Drug-Eluting Stents Following Rotational Atherectomy for Heavily Calcified Coronary Lesions: Long-Term Clinical Outcomes

ABSTRACT: Background. Rotational atherectomy followed by drug-eluting stent (DES) implantation for complex, severely calcified lesions is a rational combination that has not been sufficiently evaluated. Methods. We investigated 102 consecutive patients with angiographic evidence of heavily calcified lesions that underwent DES implantation following rotational atherectomy at our institution between June 2005 and October 2009, and we examined the long-term clinical outcomes. The major adverse cardiac events monitored were death, myocardial infarction and target lesion revascularization. Results. Patients were 68.8 ± 7.4 years old, 52.9% were diabetic, and 12.7% had chronic kidney disease. Forty-seven patients (46.1%) had three-vessel disease, and 13 (12.7%) had left main coronary artery stenosis. The radial approach was used in 37.3% of cases. The procedure was successful in 97%. In-hospital death occurred in 1 patient (0.9%), and 3 patients (2.9%) developed stent thrombosis. At the mean follow-up period of 15 months (range 1–54), the total cardiac death rate was 4.9%, target lesion revascularization was 8.8% and the incidence of myocardial infarction was 3.9%. The combined endpoint occurred in 12.7% of cases. Conclusion. DES following rotational atherectomy for heavily calcified coronary lesions is a safe and effective procedure that provides good long-term clinical outcomes. J INVASIVE CARDIOL 2011;23:28–32 ———————————————————— Coronary artery stenting with drug-eluting stents (DES) has been shown to be effective in reducing restenosis.¹ The risk of restenosis remains high after coronary stenting in fibrocalcific lesions, since coronary calcium decreases wall compliance and may provide incomplete stent apposition after angioplasty and stenting.^2,3 Vessel modification with rotational atherectomy (RA) prior to stenting is an important strategy in the treatment of severely calcified coronary lesions. RA has shown favorable acute results in facilitating stent delivery and adequate expansion.⁴
The use of bare-metal stents (BMS) after RA has not been linked to satisfactory results, with medium- and long-term rates of restenosis and target lesion revascularization (TLR) exceeding 16–25% in some studies.^5–7 DES have been reported to reduce restenosis and TLR rates both in calcified and non-calcified lesions compared to BMS.^8,9 However, it has not been fully clarified whether the benefits of DES persist after pre-treating calcified coronary lesions with RA. This study examined the outcomes of patients who underwent DES implantation for the treatment of heavily calcified coronary lesions with the use of RA.

Methods

Patients. Between June 2005 and October 2009, we studied a consecutive series of patients with severely calcified de novo coronary lesions who underwent DES implantation following RA at our institution. The lesions were defined as severely calcified by the procedure operator according to qualitative angiographic criteria and classified according to the American College of Cardiology/American Heart Association lesion classification¹⁰ as type B or C lesions, due to the presence of calcium within the vessel wall at the site of the stenosis before contrast injection. Patients with diseases associated with a life expectancy of less than 12 months and those with acute ST-segment elevation myocardial infarction (STEMI) were excluded from this study. Procedure. The procedures were performed after obtaining written informed consent. The choice of artery (radial or femoral) and decision to perform RA were made by the operator. All patients received pretreatment, commenced at least 1 day prior to the procedure, with aspirin (100–300 mg/day) and clopidogrel (a minimum of 300 mg load and 75 mg/day). During the procedure, the patients received anticoagulation with unfractionated heparin (70 UI/kg) or bivalirudin with or without glycoprotein IIb/IIIa inhibitors to achieve an activated clotting time of 250–300 seconds. RA was performed with the Rotablator^® (Boston Scientific-Scimed Corporation, Natick, Massachusetts) by using the smallest burr that was necessary to modify the calcified plaque and facilitate the delivery of other devices, including balloons, stents or intravascular ultrasound (IVUS). Rotational speed ranged between 170,000 and 190,000 rpm and had short passes (Clinical follow up and definitions. Clinical and laboratory data during hospitalization periods and during follow-up were prospectively recorded. Angiographic success was defined as a residual in-stent stenosis 12 Clinical follow up at 30 days, 4 to 6 months and annually was done clinically either by personal visit or telephone. Quantitative angiographic analysis. Quantitative analysis of the angiographic images was performed using the QCA-CMS^® system (MEDIS, Medical Imaging Systems, Leiden, The Netherlands) by two independent cardiologists. The analysis segment included the stent(s) and 5 mm proximal and distal to the stented segment. The percent diameter stenosis (%DS), minimum luminal diameter (MLD), reference vessel diameter and lesion length were measured at baseline and immediately after the procedure. Acute gain was defined as the increase in MLD immediately after intervention. Statistical analysis. The statistical analysis was done with the SPSS 17.0 package (SPSS, Inc., Chicago, Illinois). A descriptive analysis was used. Continuous variables are described as means ± standard deviation (SD) and categorical variables as absolute counts and percentages.

Results

Baseline and procedural characteristics. A total of 128 consecutive patients with de novo severely calcified coronary lesions undergoing RA followed by stent implantation were identified between June 2005 and October 2009. Patients with a risk of bleeding, elective surgery scheduled for the next months and limited life expectancy ( 70 years of age; 52.9% were diabetic and 12.7% had chronic renal failure. In 81 cases (80.2%), the RA was performed outright based on angiographic or IVUS characteristics. Bailout RA was performed in 21 cases (19.8%) due to failure of the balloon to cross the lesion or the inability to properly expand a balloon after crossing the lesion. Angiographic and procedural characteristics are reported in Table 2. Overall, 13 patients (12.7%) had left main coronary artery (LMCA) stenosis, 3 of whom presented with a protected LMCA. The types of DES implanted were paclitaxel-eluting Taxus stents (Boston Scientific-Scimed Corp., Natick, Massachusetts) in 55 patients (53.9%); sirolimus-eluting Cypher stents (Cordis Corp., Miami Lakes, Florida) in 15 patients (14.7%); zotarolimus-eluting Endeavor stents (Medtronic Vascular, Santa Rosa, California) in 17 patients (16.7%); biolimus-eluting BioMatrix stent (Biosensors International Group, Singapore) in 10 patients (9.8%); and everolimus-eluting Xcience V stent (Abbott Vascular, Santa Clara, California) in 5 patients (4.9%). Postdilatation with a noncompliant balloon after coronary stenting was performed in 67 lesions (65.7%). The maximum inflation pressure was 16.3 ± 4.2 atmospheres. Among 11 bifurcation lesions, treatment with a double stent (main vessel and sidebranch) was done in 5 cases. Forty-four patients (43.1%) received additional stenting to treat other coronary lesions without RA during the same procedure. The complete revascularization rate was 84.2%. Quantitative angiographic analysis. Table 3 contains the data from the quantitative angiographic analyses. The reference vessel diameter was 2.66 ± 0.53 mm. Residual stenosis after the procedure was 8.7 ± 5.57%. The lesion length at baseline was 30.4 ± 14.2 mm, and 85.3% of the lesions were > 20 mm. After final stent implantation, the acute gain was 2.03 ± 0.21 mm. In-hospital and late follow-up outcomes. Clinical outcomes are described in Table 4. Angiographic success occurred in 99% of cases. One patient had residual stenosis of 42.4% after the procedure, calculated by quantitative angiographic analysis, and was referred for elective coronary revascularization surgery due to the risk of ST. The procedure was successful in 97% of cases. Dissection requiring repair occurred in 3 patients (2.9%). No perforations occurred during the procedure. In 2 patients (1.9%), significant (> 1.5 mm) sidebranch loss occurred and was resolved by stenting. Prophylactic pacemakers were not implanted. No deaths occurred during the procedure. In-hospital death occurred in 1 patient (0.9%) who had severe systolic dysfunction and multivessel disease (including the LMCA) and died 8 days after the procedure due to acute pulmonary edema. During hospitalization, 1 patient developed early ST within the first 24 hours (acute ST), manifested as unstable angina, which was successfully treated with urgent percutaneous coronary intervention (PCI) by using a thrombus aspiration device and balloon angioplasty of the previously implanted stents. Another patient had subacute ST after 4 days while hospitalized with expression of a non-Q-wave AMI; this patient was treated with primary PCI with a new DES implantation. Two patients suffered sudden death at 16 and 19 days, respectively, after the procedure; these were recorded as secondary to probable ST. One patient had subacute ST after hospital discharge (6 days) secondary to the dual-antiplatelet therapy discontinuation, with development of non-Q-wave AMI; this was treated with primary PCI with balloon angioplasty. Overall, ST occurred in 5 patients (4.8 %); all were early ST, and 3 were definite (2.9%) with angiographic confirmation. All ST cases received noncompliant balloon post dilatation and IVUS during the procedure, with good immediate results. The 99 patients who survived the 30-day post-procedure follow up were monitored clinically for a median of 15 months (range, 1–54). The incidence of cumulative MACE during follow up was 12.7%. Two deaths occurred during follow up: 1 patient died due to STEMI, which was in a different location from the artery treated by RA in the procedure, and another patient died in the postoperative period following coronary artery bypass grafting (CABG). This patient had severe LMCA stent restenosis after 9 months of follow up. One patient presented with a non-Q-wave AMI at 2-month follow up which was unrelated to the artery treated during the procedure. A total of 5 patients underwent TLR due to in-stent restenosis: 1 was referred for CABG due to LMCA in-stent restenosis (this is the patient who died, as described above). The remaining 4 underwent PCI with a different type of DES. There were no deaths from non-cardiac causes during the follow-up period. The mean duration of dual-antiplatelet therapy was 10.78 months (range, 6.0–52.0).

Discussion

In the field of interventional cardiology, the treatment of severely calcified coronary lesions involves a series of technical difficulties that may influence the final success of the procedure. This study shows the results of RA followed by DES implantation in a nonselected series of patients with severely calcified coronary lesions. In spite of the unfavorable angiographic profile of the patients (68.6% of cases had type C lesions, 46.1% had 3-vessel disease, and 12.7% had LMCA lesions), we found a 97% immediate procedural success rate in our series. When we analyzed the success in the first month after the treatment, it was 94%. Both percentages are similar to those published for RA followed by DES implantation.^13–17 In our series, 50% of patients were > 70 years of age, 52.9% were diabetics and 12.7% had chronic kidney disease. Despite this unfavorable clinical profile, the total cardiac deaths and in-hospital cardiac deaths were 4.9% and 0.9%, respectively, at a median of 15 months of follow up (range, 1–54 months). Clavijo et al,¹³ in a series of 81 patients with RA followed by sirolimus-eluting stent implantation and a 6-month median follow up, reported a death rate of 6.8%, with no in-hospital deaths. The mean age in the series was 71.5 ± 9.6 years, 44.4% were diabetics and 83.6% had type C lesions. More recently, Furuichi et al,¹⁴ in a series of 96 patients with de novo severely calcified coronary lesions and a mean age of 68 ± 9 years, found a cardiac death rate of 4.2%. In our series, we found a TLR rate of 8.8%. This is substantially better than that initially published by Reifart et al¹⁸ for simple balloon angioplasty before the stent era in which there were extremely high rates of restenosis and thus TLR exceeding 40%. The TLR rate for RA followed by BMS reported by Moussa et al⁵ was 18%, with a 22.5% restenosis rate and 93.4% procedural success. Likewise, other studies with BMS have shown good immediate results, but high TLR rates of 16–25% during follow up.^6,7,19 Different studies have reported several TLR rates with DES following RA. Clavijo et al¹³ reported a TLR rate of 4.2% at 6 months. In that series, the number of diabetics was lower (44.4%, compared to 52.9% in our study) and the total length of stent implanted was shorter (24.4 ± 6.27 mm, compared to 39.3 ± 19.8 mm in our study). The study by Khattab et al,¹⁵ with only 27 patients, describes a TLR rate of 7.4% within a 9-month follow-up period. Furuichi et al¹⁴ obtained a TLR rate of 9.5% during a mean follow-up period of 14.7 months, with a lower percentage of diabetics (30.5%) as well as of patients with chronic renal disease (7.4%), although with a greater total stent length (48.4 ± 24.9 mm) and with a greater treatment ratio of bifurcated lesions (24%). Garcia de Lara et al,¹⁶ in a series of 50 consecutive patients with severely calcified lesions treated with RA followed by a paclitaxel-eluting stent, obtained a TLR rate of 6% after 1 year. The average age of their patients was 70 ± 1.2 years, 75% were diabetics and the total average stent length was 41 ± 4 mm. Most recently, in a very interesting study, Rathore et al,¹⁷ in a series of 516 patients, of whom 391 were treated with DES following RA with angiographic follow up in 360 patients (70%), showed a restenosis rate of 11% and a TLR rate of 10.6% in the DES group (significantly lower than the BMS group), which are slightly higher than our own rates. They established ostial lesion location, chronic total occlusion lesions and the use of BMS as independent predictors of restenosis in their series. The incidence of cumulative MACE was 12.75% in our series, which is similar to the 11% published by Clavijo et al¹³ and lower than the 15.8% reported by Furuichi et al.¹⁴ There were 3 cases of definite ST (2.9%), all of which were early ST (1 acute and 2 subacute). If we add the 2 patients with sudden death as probable, the total rate becomes 4.8%. Furuichi et al¹⁴ described a definite ST rate of 2.1%, and if they added those considered as possible, the total rate would be 4.2%. This rate may be relatively high compared to those obtained with simpler patients and lesions.²⁰ However, in a series of patients with unfavorable clinical and angiographic profiles, this may be justified. Both stent underexpansion and total stent length have been reported as independent factors for DES thrombosis.²¹ Therefore, adequate calcified lesion preparation before stent implantation, especially in long stents, remains an essential component to prevent DES thrombosis. Premature discontinuation of dual-antiplatelet therapy, especially the interruption of clopidogrel intake, is a clear ST risk factor that is constantly repeated in the studies published.^22,23 In our series, 1 of the cases of subacute ST occurred after stopping dual-antiplatelet therapy. Study limitations. This is an observational, nonrandomized study based on the experience of a single center, without a control group. Treatment assignment was ad hoc. A control group in this clinical subset might not be possible because the heavily calcified lesions that cannot be treated without RA could not have successful stenting. The physicians were not blind to the DES types (which could have different outcomes depending on the specific drug). The variability of the procedures and the lack of angiographic follow up could have biased the outcomes.

Conclusion

The combined approach of DES following RA for heavily calcified coronary lesions, which are considered complex lesions, is safe, with a high procedural success rate, and provides good long-term clinical outcomes, with a low rate of MACE in this clinical context.

References

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———————————————————— From the Department of Cardiology, Hospital Universitario Virgen del Rocio, Seville, Spain. The authors report no conflicts of interest regarding the content herein. Manuscript submitted August 3, 2010, provisional acceptance given September 7, 2010, final version accepted October 25, 2010. Address for correspondence: Javier Benezet, MD, Department of Cardiology, Hospital Universitario Virgen del Rocio. Avenida Manuel Siurot s/n. 41013 Seville, Spain. E-mail: javbenezet@hotmail.com