Clinical Outcomes with Drug-Eluting Stents following Atheroablation Therapies

Treatment with drug-eluting stents (DES) has revolutionized percutaneous coronary intervention (PCI) due to their substantial efficacy in reducing restenosis and the need for repeat revascularization procedures. Despite this benefit, the delivery of DES remains challenging in complex coronary anatomy, including lesions with extensive calcification and eccentricity. In addition, stent placement with DES still does not exclude the potential mechanical complications associated with plaque shift associated with percutaneous revascularization of bifurcation and ostial lesions. While these persistent challenges underscore the ongoing limitations of PCI, they also support the occasional but longstanding use of adjunctive technologies to facilitate balloon angioplasty and stent placement. In particular, catheter-based atheroablative technologies, including excimer laser and rotational and directional atherectomy, have been evaluated in both randomized clinical trials and registries in a variety of complex lesion subsets and clinical settings.¹ However, despite their ability to facilitate device success, treatment with atheroablative therapies has often been associated with higher rates of early major adverse cardiac events (MACE) and intermediate-term restenosis compared with standard care.^1,2 Although atheroablative therapy is still required in a minority of patients to facilitate lesion and device success,³ clinical outcomes among patients treated with both DES and adjunctive atherectomy devices has not been studied. In particular, for patients with complex lesion morphologies in whom use of atherectomy devices may be indicated, whether additional treatment with DES results in comparable clinical outcomes to patients treated with or without DES and no atheroablation is uncertain. We therefore examined clinical outcomes among patients treated with and without DES and atherectomy among patients undergoing percutaneous coronary revascularization in the Duke Database for Cardiovascular Disease. Methods Patient population. Patients included in this analysis represented a broad, unselected population of individuals with coronary artery disease and varied clinical presentation. Patients in the Duke Database for Cardiovascular Disease are routinely followed at 6 months and annually thereafter using mailed questionnaires, telephone interviews or search in the National Death Index for patients whose vital status is unknown. Clinical events are verified using source documentation. Data collection and archiving of clinical variables in the Database were performed according to methods previously described.^4,5 Post-procedure levels of creatine kinase, creatine kinase-MB and troponin-T are routinely evaluated in all patients. Although decisions regarding additional device selection and use of adjunctive pharmacological therapies during the revascularization procedure were according to the operators’ discretion, the practice at our institution regarding the use atheroablative devices is routinely limited to the treatment of complex lesion morphologies (revised American College of Cardiology and American Heart Association lesion classifications B2 and C).⁶ Patients did not undergo routine follow-up catheterization and quantitative coronary angiography was not performed routinely. Patients receiving bare-metal stents (BMS) received a minimum of 4 weeks of aspirin and a thienopyridine (either ticlopidine or clopidogrel), and patients receiving a DES received a minimum of 3 months of aspirin and a thienopyridine if a sirolimus-eluting stent was placed, or a minimum of 6 months if a paclitaxel-eluting stent was placed. Patients were grouped according to the use of atheroablation (either rotational atherectomy, directional atherectomy or laser angioplasty) and stent type (either BMS or DES). Patients who underwent atheroablation and received DES at Duke University Medical Center between April 1, 2003 and January 1, 2005 comprised the case group. Three control groups were randomly identified from patients undergoing PCI at Duke from March 1, 1995 to January 1, 2005: patients who underwent atheroablation and received BMS, patients who did not undergo atheroablation and received DES and patients who did not undergo atheroablation and received BMS. Patients in the control groups were matched to the case group on age, presence of diabetes, lesion length and target vessel type (native vessel or saphenous vein graft). Ethical considerations. The analysis plan for this study was reviewed and approved by the Institutional Review Board of Duke University Medical Center. Statistical analysis. Baseline characteristics were compared across the groups using Chi-square tests for categorical variables and the nonparametric Kruskal-Wallis test for continuous variables. Baseline differences with trend p-values 7 Backward selection was used in model development. Bootstrapping of variable selection was then performed on 200 repeat samples, with replacement using all candidate variables. History of MI, family history of CAD and CAD index were significant (at the 0.05 level) in the resample models 80%, 68% and 51% of the time, respectively. The next highest variable was significant in 39% of the resample models. Internal validation of the final model was performed by bootstrapping the hazard ratios using 200 repeat samples with replacement. Model discrimination was assessed using the c-statistic. All analyses were conducted using SAS, Version 8.2 (SAS Institute, Cary, North Carolina). Results Patient characteristics. From the time of DES availability in April 2003 to January 2005 (the latest period of follow up available), 2,252 PCI procedures involving treatment with at least 1 DES were performed in patients having complete clinical follow up in the Duke Database. Among them, 36 patients underwent DES placement after the use of an atheroablative device. After matching on 5 clinical and angiographic criteria, we identified 42 patients who received BMS with atheroablation, 63 patients who received DES without atheroablation and 71 patients who received BMS without atheroablation. Of the atheroablative techniques used, excimer laser atherectomy was the most common adjunctive procedure, followed by rotational atherectomy and directional atherectomy (44.9% vs. 35.9% vs. 19.2%; p (Cypher™, Cordis Corp., Miami, Florida), and 3 patients were treated with paclitaxel-eluting stents (Taxus®, Boston Scientific Corp., Natick, Massachusetts). Of the patients in the DES/no atherectomy group, 40 patients and 23 patients received sirolimus- and paclitaxel-eluting stents, respectively. Table 1 lists the baseline characteristics of the patients across all 4 groups. There was a higher prevalence of prior PCI, prior coronary bypass surgery, multivessel disease and saphenous vein graft intervention among patients who underwent DES placement after atheroablation. In contrast, there was a lower prevalence of MI within 48 hours prior to PCI in this group. Clinical outcomes. Table 2 lists the MACE rates across the four patient groups. The median duration of follow up was 385 days (25th–75th percentiles, 228–743 days). Although the differences in the incidence of 30-day MACE across the groups did not reach statistical significance, patients who received BMS without atheroablation had the highest 30-day MACE rate, whereas patients treated with DES after atheroablation had the lowest 30-day MACE rate. Regarding 6-month outcomes, these differences persisted but did not reach statistical significance. Figure 1 displays the MACE-free survival curves across the 4 groups, demonstrating the highest event-free survival among patients in the DES/atherectomy group. In an adjusted model, independent predictors of MACE after adjustment for patient and angiographic characteristics included a prior history of MI, family history of coronary artery disease and severity of coronary artery disease. The use of atheroablation was not a predictor of MACE. Model discrimination was good (c-index = 0.73). Discussion These results indicate that among selected patients treated with DES following treatment with directional, rotational or excimer laser atherectomy, clinical outcomes are similar to patients treated with DES and without atheroablation. Further, compared with patients receiving bare-metal stents, treatment with atheroablation prior to DES is associated with a reduction in MACE, principally due to a lower incidence of repeat target lesion revascularization. Thus, in complex lesion morphologies that may not be suitably treated with angioplasty alone, treatment with atheroablative therapies prior to DES placement may be an appropriate method to improve device and lesion success without compromising clinical outcome. Prior studies of atheroablation have not demonstrated an advantage over conventional balloon angioplasty. Bittl and colleagues conducted a systematic overview of 16 randomized trials comparing coronary atherectomy, laser angioplasty and cutting balloon atherotomy with angioplasty and found that atheroablation was not associated with an improvement in survival or long-term MACE rates.¹ They were associated with an increase in periprocedural MI and short-term MACE. The use of adjunctive bare-metal stenting after atheroablation has shown mixed results. Some studies have shown an advantage with optimal lesion preparation and atheroablation prior to stenting,^8–10 while others have demonstrated no advantage with these techniques.^11–13 Over time, the use of atheroablation has declined.¹⁴ This is likely due to improvements in balloon and stent technology that facilitates delivery even in the most complex lesions. Simultaneous with the decline in the use of atherectomy and laser has been an increase in the number of elderly patients and patients with multiple comorbidities undergoing PCI.¹⁵ In some of these patients, lesion preparation with balloon angioplasty does not facilitate stent delivery or does not allow for optimal stent expansion.³ This results in suboptimal PCI and worse long-term outcomes. Our study suggests that atheroablation followed by DES placement can optimize PCI in selected complex patients. Study limitations. Our study has some limitations. First, we did not explore the indication for atheroablation in patients who underwent these procedures. As stated above, the use of these techniques at our institution is rare and reserved only for complex lesions. Second, we did not have systematic angiographic follow up in all patients. However, the purpose of our study was not to evaluate the angiographic outcomes with DES after atheroablation; rather, it was to determine if the use of DES after atheroablation was safe in terms of clinical outcomes. Third, the high prevalence of laser angioplasty and saphenous vein graft intervention in our study suggests that operators were using this technique as an adjunct to stenting rather than to facilitate stent delivery. Since the intent of our analysis was to describe outcomes with DES after atheroablation regardless of indication, this should not diminish our findings. Fourth, although the median length of follow up extended beyond 1 year, we did not examine even longer-term outcomes. Finally, our study is not a randomized trial and should not be interpreted as an endorsement of routine atheroablation prior to DES. Instead, it demonstrates that in selected patients where atheroablation is necessary to optimize stenting, the use of DES can minimize MACE associated with atheroablation. Conclusions The results of this single-center, matched analysis demonstrate that the use of DES after atheroablation is associated with a low rate of MACE. The use of DES was associated with better outcomes compared with BMS, regardless of whether atheroablation was used. This suggests that in selected patients where the use of directional atherectomy, rotational atherectomy or laser angioplasty is necessary to facilitate stent delivery, the use of DES can offset the risk of MACE associated with these atheroablative devices. Acknowledgment. The authors are grateful to Linda K. Shaw and Dr. Kevin Anstrom for statistical guidance, and to Judy Stafford for the creation of datasets from the Duke Database for Cardiovascular Disease.

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