Abstract: Background. The optimal technique for lesion preparation in heavily calcified coronary lesions (HCCL) prior to drug-eluting stent (DES) implantation has not been described. The aim of this study was to compare the clinical outcomes of lesion preparation with rotational atherectomy (ROTA), plain old balloon angioplasty (POBA), or cutting-balloon angioplasty (CBA) in patients with HCCL who were treated with DES. Methods. The study cohort comprised 737 consecutive patients (874 lesions) who underwent RA (n = 264), POBA (n = 220), or CBA (n = 253) for HCCL at our institution and were treated with DES. Patients with mild or moderate calcified lesions, restenotic lesions, treatment with bare-metal stent (BMS), or history of prior coronary artery bypass graft (CABG) were excluded. The analyzed clinical parameters were the 1-month, 6-month, and 12-month rates of death (all-cause and cardiac), Q-wave myocardial infarction (MI), target-lesion revascularization (TLR), definite stent thrombosis (ST), and major adverse cardiac event (MACE), defined as the composite of death, Q-wave MI, or TLR. Results. The patients were well matched for their baseline characteristics except for age (RA = 71.9 ± 10.4 years; POBA = 68.0 ± 10.8 years; CBA = 68.7 ± 11.8 years; P<.001) and hypertension (RA = 90.9%; POBA = 80.9%; CBA = 84.2%; P=.01), which were different among the three cohorts. The three cohorts had similar clinical outcomes at both short-term and long-term follow-up. The 12-month results were all-cause death (RA = 9.8%l POBA = 8.2%; CBA = 4.5%; P=.18), cardiac death (RA = 3.1%; POBA = 2.5%; CBA = 1.3%; P=.61), Q-wave MI (RA = 0%; POBA = 0%; CBA = 0.7%; P>.99), TLR (RA = 5.2%; POBA = 3.5%; CBA = 3.9%; P=.76), ST (RA = 0%; POBA = 0%; CBA = 0.6%; P=.63) and MACE (RA = 14.6%; POBA = 12.3%; CBA = 8.3%; P=.20). The 1-year MACE-free survival rates were also similar among the three cohorts (log-rank P=.20). Conclusion. A strategy of lesion preparation with RA, POBA, or CBA in HCCL may be associated with similar clinical outcomes in patients undergoing percutaneous intervention with DES. The RA group had a trend toward greater MACE, death, and TLR.
J INVASIVE CARDIOL 2015;27(9):387-391
Key words: stent thrombosis, percutaneous coronary intervention, restenosis
Percutaneous coronary intervention (PCI) for heavily calcified coronary lesions (HCCL) is associated with increased procedural risk and poorer clinical outcomes.1,2 Adequate lesion preparation prior to stent implantation is essential to ensure stent deliverability, stent expansion, and apposition against the vessel wall.3 Three standard methods are currently used in lesion preparation for HCCL: rotational atherectomy (RA), plain old balloon angioplasty (POBA), and cutting-balloon angioplasty (CBA). The optimal technique for lesion preparation in HCCL prior to drug-eluting stent (DES) implantation has not been described. The aim of this study was therefore to compare the clinical outcomes of these three different lesion preparation strategies in patients with HCCL who were treated with DES.
This single-center, retrospective study comprised 737 consecutive patients (874 lesions) who had undergone RA (264 patients; 320 lesions), POBA (220 patients; 290 lesions), or CBA (253 patients; 264 lesions) for HCCL prior to DES implantation at the MedStar Washington Hospital Center from October 2003 to January 2013. Heavily calcified coronary lesions were defined visually as the presence of calcium before contrast injection at the site of the lesion and involving both sides of the vessel wall by a senior attending interventional cardiologist blinded to the treatment arm. Patients with ST-elevation myocardial infarction (STEMI), mild or moderate calcified lesions, restenotic lesions, treatment with a bare-metal stent (BMS), or a history of prior CABG were excluded. All patients provided written informed consent. The study complied with the Declaration of Helsinki for investigation in human beings and was approved by the institutional ethics committee of the Medstar Washington Hospital Center. RA (Rotablator system; Boston Scientific-Scimed Corporation) was performed according to standard practice. In all cases, the interventional strategy, as well as the use of adjunctive devices and pharmacotherapy, was at the discretion of the operating interventional cardiologist. All patients received aspirin 325 mg before the procedure and were recommended to continue this regime indefinitely. In addition, clopidogrel 75 mg daily following a 300 mg or 600 mg loading dose was commenced preprocedurally and continued for 12 months. Follow-up data at 1 month, 6 months, and 12 months were obtained by telephone contact, mailed questionnaire, or outpatient review.
The analyzed clinical parameters were the 1-month, 6-month, and 12-month rates of death, Q-wave myocardial infarction (MI), target-lesion revascularization (TLR), definite stent thrombosis (ST), and major adverse cardiac event (MACE), defined as the composite of death, Q-wave MI, or TLR.
Heavily calcified coronary lesions were defined visually as the presence of calcium before contrast injection at the site of the lesion and involving both sides of the vessel wall by a senior attending interventional cardiologist blinded to the treatment arm. Q-wave MI was defined as evidence of new Q-waves on the electrocardiogram at the time of MI, with the latter defined as a total creatinine kinase increase ≥2x the upper limit of normal and/or creatinine kinase (MB fraction) ≥20 ng/mL together with symptoms and/or ischemic electrocardiographic changes. Hypercholesterolemia was defined as fasting cholesterol >250 mg/dL or the use of lipid lowering therapy. Systemic hypertension was defined as blood pressure >140/90 mm Hg or the use of antihypertensive therapy. Renal impairment was defined as serum creatinine >1.2 mg/dL. Congestive heart failure was defined as evidence of fluid retention due to cardiac causes prior to admission. Angiographic success was defined as postprocedural stenosis ≤30% and Thrombolysis in Myocardial Infarction (TIMI) flow grade 3. TLR was defined as ischemia-driven percutaneous or surgical repeat intervention in the stent or within 5 mm proximal or distal to the stent. ST was classified in accordance with the Academic Research Consortium definitions as definite, probable, or possible.
Data were analyzed using the Statistical Analysis System version 9.3 (SAS Institute). Continuous variables are expressed as mean ± standard deviation and analyzed using analysis of variance (ANOVA). Categorical variables are displayed as percentages and analyzed by Chi-square or Fisher’s exact test. A P-value <.05 was considered significant. One-year event-free survival curves were constructed with Kaplan-Meier curves.
The baseline characteristics and procedural indications of the patients are summarized in Table 1. The patients were well matched for their baseline characteristics except for age (RA = 71.9 ± 10.4 years; POBA = 68.0 ± 10.8 years; CBA = 68.7 ± 11.8; P<.001) and hypertension (RA = 90.9%; POBA = 80.9%; CBA = 84.2%; P=.01), which were different among the three cohorts.
The lesion and procedural characteristics are summarized in Table 2. The three cohorts differed in the target lesion (right coronary artery: RA = 29.4%; POBA = 23.1%; CBA = 20.8% [P=.04] and left circumflex artery: RA = 13.7%; POBA = 21.7%; CBA = 20.1% [P=.04]), use of intravascular ultrasound (RA = 79.3%; POBA = 55.4%; CBA = 89%; P<.001), stent number (RA = 1.7 ± 1.0; POBA = 1.5 ± 0.9; CBA = 1.4 ± 0.9; P=.01), stent length (RA = 20.3 ± 6.3 mm, POBA = 20.0 ± 6.4 mm; CBA = 18.6 ± 6.6 mm; P=.01), and procedural time (RA = 88.2 ± 41.1 minutes; POBA = 64.6 ± 30.0 minutes; CBA = 75.2 ± 53.5 minutes; P<.001). There was a trend for greater stent diameter in the RA and CBA groups as compared with the POBA group (RA = 3.0 ± 0.6; POBA = 2.9 ± 0.3; CBA = 3.0 ± 0.4; P=.06).
The analyzed clinical parameters at 1 month, 6 months, and 12 months are summarized in Table 3. The three cohorts had similar clinical outcomes at both short-term and long-term follow-up. The 12-month results were all-cause death (RA = 9.8%; POBA = 8.2%; CBA = 4.5%; P=.18), cardiac death (RA = 3.1%; POBA = 2.5%; CBA = 1.3%; P=.61), Q-wave MI (RA = 0%; POBA = 0%; CBA = 0.7%; P>.99), TLR (RA = 5.2%; POBA = 3.5%; CBA = 3.9%; P=.76), ST (RA = 0%; POBA = 0%; CBA = 0.6%; P=.63) and MACE (RA = 14.6%; POBA = 12.3%; CBA = 8.3%; P=.20). The 1-year MACE-free survival rates were also similar among the three cohorts (log-rank P=.20) (Figure 1).
The main finding of this study is that in patients with HCCL requiring DES implantation, a strategy of lesion preparation with RA, POBA, or CBA may be associated with similar clinical outcomes at short-term and long-term follow-up. The RA group was associated with a numerically greater rate of MACE, death, and TLR as compared with the POBA group.
The mechanism of lumen gain with RA, POBA, and CBA is different. RA uses a diamond burr to pulverize calcific plaques into microparticles and obtain an enlarged, smooth lumen.4 RA is also associated with prolonged procedural time and cannot be used in small vessels or severely tortuous vessels due to the risk of coronary perforation. POBA, in contrast, compresses the plaque both longitudinally and circumferentially, while CBA creates longitudinal incisions along the plaque, thus enabling plaque expansion. Such differences may be associated with differing mechanisms of vessel remodeling that could translate into differences in clinical outcomes.
Although DES implantation has been associated with reduced restenosis rates in landmark clinical studies, patients with calcific lesions have often been excluded from such trials.5-7 HCCL may impose a special threat to DESs, arising from damage to the polymer/drug coating as well as suboptimal drug elution into the vessel wall from the extensive calcification.8 Analysis of data from the National Heart, Lung, and Blood Institute Dynamic Registry of 1537 patients with moderate to severe calcified coronary lesions that were treated with either a BMS or a DES has confirmed the safety and efficacy of DES implantation in such lesions.9 As compared with BMS, the use of DES was associated with a significant reduction in the risk of repeat revascularization (10% vs 15.3%; P=.01) at 1-year follow-up with no differences in the risk of death and MI. Further support for the efficacy of DES in calcific coronary lesions has been provided by the 2-year angiographic and 3-year clinical follow-up results of the SPIRIT II study.10
The optimal method for lesion preparation in HCCL prior to DES implantation has not been clearly defined. The ROTAXUS (Rotational Atherectomy Prior to Taxus Stent Treatment for Complex Native Coronary Artery Disease) trial of 240 patients randomized to either RA and stenting or balloon predilatation and stenting demonstrated greater late lumen loss with RA and similar rates of in-stent restenosis (11.4% vs 10.6%; P>.99), MACE (24.2% vs 28.3%; P=.46), and TLR (11.7% vs 12.5%; P=.84).11 ROTAXUS thus recommended balloon predilatation with provisional rotablation as the default strategy for HCCL. Vaquerizo et al compared plaque modification with either CBA and/or RA prior to DES implantation in a cohort of 145 consecutive patients with calcific coronary lesions.12 In their cohort, CBA and RA were associated with similar rates of death, Q-wave MI, non-Q wave MI, ST, and MACE at 15 ± 11 months.
Although a strategy of lesion preparation comparing RA, POBA, or CBA prior to stenting has not been previously examined, the data presented appear to indicate that they may produce similar clinical outcomes. There are several potential explanations for such an observation. First, data from ROTAXUS indicate that the in-stent late lumen loss associated with the POBA arm (0.31 mm) was lower than the various TAXUS trials,13-15 while the in-stent late lumen loss associated with the ROTA arm (0.44 mm) was higher than anticipated despite greater postprocedural luminal diameter. This observation may be related in part to the relatively high inflation pressures that are used to predilate calcific lesions as well as to the increased neointimal growth that has been associated with RA, which has accounted for the increased restenosis rate observed in the pre-DES era.16-18
Second, the use of intravascular ultrasound in our study was relatively high, at 74.4% for the entire cohort. This has enabled optimal stent expansion and apposition, which have been shown to be associated with favorable clinical and angiographic outcomes in patients undergoing PCI.19,20 Finally, the relatively high proportion of patients in our study (46.6% overall) receiving second-generation DESs, which have thinner stent struts and more biocompatible polymers, may have mitigated any small differences that could have arisen from the use of different lesion preparation techniques.
Study limitations. Clinical registries are helpful complements to randomized studies, as they provide clinical information in a broader patient population. However, registries suffer from well-established limitations and our study is no exception. Statistical methods were used to adjust for baseline differences, but the possibility of unmeasured confounders can never be excluded. Differences in individual practice patterns, such as the use of different DES types and intravascular ultrasound in some patients and not in others could have impacted our results. The decision to use RA, POBA, or CBA was solely based on the operator’s discretion. However, an inherent bias to choose one technique over another cannot be excluded. The number of crossovers from one treatment arm to another has not been recorded and this may have impacted our results. Finally, HCCLs were adjudicated on the basis of angiographic data rather than intravascular ultrasound and this may have led to imprecisions in patient enrollment.
In patients presenting with HCCL and undergoing PCI with DES, a strategy of lesion preparation with RA, POBA, or CBA may be associated with similar clinical outcomes in both short-term and long-term follow-up. The RA group was associated with a numerically greater rate of MACE, death, and TLR as compared with the POBA group.
- Nishida K, Kimura T, Kawai K, et al. Comparison of outcomes using the sirolimus-eluting stent in calcified versus non-calcified native coronary lesions in patients on- versus not on-chronic hemodialysis (from the j-Cypher registry). Am J Cardiol. 2013;112:647-655.
- Rathore S, Terashima M, Katoh O, et al. Predictors of angiographic restenosis after drug-eluting stents in the coronary arteries: contemporary practice in real-world patients. EuroIntervention. 2009;5:349-354.
- Fujii K, Carlier SG, Mintz GS, et al. Stent underexpansion and residual reference segment stenosis are related to stent thrombosis after sirolimus-eluting stent implantation: an intravascular ultrasound study. J Am Coll Cardiol. 2005;45:995-998.
- Mintz GS, Potkin BN, Keren G, et al. Intravascular ultrasound evaluation of the effect of rotational atherectomy in obstructive atherosclerotic coronary artery disease. Circulation. 1992;86:1383-1393.
- Rathore S, Matsuo H, Terashima M, et al. Rotational atherectomy for fibro-calcific coronary artery disease in drug eluting stent era: procedural outcomes and angiographic follow-up results. Catheter Cardiovasc Interv. 2010;75:919-927.
- Moses JW, Leon MB, Popma JJ, et al. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med. 2003;349:1315-1323.
- Stone GW, Ellis SG, Cox DA, et al. A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease. N Engl J Med. 2004;350:221-231.
- Hodgson JM, Stone GW, Lincoff AM, et al. Late stent thrombosis: considerations and practical advice for the use of drug-eluting stents: a report from the Society for Cardiovascular Angiography and Interventions drug-eluting stent task force. Catheter Cardiovasc Interv. 2007;69:327-333.
- Bangalore S, Vlachos HA, Selzer F, et al. Percutaneous coronary intervention of moderate to severe calcified coronary lesions: insights from the National Heart, Lung, and Blood Institute dynamic registry. Catheter Cardiovasc Interv. 2011;77:22-28.
- Onuma Y, Tanimoto S, Ruygrok P, et al. Efficacy of everolimus eluting stent implantation in patients with calcified coronary culprit lesions: two-year angiographic and three-year clinical results from the SPIRIT II study. Catheter Cardiovasc Interv. 2010;76:634-642.
- Abdel-Wahab M, Richardt G, Joachim Büttner H, et al. High-speed rotational atherectomy before paclitaxel-eluting stent implantation in complex calcified coronary lesions: the randomized ROTAXUS (Rotational Atherectomy Prior to Taxus Stent Treatment for Complex Native Coronary Artery Disease) trial. JACC Cardiovasc Interv. 2013;6:10-19.
- Vaquerizo B, Serra A, Miranda F, et al. Aggressive plaque modification with rotational atherectomy and/or cutting balloon before drug-eluting stent implantation for the treatment of calcified coronary lesions. J Interv Cardiol. 2010;23:240-248.
- Grube E, Silber S, Hauptmann KE, et al. Taxus I: six and twelve-month results from a randomized, double-blind trial on a slow-release paclitaxel-eluting stent for de novo coronary lesions. Circulation. 2003;107:38-42.
- Colombo A, Drzewiecki J, Banning A, et al; for the Taxus II Study Group. Randomized study to assess the effectiveness of slow- and moderate-release polymer-based paclitaxel-eluting stents for coronary artery lesions. Circulation. 2003;108:788-794.
- Stone GW, Ellis SG, Cox DA, et al; for the Taxus IV Investigators. One-year clinical results with the slow-release, polymer-based, paclitaxel-eluting TAXUS stent: the TAXUS-IV trial. Circulation. 2004;109:1942-1947.
- Moussa I, Di Mario C, Mosses J, et al. Coronary stenting after rotational atherectomy in calcified and complex lesions: angiographic and clinical follow-up results. Circulation. 1997;96:128-136.
- Reifart N, Vandormael M, Krajcar M, et al. Randomized comparison of angioplasty of complex coronary lesions at a single center. Excimer laser, rotational atherectomy, and balloon angioplasty comparison study. Circulation. 1997;96:91-98.
- Dill T, Dietz U, Hamm CW, et al. A randomized comparison of balloon angioplasty versus rotational atherectomy in complex coronary lesions (COBRA study). Eur Heart J. 2000;21:1759-1766.
- Claessen BE, Mehran R, Mintz GS, et al. Impact of intravascular ultrasound imaging on early and late clinical outcomes following percutaneous coronary intervention with drug-eluting stents. JACC Cardiovasc Interv. 2011;4:974-981.
- Roy P, Steinberg DH, Sushinsky SJ, et al. The potential clinical utility of intravascular ultrasound guidance in patients undergoing percutaneous coronary intervention with drug-eluting stents. Eur Heart J. 2008;29:1851-1857.
From 1Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC; and 2University of Surrey, Surrey, United Kingdom.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Waksman reports personal fees from Biotronik, Medtronic, AstraZeneca, Boston Scientific, Biosensors International, Abbott Vascular; grants from AstraZeneca, Boston Scientific, Biosensors International, The Medicines Company, Edwards Lifesciences. The remaining authors report no conflicts of interest regarding the content herein.
Manuscript submitted September 2, 2014, provisional acceptance given September 26, 2014, final version accepted April 23, 2015.
Address for correspondence: Ron Waksman, MD, MedStar Washington Hospital Center, 110 Irving Street, NW, Suite 4B-1, Washington DC 20010. Email: firstname.lastname@example.org