, a
longer balloon total inflation time, higher residual stenosis after
PTCA, and a lower relative gain. Stepwise logistic regression
analysis was used to further evaluate the relation between this
dichotomous definition of restenosis and the above variables, as well
as all other clinical, lesion, and procedural characteristics. The
number of diseased vessels and the percent stenosis after PTCA were
positively related; duration of angina (in days) was negatively related
to the probability of restenosis at follow-up (Table 6).
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Univariate analysis of clinical, procedural, and lesion
characteristics related to absolute loss showed the only significant
associations to be with total inflation time (P=.0004),
presence of thrombus (P=.0039), post-PTCA MLD
(P=.0144), duration of angina (P=.0262), left
anterior descending coronary artery location (P=.0418), and
lesion calcification (P=.0443). Multiple linear regression
analysis was used to further evaluate absolute loss. Of the
variables assessed, total inflation time (in seconds) and the presence
of thrombus were both positively related to absolute loss (Table
6
).
Univariate and Multivariate Analysis of Occlusions at Follow-up
Angiography
The finding that the higher restenosis rate after
dilatation of
occlusions was due predominantly to an increased number of reocclusions
at follow-up angiography in this group prompted us to examine a number
of variables predictive of reocclusion (Table 7). The
clinical characteristics of the two groups were similar, although
lesions that went on to reocclude had a shorter duration of angina
(27±52 versus 74±132 weeks). Procedural characteristics were
also
similar, although lesions that went on to reocclude required a longer
balloon inflation (537±478 versus 373±294 seconds). Logistic
regression analysis was performed for the above and for all other
clinical, angiographic, and procedural parameters thought to be
associated with the occlusion at follow-up. Of these variables, the
total inflation time (in seconds) was positively related and the
post-PTCA reference diameter (in millimeters) was negatively related to
reocclusion at follow-up angiography (Table 6).
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Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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Our study specifically addressed the problem of long-term luminal renarrowing after dilatation of total coronary occlusions in a large patient population with a control group, a high angiographic follow-up rate, and quantitative angiography at a predetermined time interval. We demonstrated using both a categorical and a continuous approach that restenosis is significantly greater after balloon dilatation of occlusions than of stenoses. Furthermore, we also showed that this is mainly the result of an increased rate of occlusion at follow-up angiography, which is specifically related to total inflation time and reference diameter after intervention. We also demonstrated that restenosis and reocclusion occur to an equal extent in both absolute and functional occlusions. These findings support and expand our current understanding of the long-term angiographic outcome after successful angioplasty of coronary occlusions.
Our overall restenosis rate of 44.7% with the categorical (>50% diameter stenosis) approach compares with the previously reported recurrence rate of 65% from our center3 and is within the 20% to 65% range described previously.2 3 5 6 10 11 12 13 14 15 16 Our restenosis rate, however, is significantly lower than those of the two largest studies published to date,5 6 perhaps as a result of our high angiographic follow-up rate. With univariate analysis, a number of risk factors have been postulated for the higher restenosis rate after dilatation of chronic occlusions. These include anatomic factors such as lesion location (left anterior descending and circumflex)6 14 and absence of functional occlusion,6 procedural factors such as multivessel dilatations6 and increased balloon inflations at higher pressures,10 and residual stenosis after intervention.6 12 14 15 A final risk factor is thought to be the presence of collateral vessels, which may exert competitive pressure even after they are no longer visibly functional30 and thus lead to an increased restenosis rate.
Univariate analysis in our study confirmed significant associations between the categorical definition of restenosis (>50% diameter stenosis at follow-up) and a shorter duration of angina, a longer balloon total inflation time, higher residual stenosis after PTCA, and a greater relative gain. Multivariate analysis, however, suggested that the only significant positive relations were with the number of diseased vessels and the percent stenosis after PTCA, while duration of angina was negatively related to the probability of restenosis at follow-up. The positive relation between the number of diseased vessels and the percent stenosis after PTCA with a categorical definition of restenosis is in keeping with previous studies in both occlusions6 and stenoses.31 The negative relation with duration of angina is also in keeping with previous studies suggesting a positive relation between recent onset of symptoms and a higher risk of restenosis.32 33 34
Interestingly, when we looked at the absolute loss as a marker of restenosis, an outcome measure that may better indicate the underlying pathological process involved, the above variables were no longer significant. The only significant relations were found to be with total inflation time and the presence of thrombus. Both of these were positively related to the subsequent absolute loss. The duration of balloon inflation as a positive risk factor may represent the sum total of the lesion characteristics and a more difficult, more complex procedure with a consequently higher risk of occlusion, thereby markedly influencing the absolute loss. In keeping with this is the fact that we also demonstrated total inflation time to be positively related to the subsequent risk of occlusion at follow-up angiography. The positive relation between the presence of thrombus and the subsequent absolute loss may also reflect a greater likelihood of subsequent occlusion, although we were unable to demonstrate this in our study. Previous studies, however, showed thrombus to be a risk factor for subsequent occlusion,35 36 perhaps acting as a nidus for further platelet deposition.
The main reason for the significantly higher rate of angiographic restenosis in recanalized occlusions in our study was the high rate of occlusion at follow-up angiography in this group (19.2% versus 5.0% after dilatation of stenoses). A number of reasons may account for this. First, this group may represent a subset of the total population that has an intrinsic hematological propensity to thrombosis. Although our laboratory data did not confirm this, there are other hematologic factors such as fibrinogen levels that we did not measure that may influence reocclusion covertly.35
Second, there are substantial morphological differences between lesions,37 which may have considerable influence on the subsequent risk of occlusion. Angiography provides little information on this or on the pathway of subsequent recanalization, which may vary from subintimal to periatheromatous and transatheromatous.38 What effect these variables may have on the subsequent reocclusion and indeed restenosis rates is unknown. Differences in these lesion characteristics may be reflected in the total inflation time, which was significantly higher in lesions more likely to reocclude.
Third, the coronary vasomotor responses after balloon angioplasty of chronic total occlusions may be abnormal. Distal vasoconstriction occurs frequently after angioplasty and correlates well with coronary perfusion pressure, suggesting that chronic hypoperfusion resets epicardial coronary autoregulation and that restoration of normal perfusion pressure after PTCA may provoke reflex vasoconstriction,39 thus precipitating early reocclusion.
Finally, the increased reocclusion rate may relate to local flow dynamics. The reference diameters before and after PTCA and at follow-up were significantly lower in occlusions than in stenoses. Furthermore, within the occlusions group multivariate analysis suggested that there is a negative relation between vessel size and subsequent risk of reocclusion. Thus, successfully dilated occlusions in larger vessels were less likely to reocclude than those in smaller vessels. This is in keeping with experimental work that suggested that smaller vessel diameters and hence higher shear rates favor local platelet activation and deposition,40 41 resulting in a greater likelihood of occlusion.
In addition to being responsible for the higher rate of angiographic restenosis, the high reocclusion rate in recanalized occlusions also seems to have been responsible for the higher rate of clinical events in this group of patients. Patients with recanalized occlusions had a significantly higher proportion of clinical events, mainly in terms of myocardial infarction, CABG, and repeated PTCA. Furthermore, these occurred earlier in occlusions than in stenoses. When patients with occlusions that went on to occlude at the time of follow-up angiography were removed from the analysis, the differences between the two groups were no longer significant, suggesting that the excess risk relates to the higher rate of occlusion at follow-up angiography. Interestingly, despite the higher rate of reocclusion in recanalized occlusions, there were no significant differences in the presentation of restenosis between the two groups, with approximately 40% of patients with angiographic restenosis in both groups being symptom-free.
Although studies of total occlusions suggest that there are important differences in the acute success rates between total and functional occlusions,7 8 our data suggest that in terms of restenosis and reocclusion, there is little difference between the two groups. Although reocclusion after successful dilatation of total occlusions was higher than in functional occlusions (23.9% versus 15.9%), this did not reach statistical significance. However, there was a tendency for functional occlusions to mount less of a fibroproliferative response, which was reflected in the significantly greater net gain index and lower loss index. The cause for this is unclear but is likely to reflect differences in the underlying pathological substrate.
Clinical Implications
Up to 20% of patients undergoing
diagnostic catheterization
have one or more total occlusions; thus, they make up 10% to 20% of
the total angioplasty population.42 Furthermore, in
multivessel disease, they may make the difference in referring the
patient for angioplasty or for CABG surgery. Although great attention
has been paid to increasing the acute success rate with the use of
sophisticated new devices such as the low-speed rotational
angioplasty43 and the Excimer laser,44
relatively little attention has been paid to long-term restenosis and
its amelioration. Our results suggest that the higher restenosis in
these lesions is likely to relate in part to the very high rate of
occlusion at follow-up angiography in this group. Thus, it suggests
that if we can identify these lesions and stop reocclusion, then the
angiographic and clinical courses of recanalized total occlusions are
likely to be similar to those of stenoses. The question of how we do
this, however, is a vexing one. The clinical course in our patient
population and previous studies would suggest that reocclusions tend to
occur early.45 A number of pharmacological and mechanical
approaches have been tried. Ellis and colleagues17
demonstrated that drug therapy with aspirin, dipyridamole, or warfarin
did not influence the overall restenosis rate. In a prospective study,
Di Sciascio and colleagues46 demonstrated that restenosis
is not modified by a longer balloon inflation time. A more recent study
assessed the value of coronary stenting for dissection with threatened
closure following recanalization of total occlusions.47
The restenosis rate at follow-up was high at 57%, as was the recurrent
occlusion rate (20%). When stenting was used routinely after
recanalization of chronic total occlusions and hence when vigorous
anticoagulation was used, the restenosis rate was low at 24% in a
small patient population (65 patients) with an 80% angiographic
follow-up rate.48 Thus, whether the reocclusion rate can
be ameliorated by additional (eg, stenting) or alternative percutaneous
revascularization techniques (high-speed rotational atherectomy or
laser angioplasty) with or without concomitant pharmacological therapy
remains to be established.
Study Limitations
A number of limitations of the present
study are to be
acknowledged. First, the study was a retrospective analysis of
prospectively gathered data and hence is subject to the limitations
inherent in any retrospective study.
Second, there were minor variations in the entry criteria of the studies. In CARPORT and PARK, for example, patients were randomized before PTCA, whereas in MERCATOR and MARCATOR, patients were entered into the trial only after a successful angioplasty procedure.19 20 21 22 Thus, we are unable to comment on clinical, angiographic, or procedural factors influencing the acute success rate of the procedure. Furthermore, patients taking part in large multicenter studies like these are selected in certain ways; therefore, care needs to be taken in extrapolating our results to the broader angioplasty population.
Third, for obvious reasons, the reference diameter in the occlusions group before PTCA could not be reliably measured, so we took the reference diameter after dilatation as the reference diameter before dilatation. The statistical analyses remain valid, however, because even if we substitute the post-PTCA reference diameter for the pre-PTCA reference diameter in the stenoses group, the significant differences between the two groups remain.
Fourth, because of the nature of the data, we unfortunately are unable to comment on whether certain previously documented risk factors for restenosis such as the degree of collateral supply11 or the measured coronary wedge pressure49 50 may relate to reocclusion rather than to long-term restenosis.
Finally, data from the active therapy group and the placebo group were amalgamated. Although the drugs did not seem to influence the overall restenosis rate, the Ketanserin in the PARK study and the thromboxane A2-receptor blocker in the CARPORT studies may have had a covert influence on the reocclusion rate after dilatation of occlusions that we were unable to detect.
Nonetheless, we believe that the merging of the data is justified because the data amalgamated were common to all studies and the angiographic criteria were standardized, with one central laboratory performing the quantitative angiographic analysis in all studies. Furthermore, the resulting large study population provides a unique opportunity to obtain accurate quantitative angiographic data at a predetermined time interval in a field where such few data currently exist.
Conclusions
These results indicate that successfully dilated
coronary
occlusions, both total and functional, have a higher rate of
angiographic restenosis at 6 months than stenoses. This is due chiefly
to a higher rate of occlusion at follow-up angiography in this group of
lesions. Measures aimed at reducing restenosis after successful
dilatation of coronary occlusions should therefore be focused in this
direction.
|
Acknowledgments |
|---|
Dr Violaris is the recipient of a 1992-1994 Wellcome Trust International Research fellowship. We gratefully acknowledge the continually high-quality quantitative angiographic analysis from the staff of the Angiographic Core Laboratory at Cardialysis, Rotterdam, and the sponsorship of Glaxo Group Research Ltd, Middlesex, United Kingdom; F Hoffmann-La Roche Ltd, Basel, Switzerland; and Janssen Research Foundation, Beerse, Belgium. We would also like to acknowledge the work of the 31 European, 40 American, and 7 Canadian centers that participated in the CARPORT, MERCATOR, MARCATOR, and PARK studies, without whose assistance this study would not have been possible. A full list of participating centers can be found in References 19 through 22.
Received October 5, 1994; revision received November 21, 1994; accepted December 3, 1994.
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References |
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TopAbstractIntroductionMethods Results Discussion References |
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