A Randomized Comparison of Direct Stenting Versus Stenting with Predilatation in Native Coronary Artery Disease: Results from th

In the last decade, coronary stenting has evolved from a bailout procedure following balloon angioplasty into an elective strategy for the treatment of all lesions located in vessels with an angiographic reference diameter larger than 3.0 mm.1,2 The standard procedure for stent implantation includes balloon predilatation to facilitate positioning of the stent delivery system at the target lesion; more recently, however, the strategy of stenting without predilatation has become possible due to the availability of new generations of flexible stents, securely crimped on low-profile balloons. This technique, called “direct stenting” (DS), has the potential advantage of reducing costs and radiation exposure.3–6 Moreover, preliminary observations suggest that DS may reduce the incidence of restenosis by lowering the endothelial trauma in comparison to dilatation followed by stenting.7–9 This study addressed the feasibility, efficacy and cost effectiveness of this strategy using the Crossflex LC stent. Methods Patients. The study is a randomized, prospective multicenter trial including seven Italian centers; it was designed to evaluate the efficacy of DS in comparison to the conventional strategy of stenting after predilatation. The study protocol was approved by the institutional Ethics Committee of each participating center and all patients gave informed consent. Patients were considered eligible for inclusion if they complained of angina and/or had objective evidence of myocardial ischemia. Angiographic inclusion criteria were the presence of 1 or 2 de novo or restenotic lesions with diameter stenosis > 50% and Procedural protocol. At the beginning of the procedure, patients received an intravenous bolus of heparin (70–100 U/kg) that was eventually supplemented according to activated clotting time values (targeted at > 200–250 seconds). All patients received double oral antiplatelet therapy with aspirin 100 mg and ticlopidine 250 mg twice daily (or clopidogrel 75 mg once daily) starting at least 3 days before the procedure and continuing for 4 weeks; all patients received aspirin indefinitely. Multiple stent implantation was allowed if required. The stent used (Crossflex LC, Cordis Corporation, Miami, Florida) is a laser-cut slotted tubular stent with good visibility and flexibility provided by the stent design (sinusoidal elements with strut thickness of 0.005´´ linked by connecting bridges creating a double-helical strengthening structure). The stent is premounted and securely crimped on a low-compliance balloon, resulting in a stent balloon assembly characterized by low profile (from 0.04´´ for the stent crimped on the 3.0 mm delivery system to 0.05´´ for the 4.0 mm diameter balloon). The device was available in 12, 17 and 27 mm lengths and in 3.0, 3.5 and 4.0 mm diameters. In the DS group, the stent was gently pushed to cross the lesion; if the attempt was not successful, the stent was retrieved into the guiding catheter, a dilatation with a low-profile balloon was performed and then the same stent was readvanced to the target lesion. In the PS group, predilatation was performed with low-profile balloons; balloon size (diameter and length), number and pressure of inflations were chosen according to investigators’ preferences. In all cases, the stents were deployed by inflating the stent delivery balloon at high pressures (recommended at least 10–12 atm). If necessary, post-dilatation with high-pressure balloons or with larger balloons was allowed to achieve angiographic optimization. Matched orthogonal views were used for quantitative analysis (QCA) before and after treatment using contrast-filled 6 or 8 French catheters for calibration. Angiography was performed after nitroglycerine (100–200 µg) or isosorbide dinitrate (1–3 mg) intracoronary infusion. Angiograms were analyzed offline in an independent angiographic core laboratory (Mediolanum Cardio Research, Milan, Italy) with the validated automated edge-detection system CMS, version 4.0 (Medis, Medical Imaging System, Leiden, The Netherlands). Definitions and endpoints. The primary endpoint was to demonstrate a reduction of procedural time, radiation exposure time and cost with equivalent procedural and clinical outcomes in the DS arm in comparison to the PS arm in the treatment of de novo or restenotic single or double lesions in native coronary arteries. The secondary endpoint was to analyze the 6-month rate of major adverse clinical events (MACE), i.e., death, myocardial infarction and need for target vessel revascularization (angioplasty or coronary bypass surgery) (TVR). Cardiac events were monitored throughout the follow-up period and analyzed at 30 days and 6 months. Procedural success was defined as angiographic success (residual diameter stenosis after Crossflex LC stent implantation Statistical analysis. Data were expressed as means ± standard deviations for continuous variables and as frequencies for categorical variables. Comparisons were performed with the Student’s t-test for continuous data or Pearson’s Chi-square test for discrete data. Statistical significance was accepted for a 2-sided value of p Baseline clinical and angiographic characteristics. Between January 1999 and February 2000, a total of 271 patients were enrolled in the study: 140 patients were randomized to the DS group, and 131 to the PS group. Baseline clinical and qualitative angiographic characteristics of the patients are reported in Tables 1 and 2, respectively. Baseline QCA measurements are listed in Table 3. The two groups were well matched with respect to all these characteristics. The majority of the lesions were type A or B1 by the American College of Cardiology/American Heart Association classification.11 Procedural outcome. Crossover to PS was required in 22 of the 166 lesions (13.2%) enrolled in the DS group because of inability to cross the target lesion without predilatation. In all cases, the stent was retrieved into the guiding catheter without problem and no stent loss occurred. After dilatation with a low-profile balloon, the same stent was then successfully deployed in all cases. The 22 crossover lesions had a smaller MLD (0.82 ± 0.35 mm versus 1.02 ± 0.45 mm; p = 0.02) and a higher degree of percent diameter stenosis (72 ± 11% versus 65 ± 12%; p = 0.03). In the PS group, stent deployment was also performed successfully in all cases. During the hospital stay, three non-Q wave myocardial infarctions were recorded in both groups (2.1% versus 2.3%; p = NS), and no other adverse clinical events were observed. Thus, the final procedural success was 98.9% in the DS group and 98.7% in the PS group (p = NS). As shown in Table 2, stent length, stent diameter and maximal balloon pressures were similar in the 2 groups; additional post-dilatation with a high-pressure, non-compliant balloon or with a larger balloon was performed more frequently in the DS group in comparison to the PS group (p Mid-term clinical and angiographic outcome. Clinical follow-up was completed in 119/140 (85%) and in 113/131 (86%) of the enrolled patients in the DS and PS groups, respectively. No MACE were recorded during the first month after hospital discharge. After 6 months, target lesion revascularization was required in 7 patients in the DS group and in 4 patients in the PS group (p = NS). In all cases, revascularization was performed by repeat PTCA. No deaths or MI were recorded. Angiography was repeated in 39/140 patients (45/166 lesions) in the DS group and in 52/131 patients (59/152 lesions) in the PS group. Quantitative angiographic data and comparisons with pre- and post-procedural measurements are reported in Table 3. No differences were observed between the 2 groups for any of the examined variables. Discussion In patients with 1 or 2 native coronary artery lesions, this study indicates that direct stenting is associated with a significant reduction (18.8%) of the global procedural cost, with procedural and clinical outcomes equivalent to the outcome obtained with the standard approach. The cost reduction was mainly due to the lower number of balloons employed in the direct stenting arm. In this study, predilatation was required in 13.2% of the lesions initially assigned to direct stenting, a crossover rate similar to the rate of predilatation observed in other observational or randomized studies, which report crossover rates varying from 3–20%, largely depending on lesion selection and stent characteristics.3–6,12–22 According to our analysis, stenosis severity and no other clinical and angiographic characteristics were potential predictors of the need of predilatation. Operator experience with this technique may also play an important role, since good selection, manipulation and deep intubation of the guiding catheter may be required to force the stent through severe or calcified lesions. In addition, the full confidence of the operator, based on previous experience, that the particular stent used will not come off the delivery balloon, is an important factor to increase the success rate. In this study, most operators had limited experience with the Crossflex LC at the time the trial started and it was recommended to avoid all risk of damaging or losing the stent. The importance of operator experience has been highlighted by Laarman et al.,16 who reported on a large consecutive series of cases performed with AVE GFX II stents; they compared the first half to the second half of their experience with direct stenting and reported a decrease of crossing failure from 20.1% to 9.9% throughout the study period. In the DS group of this study, a larger number of balloons was used for post-dilatation, which was required in 17.0% of cases. It is likely that an incorrect judgment of the true vessel size before predilatation may occur as a consequence of distal vessel collapse due to severe translesional gradient. Focal balloon technology, with tapering outside the stent or ultra-short balloon shoulders, may reduce the risk of distal dissection and the percentage of cases done with undersized stent delivery balloons. Other potential advantages of direct stenting in comparison to the standard strategy have been described. Direct stenting in vein grafts23–25 or during acute myocardial infarction and acute coronary syndromes26–29 may improve the procedural outcome by reducing the chances of embolization of thrombus or friable material. However, in our study, including mainly elective procedures, we did not observe any difference in procedural results, namely in Q-wave or non-Q wave myocardial infarctions. Results from animal studies have suggested that the smaller vessel trauma and lower endothelial damage induced by direct stenting may result in a lower proliferative response and thus in less restenosis.7–9 In our experience, no differences were noted between the 2 groups in restenosis rate or in late loss, and the need for target vessel revascularization after 6 months was similar in the 2 groups. However, it must be observed that these events were not the primary endpoints of the present study. In addition, angiographic follow-up controls were limited and mainly performed in patients with recurrence of symptoms or evidence of myocardial ischemia. The similar clinical and angiographic outcomes have been confirmed by other randomized studies addressing the same topic; to our knowledge, not a single trial has shown a statistically significant difference in restenosis rate between the two different treatments.3,4,6,12 Study limitations. Since we employed only 1 stent design, our findings cannot be extended to other stent types. In the last few years, improvements in balloon and stent designs have reduced stent profile and increased stent flexibility and trackability. The last generation of premounted stents may further reduce the need for predilatation and postdilatation and may broaden the indications of direct stenting to include more complex lesions. Conversely, in the first trials on antiproliferative coatings with predominant drug storage and release on the outer side of the stent struts, the use of direct stenting was prohibited to avoid scratches and damage to the stent coating.30 A second limitation is that only selected lesions were included in the present study; thus, our results could not be extrapolated to a broader spectrum of lesions. In addition, the definition of non-Q wave myocardial infarction that was in use at the time the study commenced has now been universally replaced by more stringent criteria and may have underestimated a reduction of events in the DS group. Finally, the study protocol did not require a systematic angiographic follow-up after 6 months, and our information about restenosis is limited to the repeat angiograms that were mainly performed in patients symptomatic for angina or with evidence of myocardial ischemia in non-invasive tests. Conclusion. Direct stenting is a safe and feasible technique for the treatment of selected lesions in native coronary arteries. Our results indicate a high rate of technical success and good mid-term results that are comparable to those obtained after a conventional predilatation-stenting strategy. The observed efficacy of direct stenting in reducing procedural costs is mainly due to the lower number of balloons used while procedural time; radiation time and amount of contrast are only slightly and not significantly reduced. Improvements in stent design may further decrease the need for predilatation and increase the number of lesions amenable to treatment with direct stenting.

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