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Orbital Atherectomy for Treating De Novo Severely Calcified Coronary Narrowing (1-Year Results from the Pivotal ORBIT II Trial)

2015; Elsevier BV; Volume: 115; Issue: 12 Linguagem: Inglês

10.1016/j.amjcard.2015.03.009

1879-1913

Philippe Généreux, Arthur C. Lee, Christopher Y. Kim, Michael S. Lee, Richard Shlofmitz, Jeffrey W. Moses, Gregg W. Stone, Jeff W. Chambers,

Cardiac Imaging and Diagnostics

Percutaneous coronary intervention of severely calcified lesions has historically been associated with major adverse cardiac event (MACE) rates as high as 30%. In the ORBIT II (Evaluate the Safety and Efficacy of OAS in Treating Severely Calcified Coronary Lesions) trial, treatment of de novo severely calcified lesions with the Diamondback 360° Coronary Orbital Atherectomy System (OAS) resulted in low rates of procedural and 30-day adverse ischemic events. The long-term results from this trial have not been reported. We sought to determine the 1-year outcomes after orbital atherectomy of severely calcified coronary lesions. ORBIT II was a single-arm trial enrolling 443 subjects at 49 US sites with severely calcified lesions usually excluded from randomized trials. OAS utilizes a centrifugal differential sanding mechanism of action for plaque modification prior to stent implantation. After OAS drug-eluting stents were implanted in 88.2% of the patients. The primary safety end point was 30-day MACE, the composite of cardiac death, myocardial infarction, or target vessel revascularization [TVR]. The present analysis reports the 1-year follow-up results from ORBIT II. One-year data were available in 433 of 443 patients (97.7%), with median follow-up time of 16.7 months. The 1-year MACE rate was 16.4%, including cardiac death (3.0%), myocardial infarction (9.7%), and target vessel revascularization (5.9%). The 1-year target lesion revascularization rate was 4.7%, and stent thrombosis occurred in 1 patient (0.2%). Independent predictors of 1-year MACE and target vessel revascularization were diameter stenosis at baseline and the use of bare-metal stents. In patients with severely calcified lesions who underwent percutaneous coronary intervention, the use of OAS was associated with low rates of 1-year adverse ischemic events compared with historical controls. This finding has important clinical implications for the selection of optimum treatment strategies for patients with severely calcified lesions. Percutaneous coronary intervention of severely calcified lesions has historically been associated with major adverse cardiac event (MACE) rates as high as 30%. In the ORBIT II (Evaluate the Safety and Efficacy of OAS in Treating Severely Calcified Coronary Lesions) trial, treatment of de novo severely calcified lesions with the Diamondback 360° Coronary Orbital Atherectomy System (OAS) resulted in low rates of procedural and 30-day adverse ischemic events. The long-term results from this trial have not been reported. We sought to determine the 1-year outcomes after orbital atherectomy of severely calcified coronary lesions. ORBIT II was a single-arm trial enrolling 443 subjects at 49 US sites with severely calcified lesions usually excluded from randomized trials. OAS utilizes a centrifugal differential sanding mechanism of action for plaque modification prior to stent implantation. After OAS drug-eluting stents were implanted in 88.2% of the patients. The primary safety end point was 30-day MACE, the composite of cardiac death, myocardial infarction, or target vessel revascularization [TVR]. The present analysis reports the 1-year follow-up results from ORBIT II. One-year data were available in 433 of 443 patients (97.7%), with median follow-up time of 16.7 months. The 1-year MACE rate was 16.4%, including cardiac death (3.0%), myocardial infarction (9.7%), and target vessel revascularization (5.9%). The 1-year target lesion revascularization rate was 4.7%, and stent thrombosis occurred in 1 patient (0.2%). Independent predictors of 1-year MACE and target vessel revascularization were diameter stenosis at baseline and the use of bare-metal stents. In patients with severely calcified lesions who underwent percutaneous coronary intervention, the use of OAS was associated with low rates of 1-year adverse ischemic events compared with historical controls. This finding has important clinical implications for the selection of optimum treatment strategies for patients with severely calcified lesions. Despite advances in technology, percutaneous coronary intervention (PCI) of severely calcified coronary lesions remains a challenge. Contemporary studies have shown that the presence of moderate or severe coronary calcification at the target lesion is associated with a substantial increase in death, myocardial infarction (MI), stent thrombosis, and need for revascularization.1Genereux P. Madhavan M.V. Mintz G.S. Maehara A. Palmerini T. Lasalle L. Xu K. McAndrew T. Kirtane A. Lansky A.J. Brener S.J. Mehran R. Stone G.W. Ischemic outcomes after coronary intervention of calcified vessels in acute coronary syndromes. Pooled analysis from the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) and ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) Trials.J Am Coll Cardiol. 2014; 63: 1845-1854Crossref PubMed Scopus (299) Google Scholar, 2Bangalore S. Vlachos H.A. Selzer F. Wilensky R.L. Kip K.E. Williams D.O. Faxon D.P. 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: 22-28Crossref PubMed Scopus (74) Google Scholar, 3Bourantas C.V. Zhang Y.J. Garg S. Iqbal J. Valgimigli M. Windecker S. Mohr F.W. Silber S. Vries T. Onuma Y. Garcia-Garcia H.M. Morel M.A. Serruys P.W. Prognostic implications of coronary calcification in patients with obstructive coronary artery disease treated by percutaneous coronary intervention: a patient-level pooled analysis of 7 contemporary stent trials.Heart. 2014; 100: 1158-1164Crossref PubMed Scopus (183) Google Scholar, 4Xu Y. Mintz G.S. Tam A. McPherson J.A. Iniguez A. Fajadet J. Fahy M. Weisz G. De Bruyne B. Serruys P.W. Stone G.W. Maehara A. Prevalence, distribution, predictors, and outcomes of patients with calcified nodules in native coronary arteries: a 3-vessel intravascular ultrasound analysis from Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT).Circulation. 2012; 126: 537-545Crossref PubMed Scopus (96) Google Scholar, 5Madhavan M.V. Tarigopula M. Mintz G.S. Maehara A. Stone G.W. Genereux P. Coronary artery calcification: pathogenesis and prognostic implications.J Am Coll Cardiol. 2014; 63: 1703-1714Crossref PubMed Scopus (321) Google Scholar, 6Moussa I. Ellis S.G. Jones M. Kereiakes D.J. McMartin D. Rutherford B. Mehran R. Collins M. Leon M.B. Popma J.J. Russell M.E. Stone G.W. Impact of coronary culprit lesion calcium in patients undergoing paclitaxel-eluting stent implantation (a TAXUS-IV substudy).Am J Cardiol. 2005; 96: 1242-1247Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar Coronary calcification is frequent, with about 1/3 of the lesions treated by PCI presenting with a substantial amount of calcification angiographically.1Genereux P. Madhavan M.V. Mintz G.S. Maehara A. Palmerini T. Lasalle L. Xu K. McAndrew T. Kirtane A. Lansky A.J. Brener S.J. Mehran R. Stone G.W. Ischemic outcomes after coronary intervention of calcified vessels in acute coronary syndromes. Pooled analysis from the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) and ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) Trials.J Am Coll Cardiol. 2014; 63: 1845-1854Crossref PubMed Scopus (299) Google Scholar Current therapeutic options to manage calcified lesions (e.g., cutting/scoring balloons and rotational atherectomy) are associated with a high rate of restenosis and stent failure at long-term follow-up.5Madhavan M.V. Tarigopula M. Mintz G.S. Maehara A. Stone G.W. Genereux P. Coronary artery calcification: pathogenesis and prognostic implications.J Am Coll Cardiol. 2014; 63: 1703-1714Crossref PubMed Scopus (321) Google Scholar Recently, the ORBIT II (Evaluate the Safety and Efficacy of OAS in Treating Severely Calcified Coronary Lesions) trial demonstrated favorable procedural and 30-day outcomes with the Diamondback 360° Coronary Orbital Atherectomy System (OAS) (Cardiovascular Systems, Inc., St. Paul, Minnesota) in the treatment of severely calcified lesions, resulting in its Food and Drug Administration (FDA) approval.7Chambers J.W. Feldman R.L. Himmelstein S.I. Bhatheja R. Villa A.E. Strickman N.E. Shlofmitz R.A. Dulas D.D. Arab D. Khanna P.K. Lee A.C. Ghali M.G. Shah R.R. Davis T.P. Kim C.Y. Tai Z. Patel K.C. Puma J.A. Makam P. Bertolet B.D. Nseir G.Y. Pivotal trial to evaluate the safety and efficacy of the orbital atherectomy system in treating de novo, severely calcified coronary lesions (ORBIT II).JACC Cardiovasc Interv. 2014; 7: 510-518Crossref PubMed Scopus (216) Google Scholar Whether the beneficial effects of this device seen at 30 days translate into favorable 1-year outcomes is not known. We report the prespecified analysis of the 1-year outcomes from the ORBIT II pivotal trial. The design and initial results of ORBIT II have been published previously.7Chambers J.W. Feldman R.L. Himmelstein S.I. Bhatheja R. Villa A.E. Strickman N.E. Shlofmitz R.A. Dulas D.D. Arab D. Khanna P.K. Lee A.C. Ghali M.G. Shah R.R. Davis T.P. Kim C.Y. Tai Z. Patel K.C. Puma J.A. Makam P. Bertolet B.D. Nseir G.Y. Pivotal trial to evaluate the safety and efficacy of the orbital atherectomy system in treating de novo, severely calcified coronary lesions (ORBIT II).JACC Cardiovasc Interv. 2014; 7: 510-518Crossref PubMed Scopus (216) Google Scholar In brief, ORBIT II was a prospective, multicenter, nonblinded, single-arm clinical trial that enrolled patients with de novo severely calcified coronary lesions who underwent PCI. Key study inclusion criteria included: (1) target vessel reference diameter ≥2.5 and ≤4.0 mm with a stenosis ≥70% and <100% or a stenosis ≥50% and 30 days before with no >30% in-stent restenosis; (2) recent MI (defined as creatine kinase-MB [CK-MB] >1× upper limit of laboratory normal [ULN] within 30 days of the index procedure); and (3) evidence of current left ventricular ejection fraction ≤25%. The ORBIT II trial conformed to ethical guidelines of the Declaration of Helsinki, and study participants provided informed consent. The coronary OAS uses a diamond-coated eccentric crown that, while rotating over an atherectomy guide wire, expands laterally through centrifugal force (up to a maximum orbit diameter for a given rotational speed) resulting in a differential sanding of coronary calcification. Two OAS configurations were used in the ORBIT II trial, pneumatic OAS and electric OAS, with crown diameter ranging from 1.25 up to 2.00 mm. Detailed description of OAS mechanism of action can be found elsewhere.8Parikh K. Chandra P. Choksi N. Khanna P. Chambers J. Safety and feasibility of orbital atherectomy for the treatment of calcified coronary lesions: the ORBIT I trial.Catheter Cardiovasc Interv. 2013; 81: 1134-1139Crossref PubMed Scopus (93) Google Scholar, 9Bhatt P. Parikh P. Patel A. Chag M. Chandarana A. Parikh R. Parikh K. Orbital atherectomy system in treating calcified coronary lesions: 3-year follow-up in first human use study (ORBIT I trial).Cardiovasc Revasc Med. 2014; 15: 204-208Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar The use of other adjunctive devices, such as thrombectomy, embolic protection devices, brachytherapy, or cutting balloons, was not allowed. Pre- and postprocedure dual antiplatelet therapy was recommended to conform to the American Heart Association/American College of Cardiology/Society for Cardiovascular Angiography and Interventions joint guidelines for PCI.10Levine G.N. Bates E.R. Blankenship J.C. Bailey S.R. Bittl J.A. Cercek B. Chambers C.E. Ellis S.G. Guyton R.A. Hollenberg S.M. Khot U.N. Lange R.A. Mauri L. Mehran R. Moussa I.D. Mukherjee D. Nallamothu B.K. Ting H.H. American College of Cardiology FoundationAmerican Heart Association Task Force on Practice GuidelinesSociety for Cardiovascular Angiography and Interventions2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions.J Am Coll Cardiol. 2011; 58: e44-e122Abstract Full Text Full Text PDF PubMed Scopus (1975) Google Scholar The primary safety end point of ORBIT II was the rate of 30-day major adverse cardiac events (MACEs) defined as the composite of cardiac death, MI, and target vessel revascularization (TVR). MI was defined as CK-MB >3x ULN with or without new pathologic Q waves. Rate of stent thrombosis was reported and defined according to the Academic Research Consortium definition.11Cutlip D.E. Windecker S. Mehran R. Boam A. Cohen D.J. van Es G.A. Steg P.G. Morel M.A. Mauri L. Vranckx P. McFadden E. Lansky A. Hamon M. Krucoff M.W. Serruys P.W. Academic Research ConsortiumClinical end points in coronary stent trials: a case for standardized definitions.Circulation. 2007; 115: 2344-2351Crossref PubMed Scopus (4751) Google Scholar All adverse events were adjudicated by an independent clinical events committee. All patients were followed clinically during the index hospitalization, at 30 days and at 1 year. Continuous variables are summarized as mean ± SD. Survival curves for time-to-event variables were constructed on the basis of all available follow-up data using Kaplan-Meier methods. Multivariable Cox proportional hazards regression was performed to identify independent predictors of 1-year MACE and target vessel revascularization (TVR) (2-sided α = 0.05 for significance). The multivariable model was built with candidate variables being selected if of clinical interest and/or satisfying the criterion of p 1.25 mm crown1.24 (0.50, 3.08)0.641.02 (0.24, 4.34)0.98∗ Current/former smoker versus never smoked. Open table in a new tab The present study describes the long-term impact of treatment of severely calcified lesions using the novel and recently FDA-approved OAS. The main findings of the present study extend the favorable procedural and 30-day results previously reported7Chambers J.W. Feldman R.L. Himmelstein S.I. Bhatheja R. Villa A.E. Strickman N.E. Shlofmitz R.A. Dulas D.D. Arab D. Khanna P.K. Lee A.C. Ghali M.G. Shah R.R. Davis T.P. Kim C.Y. Tai Z. Patel K.C. Puma J.A. Makam P. Bertolet B.D. Nseir G.Y. Pivotal trial to evaluate the safety and efficacy of the orbital atherectomy system in treating de novo, severely calcified coronary lesions (ORBIT II).JACC Cardiovasc Interv. 2014; 7: 510-518Crossref PubMed Scopus (216) Google Scholar and demonstrate a relatively low rate of 1-year adverse ischemic events after treatment of this complex and high-risk cohort with OAS. PCI of calcified lesions have been shown to be associated with a worse prognoses compared with lesions with no calcification.1Genereux P. Madhavan M.V. Mintz G.S. Maehara A. Palmerini T. Lasalle L. Xu K. McAndrew T. Kirtane A. Lansky A.J. Brener S.J. Mehran R. Stone G.W. Ischemic outcomes after coronary intervention of calcified vessels in acute coronary syndromes. Pooled analysis from the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) and ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) Trials.J Am Coll Cardiol. 2014; 63: 1845-1854Crossref PubMed Scopus (299) Google Scholar, 2Bangalore S. Vlachos H.A. Selzer F. Wilensky R.L. Kip K.E. Williams D.O. Faxon D.P. 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: 22-28Crossref PubMed Scopus (74) Google Scholar, 3Bourantas C.V. Zhang Y.J. Garg S. Iqbal J. Valgimigli M. Windecker S. Mohr F.W. Silber S. Vries T. Onuma Y. Garcia-Garcia H.M. Morel M.A. Serruys P.W. Prognostic implications of coronary calcification in patients with obstructive coronary artery disease treated by percutaneous coronary intervention: a patient-level pooled analysis of 7 contemporary stent trials.Heart. 2014; 100: 1158-1164Crossref PubMed Scopus (183) Google Scholar, 5Madhavan M.V. Tarigopula M. Mintz G.S. Maehara A. Stone G.W. Genereux P. Coronary artery calcification: pathogenesis and prognostic implications.J Am Coll Cardiol. 2014; 63: 1703-1714Crossref PubMed Scopus (321) Google Scholar, 6Moussa I. Ellis S.G. Jones M. Kereiakes D.J. McMartin D. Rutherford B. Mehran R. Collins M. Leon M.B. Popma J.J. Russell M.E. Stone G.W. Impact of coronary culprit lesion calcium in patients undergoing paclitaxel-eluting stent implantation (a TAXUS-IV substudy).Am J Cardiol. 2005; 96: 1242-1247Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar Coronary calcification often leads to difficulty in delivering coronary devices, may damage the drug polymer and stent platform,13Kuriyama N. Kobayashi Y. Yamaguchi M. Shibata Y. Usefulness of rotational atherectomy in preventing polymer damage of everolimus-eluting stent in calcified coronary artery.JACC Cardiovasc Interv. 2011; 4: 588-589Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar and limit full stent expansion, resulting in suboptimal procedural results and an increased risk of subsequent ischemic adverse events. Appropriate lesion preparation remains crucial to ensure optimal angiographic and clinical outcomes. However, despite improving procedural success and acute gain, the Rotational Atherectomy Prior to Taxus Stent Treatment for Complex Native Coronary Artery Disease (ROTAXUS) trial failed to demonstrate any clinical benefit of rotational atherectomy compared with standard balloon predilation for preparation of calcified lesions before DES implantation in regard to 9-month TVR (16.7% vs 18.3%, p = 0.73), TLR (11.7% vs 12.5%, p = 0.85), and MACE rates (defined as a composite of death, MI, and TVR; 24.2% vs 28.3%, p = 0.46).14Abdel-Wahab M. Richardt G. Joachim Buttner H. Toelg R. Geist V. Meinertz T. Schofer J. King L. Neumann F.J. Khattab A.A. 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: 10-19Abstract Full Text Full Text PDF PubMed Scopus (344) Google Scholar In contrast, the results with OAS in the present study are encouraging, with lower rates of TVR (5.9%), TLR (4.7%), and cumulative MACE (16.7%) at 1 year compared with historical controls, despite using a more stringent definition of severe coronary calcification as an enrolling criterion. Indeed, >90% of the treated lesions in the ORBIT II trial were considered severely calcified compared with ∼50% of the lesions enrolled in ROTAXUS.14Abdel-Wahab M. Richardt G. Joachim Buttner H. Toelg R. Geist V. Meinertz T. Schofer J. King L. Neumann F.J. Khattab A.A. 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: 10-19Abstract Full Text Full Text PDF PubMed Scopus (344) Google Scholar Similarly, our results compared favorably with the recently published large pooled analysis from the Acute Catheterization and Urgent Intervention Triage Strategy and Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction trials, showing TLR and MACE rates in patients with severe coronary calcification who underwent PCI being 8.7% and 19.9%, respectively.1Genereux P. Madhavan M.V. Mintz G.S. Maehara A. Palmerini T. Lasalle L. Xu K. McAndrew T. Kirtane A. Lansky A.J. Brener S.J. Mehran R. Stone G.W. Ischemic outcomes after coronary intervention of calcified vessels in acute coronary syndromes. Pooled analysis from the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) and ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) Trials.J Am Coll Cardiol. 2014; 63: 1845-1854Crossref PubMed Scopus (299) Google Scholar That being said, ORBIT II was a single-arm trial with no direct comparator, and conclusions from indirect comparisons with different studies (including different patient populations, different stent types, etc.) should be considered hypothesis generating. Given the angiographic complexity and high-risk profile of the ORBIT II population, the 1-year stent thrombosis rate is surprisingly low and compares favorably with previous studies.15Raber L. Magro M. Stefanini G.G. Kalesan B. van Domburg R.T. Onuma Y. Wenaweser P. Daemen J. Meier B. Juni P. Serruys P.W. Windecker S. Very late coronary stent thrombosis of a newer-generation everolimus-eluting stent compared with early-generation drug-eluting stents: a prospective cohort study.Circulation. 2012; 125: 1110-1121Crossref PubMed Scopus (323) Google Scholar, 16Palmerini T. Biondi-Zoccai G. Della Riva D. Mariani A. Sabate M. Smits P.C. Kaiser C. D'Ascenzo F. Frati G. Mancone M. Genereux P. Stone G.W. Clinical outcomes with bioabsorbable polymer- versus durable polymer-based drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis.J Am Coll Cardiol. 2014; 63: 299-307Crossref PubMed Scopus (245) Google Scholar, 17Palmerini T. Biondi-Zoccai G. Della Riva D. Stettler C. Sangiorgi D. D'Ascenzo F. Kimura T. Briguori C. Sabate M. Kim H.S. De Waha A. Kedhi E. Smits P.C. Kaiser C. Sardella G. Marullo A. Kirtane A.J. Leon M.B. Stone G.W. Stent thrombosis with drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis.Lancet. 2012; 379: 1393-1402Abstract Full Text Full Text PDF PubMed Scopus (817) Google Scholar Indeed, only 1 case (0.2%) of stent thrombosis occurred (at day 0, postprocedure). This finding is notable and may represent one of the most beneficial effects of OAS as an optimal tool in lesion preparation for severely calcified lesions. Angiographic lesion complexity and calcification have been identified as independent predictors of stent thrombosis,1Genereux P. Madhavan M.V. Mintz G.S. Maehara A. Palmerini T. Lasalle L. Xu K. McAndrew T. Kirtane A. Lansky A.J. Brener S.J. Mehran R. Stone G.W. Ischemic outcomes after coronary intervention of calcified vessels in acute coronary syndromes. Pooled analysis from the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) and ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) Trials.J Am Coll Cardiol. 2014; 63: 1845-1854Crossref PubMed Scopus (299) Google Scholar, 18Waksman R. Kirtane A.J. Torguson R. Cohen D.J. Ryan T. Raber L. Applegate R. Waxman S. Gordon P. Kaneshige K. Leon M.B. DESERT InvestigatorsCorrelates and outcomes of late and very late drug-eluting stent thrombosis: results from DESERT (International Drug-Eluting Stent Event Registry of Thrombosis).JACC Cardiovasc Interv. 2014; 7: 1093-1102Crossref PubMed Scopus (50) Google Scholar, 19Yadav M. Genereux P. Palmerini T. Caixeta A. Madhavan M.V. Xu K. Brener S.J. Mehran R. Stone G.W. SYNTAX score and the risk of stent thrombosis after percutaneous coronary intervention in patients with non-ST-segment elevation acute coronary syndromes: an ACUITY Trial Substudy.Catheter Cardiovasc Interv. 2015; 85: 1-10Crossref PubMed Scopus (25) Google Scholar, 20Palmerini T. Calabro P. Piscione F. De Servi S. Cattaneo M. Maffeo D. Toso A. Bartorelli A. Palmieri C. De Carlo M. Capodanno D. Barozzi C. Tomasi L. Della Riva D. Mariani A. Taglieri N. Reggiani L.B. Bianchi R. De Rosa R. Mariani M. Podda G. Genereux P. Stone G.W. Angiolillo D.J. Impact of gene polymorphisms, platelet reactivity, and the SYNTAX score on 1-year clinical outcomes in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention: the GEPRESS study.JACC Cardiovasc Interv. 2014; 7: 1117-1127Crossref PubMed Scopus (40) Google Scholar with stent underexpansion being the most likely causal common denominator.21Armstrong E.J. Kwa A.T. Yeo K.K. Mahmud E. Javed U. Patel M. Shunk K.A. MacGregor J.S. Low R.I. Rogers J.H. Angiographically confirmed stent thrombosis in contemporary practice: insights from intravascular ultrasound.Catheter Cardiovasc Interv. 2013; 81: 782-790Crossref PubMed Scopus (16) Google Scholar, 22Doi H. Maehara A. Mintz G.S. Yu A. Wang H. Mandinov L. Popma J.J. Ellis S.G. Grube E. Dawkins K.D. Weissman N.J. Turco M.A. Ormiston J.A. Stone G.W. Impact of post-intervention minimal stent area on 9-month follow-up patency of paclitaxel-eluting stents: an integrated intravascular ultrasound analysis from the TAXUS IV, V, and VI and TAXUS ATLAS Workhorse, Long Lesion, and Direct Stent Trials.JACC Cardiovasc Interv. 2009; 2: 1269-1275Abstract Full Text Full Text PDF PubMed Scopus (160) Google Scholar, 23Mintz G.S. Douek P. Pichard A.D. Kent K.M. Satler L.F. Popma J.J. Leon M.B. Target lesion calcification in coronary artery disease: an intravascular ultrasound study.J Am Coll Cardiol. 1992; 20: 1149-1155Abstract Full Text PDF PubMed Scopus (121) Google Scholar Although our findings are encouraging given the complexity of the lesions treated in ORBIT II, the relatively small number of patients enrolled in our study and the lack of a control arm preclude definitive conclusions regarding the utility of OAS to prevent stent thrombosis. Several reasons could underlie the favorable long-term results seen in the present study. OAS uses a principle of off-axis centrifugal force, with the orbital motion diameter being proportional to the applied speed. This orbital movement results in sanding of the entire calcified wall and might allow for greater blood flow (nonocclusive) with less heat generation and thermal injury during the procedure compared with a potentially more aggressive and occlusive atherectomy approach.24Reisman M. Shuman B.J. Harms V. Analysis of heat generation during rotational atherectomy using different operational techniques.Cathet Cardiovasc Diagn. 1998; 44: 453-455Crossref PubMed Scopus (61) Google Scholar, 25Reisman M. Shuman B.J. Dillard D. Fei R. Misser K.H. Gordon L.S. Harms V. Analysis of low-speed rotational atherectomy for the reduction of platelet aggregation.Cathet Cardiovasc Diagn. 1998; 45: 208-214Crossref PubMed Scopus (66) Google Scholar Additional imaging and mechanistic studies are required to determine the extent to which the unique mechanism of OAS contributes to the favorable outcomes observed in the present study. Approximately 12% of the ORBIT II population underwent PCI of the target lesion with BMS during the index procedure. Not surprisingly, adverse ischemic event were higher in patients with BMS compared with DES, and the use of BMS was identified as an independent predictor of MACE and TVR. Reported previously,26Zhang B.C. Wang C. Li W.H. Li D.Y. Clinical outcome of drug-eluting versus bare metal stents in patients with calcified coronary lesions: a meta-analysis.Intern Med J. 2015; 45: 203-211Crossref PubMed Scopus (8) Google Scholar this finding reiterates the dismal outcomes of BMS compared with DES when used in highly complex (i.e., heavily calcified) lesions. This finding also underlines the even more favorable results of lesion preparation using OAS, especially if only DES (specifically second generation) were used.27Onuma Y. Tanimoto S. Ruygrok P. Neuzner J. Piek J.J. Seth A. Schofer J.J. Richardt G. Wiemer M. Carrie D. Thuesen L. Dorange C. Miquel-Hebert K. Veldhof S. Serruys P.W. 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: 634-642Crossref PubMed Scopus (92) Google Scholar ORBIT II has important strengths. It is the first and largest prospective, multicenter trial including only patients with severe coronary calcification using strict angiographic enrolling criteria in the contemporary era of DES and potent antithrombotic agents. Indeed, ORBIT II enrolled patients typically excluded from standard clinical trials and still demonstrated outcomes comparable with trials excluding such patients. An independent angiographic core laboratory and independent clinical events committee reviewed and adjudicated all angiograms and adverse events. However, some limitations should be acknowledged. First, ORBIT II was a single-arm trial, with no control group. Therefore, extrapolation of the superiority of the OAS device compared with the standard strategy for treatment of severely calcified lesions could not be done. That being said, given that no device was FDA approved for treatment of calcified lesions at the time of conception of the trial, design of a head-to-head trial was deemed not necessary by the FDA. Second, adjunctive intracoronary imaging such as IVUS or optical coherence tomography was not mandated per protocol. Additional data from these imaging techniques would have been highly informative and could have provided insights on the therapeutic mechanisms and effects of OAS.28Jang J.S. Song Y.J. Kang W. Jin H.Y. Seo J.S. Yang T.H. Kim D.K. Cho K.I. Kim B.H. Park Y.H. Je H.G. Kim D.S. Intravascular ultrasound-guided implantation of drug-eluting stents to improve outcome: a meta-analysis.JACC Cardiovasc Interv. 2014; 7: 233-243Crossref PubMed Scopus (153) Google Scholar, 29Tellez A. Dattilo R. Mustapha J.A. Gongora C.A. Hyon C.M. Palmieri T. Rousselle S. Kaluza G.L. Granada J.F. Biological effect of orbital atherectomy and adjunctive paclitaxel-coated balloon therapy on vascular healing and drug retention: early experimental insights into the familial hypercholesterolaemic swine model of femoral artery stenosis.EuroIntervention. 2014; 10: 1002-1008Crossref PubMed Scopus (20) Google Scholar Third, 49 sites randomized 443 patients, with a mean of ∼8 patients enrolled per site. Because the OAS device was a novel therapeutic tool and most of the investigators had no previous experience with this device, learning curve issues must be considered, and improved outcomes may be expected with increased operator experience. The authors thank the ORBIT II investigators. The authors thank Brad J. Martinsen, PhD, and Ann Behrens, BS, of Cardiovascular Systems, Inc., and Dominic P. Francese, MPH, for their support in manuscript preparation. The ORBIT II trial was funded by Cardiovascular Systems, Inc. Dr. Généreux: Consulting fees from Cardiovascular Systems, Inc., and speaker fees from Abbott Vascular; Drs Chambers, Arthur Lee, Kim, Shlofmitz, and Lee: consulting fees from Cardiovascular Systems, Inc (ClinicalTrials.gov identifier: NCT01092416). The other authors have no relevant disclosures related to this study.