CLINICAL STUDIES
Angiographic and clinical outcome following coronary stenting of small vessels
A comparison with coronary stenting of large vessels
Tatsuro Akiyama, MD*,
Issam Moussa, MD ,
Bernhard Reimers, MD*,
Massimo Ferraro, RT*,
Yoshio Kobayashi, MD*,
Simonetta Blengino, MD*,
Lucia Di Francesco, PhD*,
Leo Finci, MD*,
Carlo Di Mario, MD, PhD, FACC* and
Antonio Colombo, MD, FACC*
* Centro Cuore Columbus, Milan, Italy
Lenox Hill Hospital, New York, New York, USA
Manuscript received December 10, 1997;
revised manuscript received July 1, 1998,
accepted July 29, 1998.
Address for correspondence: Dr. Antonio Colombo, Centro Cuore Columbus, Via M. Buonarotti 48, 20145 Milan, Italy
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Abstract
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Objectives. Stent implantation reduces restenosis in vessels  3 mm compared with balloon angioplasty, but few data are available for stents implanted in vessels <3 mm. The aim of this study was to evaluate immediate and follow-up patient outcomes after stent implantation in vessels <3 mm compared to stent implantation in vessels 3 mm.
Methods. Between March 1993 and May 1996, a total of 1,298 consecutive patients (1,673 lesions) underwent coronary stenting. The study population was divided into two groups based on angiographic vessel diameter. In case of multivessel stenting, patients were randomly assigned only one lesion. Group I included 696 patients (696 lesions) in whom stents were implanted in vessels 3 mm, and group II included 602 patients (602 lesions) in whom stents were implanted in vessels <3 mm.
Results. There was no difference in procedural success (95.4% in group I and 95.9% in group II), or subsequent subacute stent thrombosis (1.5% in group I and 1.4% in group II, p = NS). The postprocedure residual diameter stenosis was 3.31 ± 12.4% in group I and –2.45 ± 16.2% in group II. Angiographic follow-up was performed in 75% of patients, restenosis occurred in 19.9% of patients in group I and 32.6% in group II (p <0.0001). Absolute lumen gain was significantly higher in group I compared to group II, but absolute late lumen loss was similar in the two groups (1.05 ± 0.91 mm in group I vs. 1.11 ± 0.85 mm in group II, p = NS). Subsequently, the loss index was more favorable in group I (0.45 vs. 0.56; p = 0.0006). Independent predictors of freedom from restenosis by multivariate logistic regression in the total population were: larger baseline reference diameter (odds ratio 2.032 p = 0.006), larger postprocedure minimal stent cross-sectional area (odds ratio 1.190, p = 0.0001) and shorter lesions (odds ratio 1.037, p = 0.01). At long-term clinical follow-up, patients with small vessels had a lower rate of event-free survival (63% vs. 71.3%, p = 0.007).
Conclusions. Coronary stenting can be performed in small vessels with a high success rate and low incidence of stent thrombosis. However, the long-term angiographic and clinical outcome of patients undergoing stent implantation in small vessels is less favorable than that of patients with large vessels.
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Abbreviations and Acronyms
| | ACT | = activated clotting time | | CABG | = coronary artery bypass graft surgery | | CI | = confidence interval | | CSA | = cross-sectional area | | ECG | = electrocardiogram | | IVUS | = intravascular ultrasound | | MI | = myocardial infarction | | MLD | = minimum lumen diameter | | PTCA | = percutaneous transluminal coronary angioplasty | | TIMI | = thrombolysis in myocardial infarction |
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Coronary stents have reduced restenosis in focal lesions in vessels with an angiographic reference diameter equal or greater than 3.0 mm compared to balloon angioplasty (1–3). Recently, the benefits of stenting in small vessels, compared to balloon angioplasty, were reported (4). Improvements in stent implantation technique and postprocedural pharmacological treatment reduced stent thrombosis and bleeding complications (5–7), leading to the use of coronary stenting in more complex lesion subsets (8) including lesions in small vessels. Initial reports have suggested a higher incidence of subacute thrombosis and restenosis when stents are implanted in small vessels.
The purpose of this study was to assess the immediate and long-term outcomes of patients undergoing stenting in small vessels and to compare those to the outcomes of patients undergoing stenting in larger vessels using similar technique and postprocedure pharmacological therapy.
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Methods
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Patient population.
Between March 30, 1993, and May 31, 1996, a total of 1,298 consecutive patients (1,673 lesions) underwent coronary stenting at Columbus Hospital in Milan, Italy. All patients had a significant angiographic stenosis (50% diameter stenosis) associated with clinical or objective evidence of myocardial ischemia. Patients were divided into two groups based on the angiographic proximal reference diameter before intervention (in case of multivessel stenting, patients were randomly assigned only one lesion): group I included 696 patients (696 lesions) with reference diameter 3 mm, and group II included 602 patients (602 lesions) with reference diameter <3 mm.
Quantitative angiographic measurements.
Patients received intracoronary isosorbide-dinitrate (2–5 mg) prior to initial postprocedure and follow-up angiograms to achieve maximal vasodilation. The guiding catheter was used for calibration. Measurements were made from an optically magnified image in a single matched "worst" view. Digital calipers (Brown and Sharp, North Kingstown, RI) were used until July 1995 (870 lesions; 67%); subsequently, a computerized quantitative analysis system (QCA-CMS system version 3.0, MEDIS, Leiden, The Netherlands) was used. Previous studies have shown that digital calipers correlate closely with computer-assisted methods with a low interobserver and intraobserver variability (9).
In our laboratory, interobserver reproducibility was assessed by two experienced angiographers who performed blinded measurements of randomly selected coronary segments (n = 20). Intraobserver reproducibility was based on blinded measurements performed at a different time. Intraobserver correlation coefficient (r) was 0.98 (p < 0.0001, 95% CI [confidence interval] 0.96 to 0.99) for reference measurements and 0.91 (p < 0.0001, 95% CI, 0.71 to 0.97) for intrastent minimal lumen diameter. Interobserver correlation coefficient was 0.95 (p < 0.0001, 95% CI, 0.87 to 0.98) for reference measurements and 0.90 (p < 0.0001, 95% CI, 0.68 to 0.97) for intrastent minimal lumen diameter.
Angiographic measurements included proximal and distal reference diameter, minimum lumen diameter (MLD), percent diameter stenosis and lesion length. Lesion length was measured on the baseline angiogram as the distance from the proximal to distal lesion shoulder. Relative gain, relative loss and net gain indexes were also calculated (10). Relative gain represents the improvement in MLD as a result of the intervention normalized for vessel size and is calculated as (postprocedure MLD minus preprocedure MLD) divided by preintervention reference diameter. Relative loss is the change in MLD from postprocedure to the follow-up angiogram normalized for vessel size and is calculated as (post-procedure MLD minus MLD at follow-up) divided by preintervention reference diameter. Loss index reflects the percentage of acute gain that is lost at follow-up and is calculated as (postprocedure MLD minus MLD at follow-up) divided by acute gain. Lesions were characterized according to the modified AHA/ACC (American Heart Association/American College of Cardiology) classification (11).
Intravascular ultrasound equipment and measurements.
A mechanical 3.2F ultrasound catheter (CVIS, Boston Scientific, Sunnyvale, CA) was used. Validation of quantitative measurements and pathologic correlation with ultrasound measurements have both been reported (12,13). Images were initially obtained using a manual pullback. After July 1994, a mechanical pullback system at a constant speed of 0.5 mm/s was used. The position of the catheter on fluoroscopy was used to correlate the ultrasound image with the angiogram and a voice comment was recorded during pullback. The ultrasound runs were stored on 0.5-inch super VHS videotape and immediate quantitative analysis was performed after each pullback.
Lumen and vessel cross-sectional areas (CSAs) were measured with the use of a trackball to outline the lumen-intima interface and the media-adventitia interface, respectively. The smallest lumen area within the stent was selected for measurement in each passage of the intravascular ultrasound (IVUS) catheter. Reference lumen CSAs were measured proximal and distal to the stented segment in the closest and most normal appearing segments. The average reference vessel and lumen CSAs were calculated as the average of the proximal and distal reference vessel and lumen CSAs. Interobserver and intraobserver reproducibility of MLD and lumen CSA measurements have already been reported (14).
Stent implantation procedure.
Intracoronary stenting was performed using techniques previously described (15–17). Patients received aspirin 325 mg and continued their standard antianginal therapy before the stent procedure. A bolus of 10,000 U of heparin was administered after insertion of the femoral sheath. If necessary, a repeat bolus of heparin 2,500 U was given to maintain the activated clotting time (ACT) greater than 250 s. Patients did not receive dextran or dipyridamole before, during or following the stent procedure.
Different stents types were used; the Palmaz-Schatz stent (Johnson and Johnson Interventional Systems, Warren, NJ) was the most frequently used stent (795 lesions; 61.2%). Other stents implanted were the Gianturco-Roubin I stent (Cook Cardiology, Bloomington, IN) (105 lesions; 8.1%); the NIR stent (SciMed, Boston Scientific, Maple Grove, MN) (73 lesions; 5.6%); the Wiktor stent (Medtronic, San Diego, CA) (69 lesions; 5.3%); the Wallstent (Schneider Europe, Bulach, Switzerland) (43 lesions; 3.3%); the AVE Micro stent II (Applied Vascular Engineering, Santa Clara, CA) (42 lesions; 3.2%); the tantalum Cordis stent (Cordis Corp., Miami, FL) (25 lesions; 1.9%); the BeStent (Medtronic, Minneapolis, MN) (18 lesions; 1.4%); the Crown stent (Johnson and Johnson Interventional Systems, Warren, NJ) (7 lesions; 0.5%); the ACS Multilink stent (Guidant, Temecula, CA) (7 lesions; 0.5%); the Angiostent (AngioDynamics, Glens Falls, NY) (4 lesions; 0.3%); the ACT I stent (Progressive Angiography Systems, Menlo Park, CA) (2 lesions; 0.2%), or a combination of different stents (103 lesions; 7.9%). The decision to choose a particular stent type (slotted tube or coil stent) was based on several factors, among which were lesion location (aorto-ostial, side-branch at the lesion site, location at a bend, location distal to a tortuous segment), presence of calcifications and occasionally on the availability of appropriate stent lengths.
After stent implantation, angiographic optimization was performed to achieve a good angiographic result with <20% residual stenosis by visual estimate. Intravascular ultrasound was performed in the majority of cases after optimization of the angiographic result. The IVUS success was defined as the achievement of a final minimum intrastent CSA 60% of the average proximal and distal reference vessel CSA or a final minimum intrastent CSA larger than the distal reference lumen CSA. However, the use of IVUS interrogation after stenting during the period of this study was not based on random assignment but on operator decision; therefore, some patients did not undergo IVUS interrogation. Indications for stenting were defined as previously described (17).
Postprocedure pharmacological therapy.
A total of 1,241 patients (96%) were treated only with antiplatelet medications, ticlopidine and aspirin in 950 patients (77%) and aspirin alone in 291 patients (23%). Before March 1995, a total of 57 patients (5%) were treated with a standard anticoagulation regimen consisting of warfarin for 2 months and aspirin indefinitely. This group included 17 patients with thrombus and slow flow after the procedure, 17 patients with suboptimal final IVUS results, 3 patients with inadequate lesion coverage because of the inability to deliver a stent; the remaining patients were on warfarin for other indications.
Definitions.
Study end points were: 1) angiographic restenosis defined as the presence of 50% diameter stenosis at the treated site at follow-up angiography; and 2) event-free survival defined as survival in the absence of CABG, myocardial infarction (MI) (Q wave or non-Q wave), and repeat intervention. Death was defined as any death irrespective of the cause. A diagnosis of Q-wave MI was made when there was documentation of new pathological Q waves (>0.04 s) on an electrocardiogram (ECG) in conjunction with elevation in creatine kinase to greater than twice the upper limit of normal. A diagnosis of non-Q-wave MI was made when an elevation of the cardiac enzymes to greater than twice the upper limit of normal was documented without the development of new pathological Q waves. Emergency CABG was defined as any CABG performed during the hospitalization of the patient. Acute thrombosis events were angiographic-documented stent thrombosis occurring within 24 h of the procedure. Subacute thrombosis events were angiographically documented occlusions with TIMI flow grade 0 or 1 at the stent site occurring beyond 24 h to 2 months after the stent procedure, or sudden death occurring within 2 months after the procedure.
Statistical analysis.
Data were analyzed with the SAS statistical system software version 6.11. Categorical variables are presented as absolute numbers and percentages. Continuous variables are presented as mean ± SD. Subgroup comparisons were performed by chi-square analysis for categorical variables and by the Student t test for continuous variables. The role of clinical, angiographic and procedural variables in influencing restenosis was evaluated with multivariate logistic regression analysis. First, univariate analysis was performed, then variables that were found to be significant were entered into a stepwised logistic regression model to determine the independent predictors of freedom from restenosis. Probability values <0.05 were considered significant. Kaplan-Meier survival analysis and the log-rank test were used to evaluate the composite end point of death, MI, CABG or target lesion revascularization during the first 12 months after stenting.
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Results
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Patient and lesion characteristics.
The clinical characteristics of the two groups are shown in Table 1. There were no differences in clinical risk factors, ejection fraction, unstable angina and frequency of multivessel disease. As shown in Table 2, there was no difference in lesion type (AHA/ACC), presence of total occlusions, calcification and bifurcations.
Patients who returned for follow-up angiography had similar baseline clinical and angiographic characteristics compared to those who did not return for follow-up (Table 3).
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Table 3 Comparison Between Patients Who Had Follow-up Angiography (Fu+) and Patients Who Did Not Have Follow-up Angiography (Fu–) in the Total Study Population
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Procedural, quantitative angiographic and IVUS analysis.
As shown in Table 4, baseline angiographic reference diameter was 3.43 ± 0.39 mm in group I vs. 2.63 ± 0.29 mm in group II (p < 0.0001), but there was no difference in lesion length or severity. The balloon-to-artery ratio used for final stent expansion was significantly higher in group II compared to group I (1.29 ± 0.20 vs. 1.09 ± 0.14, p < 0.0001), but there was no difference in number of stents per lesion or final pressure used for stent expansion.
The IVUS guidance was used in similar frequency in both groups. The average reference vessel diameter (media to media) by IVUS was 3.78 ± 0.51 mm in small vessels and 4.35 ± 0.58 mm in large vessels (p = 0.001). Accordingly, if the balloon-to-vessel ratio (B/V) was calculated using IVUS vessel size, the B/V ratio would be 0.91 ± 0.12 in small vessels and 0.88 ± 0.10 in large vessels (p = 0.006).
Procedural outcome and short-term events.
High rate of procedural success was achieved in both groups (95.4% in group I and 95.9% in group II). As shown in Table 5, there was no difference in incidence of procedural complications and in incidence of acute and subacute stent thrombosis.
Incidence of angiographic restenosis.
Angiographic follow-up was obtained in 74% and 75% of patients at a mean duration of 5.6 ± 2.0 and 5.6 ± 2.1 months in groups I and II, respectively (p = NS). As shown in Table 6, there was no difference in stent type distribution between the two groups. The quantitative angiographic measurements for lesions that had angiographic follow-up are shown in Table 7. A significantly larger absolute lumen gain was achieved in group I compared to group II (2.42 mm vs. 2.06 mm; p < 0.0001), but the absolute late lumen loss was similar between both groups (1.05 ± 0.91 mm vs. 1.11 ± 0.85 mm, p = NS). This resulted in a more favorable loss index (0.45 vs. 0.56; p = 0.0006) in group I, as shown in Figure 1. Subsequently, the binary restenosis rate was 19.9% in group I vs. 32.6% in group II (p < 0.0001). The incidence of angiographic restenosis varied according to stent design (slotted tubular vs. coil stents) (Fig. 2). For slotted tubular stents, restenosis remained significantly lower in large vessels compared to small vessels (16.7% vs. 27.7%; p = 0.0012). However, there was no statistical difference in restenosis between large and small vessels when coil stents were implanted (32.1% vs. 32.6%; p = NS).
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Figure 2 Restenosis rates with different stent designs in group I (large vessels) and group II (small vessels).
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Also, the incidence of restenosis varied according to the use of IVUS guidance. Restenosis rates were lower when IVUS guidance was used in patients with large vessels and in patients with small vessels, as shown in Table 7. However, the reduction in restenosis was primarily due to achieving an optimal IVUS result. In the large vessel group, restenosis was 15% when an optimal IVUS result was achieved (249 lesions) compared to 24% when an optimal IVUS result was not achieved (101 lesions), p = 0.036. Similarly, in the small vessel group, restenosis was 26% when an optimal IVUS result was achieved (223 lesions) compared to 37% when an optimal IVUS result was not achieved (89 lesions), p = 0.043.
Predictors of freedom from angiographic restenosis.
Table 8 shows a comparison between restenotic and nonrestenotic lesions in all patients who underwent IVUS guided stenting. All clinical, lesion and procedural characteristics that were found to be significantly different between the two groups were entered into a stepwise multivariate logistic regression model, as shown in Table 9. Factors that independently predicted a higher probability of freedom from restenosis were larger baseline reference diameter (95% CI, 1.24 to 3.21, odds ratio 1.996, p = 0.004), larger final intrastent CSA (95% CI, 1.09 to 1.34, odds ratio 1.205, p = 0.0004), and shorter lesions (95% CI, 1.02 to 1.07, odds ratio 1.041, p = 0.001).
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Table 9 Multivariate Predictors of Freedom From Restenosis in Patients With IVUS-Guided Stenting in the Total Cohort: Stepwise Multivariate Logistic Regression Analysis
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Long-term clinical outcome.
Event-free survival during the first 12 months after stenting in each group is shown in Figure 3. Patients with small vessels had a significantly lower rate of event-free survival (63%) compared to patients with large vessels (71.3%), p = 0.007.
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Figure 3 Kaplan-Meier survival curves for the combined end point of death, myocardial infarction, coronary bypass surgery or target lesion revascularization during the first 12 months after stenting in each group.
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Discussion
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The major findings of this study are the following: 1) patients who undergo stent implantation in small vessels have short-term outcome (1 month) similar to patients who undergo stenting in larger vessels; in particular, the incidence of stent thrombosis in small vessels is not higher than that in larger vessels; 2) these results were obtained using a significantly higher angiographic balloon-to-artery ratio for final stent dilatation in small vessels compared to larger vessels; this strategy points to the tendency of the operator to oversize balloons more so in small vessels than in large vessels to attain the maximal lumen gain possible; 3) small vessel stenting is associated with a higher restenosis rate compared to stenting larger vessels; 4) the loss index in small vessels is higher than that in larger vessels; 5) the achievement of a large final CSA inside the stent is a major variable associated with a lower restenosis rate both in large and small vessels; 6) slotted tubular stents perform better in large vessels compared to coil stents; and 7) both stents perform suboptimally in preventing restenosis rate when implanted in small vessels.
Previous studies using coil stents and oral anticoagulation have suggested that stent thrombosis is higher when stents are implanted in angiographically small vessels (18,19). However, using the same regimen a recent subanalysis of the STRESS trial (4) reported a stent thrombosis rate of 3.6% in vessels <3 mm, which is similar to the stent thrombosis rate in the total STRESS population (3.5%). In the present study, the incidence of stent thrombosis was low in both large and small vessels. The low incidence of stent thrombosis in small vessels in this study is in agreement with other reports where aggressive stent expansion was used with postprocedure antiplatelet therapy (20,21). An exception is what was reported in the French registry (6), where stent thrombosis occurred in 10% of patients in whom final stent expansion was performed with balloons <2.5 mm despite using aspirin and ticlopidine therapy. This may represent a subgroup of patients with small vessels in whom undersized balloons were used for stent expansion.
The combination of these observations highlights the importance of appropriate stent expansion particularly in small vessels. The use of IVUS guidance facilitates decision making in terms of balloon sizing, especially in angiographically small vessels that may in fact be large vessels with diffuse atherosclerosis. Therefore, this fact has to be considered when angiography alone is used for balloon sizing.
The incidence of restenosis was significantly higher following the stenting of small vessels compared to stenting of larger vessels. This finding is in agreement with previous studies after standard percutaneous transluminal angioplasty (PTCA) and atherectomy (22,23) but has not been consistently confirmed following coronary stenting (24–29). In the present study, the absolute lumen loss caused by intimal proliferation appears to be similar in small and large vessels. The bigger postprocedural lumen obtained in large vessels compared to smaller vessels is the most possible explanation for the lower restenosis rate seen following the stenting of large vessels. Serial IVUS studies have shown that the main mechanism of restenosis after nonstent coronary interventions is chronic vessel constriction (30,31), whereas after stenting the restenotic process is entirely due to intimal proliferation (32,33). It remains to be explained why stenting elicits a relatively higher proliferative response in small vessels. One possibility is that the process of lumen gain in small vessels requires a higher degree of vessel wall stretch. However, before discussing this issue, it should be pointed out that it would be misleading to look only at the absolute values of lumen gain and loss when evaluating patients with heterogeneous vessel sizes, the reason being that absolute lumen gain is primarily dependent on vessel size, as shown in Figure 4. This means that larger lumen gain could be obtained in large vessels using a lower degree of vessel wall stretch compared to what is needed in a smaller vessel. This concept could be better expressed using the "relative gain ratio," which represents the amount of lumen gain relative to vessel size. A higher relative gain ratio, as found in the small vessel group, means a higher proportional gain (stretch) applied to the vessel wall.
One may argue that, because the higher degree of vessel trauma induced by an aggressive stent expansion strategy (higher balloon-to-vessel ratio) is associated with higher loss index, then perhaps a less aggressive strategy might be preferred. There are several observations that do not support such an argument: 1) in this study, the balloon-to-artery ratio per se was not predictive of restenosis in univariate or multivariate analysis. Conversely, the final minimal CSA within the stent was an independent predictor of freedom from restenosis in the total population regardless of vessel size; and 2) a less aggressive stent dilatation strategy in smaller vessels did not result in lower restenosis in the STRESS trial (4). In that study, the authors reported results of coronary stenting in vessels <3 mm (mean vessel size 2.69 mm). Minimum lumen diameter postprocedure and at follow-up was 2.26 mm and 1.54 mm, respectively, compared to 2.85 mm and 1.73 mm in our study. This resulted in a restenosis rate of 34% in the STRESS subanalysis compared to 28% in patients who had slotted tube stents in our study. This illustrates that a less aggressive dilatation strategy does not decrease restenosis, but in fact may increase it. Therefore, there is little advantage for a more conventional limited stent expansion to limit vessel trauma in small vessels. This strategy is likely to produce a final smaller in-stent CSA with a negative net effect on the incidence of stent thrombosis and restenosis.
Another possible explanation for the higher proliferative response in small vessels is the higher metal density when a stent designed to be implanted in large vessels is used in vessels <3.0 mm. Stents specifically designed to achieve an optimal radial force at a smaller diameter with a lower metal-to-vessel surface ratio have been recently introduced and have a theoretical potential to improve the long-term results. An indirect support to this concept comes from the observation that coil stents had a similar effect on restenosis than slotted-tube stents in small vessels, suggesting that the negative properties of these stents (higher recoil and plaque prolapse) are counterbalanced by the more favorable metal-to-vessel surface ratio.
In the present study, IVUS guidance was used in similar frequency in both small and large vessels. Our findings suggest that patients who had stent implantation under IVUS guidance, in small or large vessels, had lower rate of restenosis compared to patients where IVUS was not used. However, this benefit was primarily present in patients where optimal stent expansion was achieved. Unfortunately, in the small vessel cohort an optimal IVUS result can be achieved in only 71% of lesions. These data indicate that the use of IVUS per se does not necessarily lead to reduction of restenosis unless the information obtained is used appropriately to achieve the maximal lumen gain safely possible. The fact that IVUS guidance was used according to the intention of the operator and not according to random assignment not only sets limitations on this statement but also sets demands for a randomized study to assess this issue better.
Study limitations.
The most important limitation is that this study was performed in a period of rapid technical evolution. Subtle changes in decision making throughout the study period are confounding factors that are difficult to detect. The fact that this study is a retrospective single-center experience based on data that were acquired prospectively immediately after treatment and analyzed by investigators unaware of the future clinical outcome gives uniformity and reliability to these observations. However, this may also introduce an element of uncertainty to the general application of the results to settings where different techniques are used. In addition, the use of IVUS guidance or slotted tube versus coil stents in this study was based on operator decision and not random assignment; therefore, the strength of conclusions made with respect to the effect of these variables on incidence of restenosis is limited. Despite these shortcomings, this study provides clinically relevant information about the impact of vessel size on long-term angiographic and clinical outcome of unselected patients undergoing coronary stent implantation.
Conclusions.
Coronary stenting can be safely applied in small vessels; in particular, immediate success and incidence of subacute thrombosis do not differ in relation to vessel size provided appropriate antiplatelet therapy is given and an optimal result is achieved. Despite these encouraging short-term results, patients who undergo stent implantation in small vessels have an angiographic restenosis rate higher than 30% and a lower rate of event-free survival compared to patients with larger vessels.
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