2.1

Study design and population

The ORBIT II trial ( ClinicalTrials.gov Identifier: NCT01092416 ) was a prospective, non-blinded, single-arm study conducted in 49 U.S. centers that enrolled 443 patients with severely calcified coronary lesions undergoing PCI between May 25, 2010, and November 26, 2012. The trial conformed to good clinical practice and the applicable U.S. Code of Federal Regulations. Each site received approval from its respective institutional review board and all subjects signed informed consent. The angiographic core laboratory (Cleveland Clinic Foundation, Cleveland, Ohio) performed quantitative coronary analysis and assessed for the presence of dissection or perforation.

The ORBIT II key inclusion criteria were: (1) target vessel reference diameter ≥2.5 mm and ≤4.0 mm with a stenosis ≥70% and <100% or a stenosis ≥50% and <70% with evidence of clinical ischemia via either positive stress test, fractional flow reserve value ≤0.8, or IVUS minimum lumen area ≤4.0 mm ² ; (2) target lesion length ≤40 mm; and (3) imaging evidence of severe calcium at the lesion site based on the angiographic presence of radio-opacities noted without cardiac motion prior to contrast injection, involving both sides of the arterial wall in at least one location, total length of calcium of ≥15 mm and extending partially into the target lesion; or presence of ≥270° of calcium at one cross section via IVUS. The exclusion criteria included: (1) the target vessel had a stent from a previous PCI unless the stent was on a different branch than the target lesion and was implanted more than 30 days prior with no higher than 30% in-stent restenosis; (2) recent MI, defined as creatine kinase >1 times upper limit of normal (ULN) within 30 days before the index procedure; (3) chronic renal failure unless under hemodialysis, or a serum creatinine level > 2.5 mg/dL; and (4) evidence of current left ventricular ejection fraction ≤25%.

2.2

Study device

The coronary OAS modifies calcified plaque to facilitate stent delivery and to help optimize stent expansion in severely calcified arteries. The mechanism of action is differential sanding of coronary calcification: the diamond-coated crown orbits over a specialized guidewire (ViperWire, CSI, St. Paul, Minnesota), minimizing trauma to the soft, healthy vessel wall, which flexes away from the orbiting crown. The crown expands laterally with centrifugal force, up to a maximum orbit diameter specified for low (80,000 rpm) or high (120,000 rpm) speed. The pneumatic and electric OAS configurations were used , with a crown diameter range of 1.25 mm–2.00 mm .

2.3

Study procedure

One target lesion was treated per patient. Investigators were required to implant an FDA-approved stent after performing orbital atherectomy and were not allowed to use thrombectomy, embolic protection devices, brachytherapy, or cutting balloons. Pre-dilatation after atherectomy and post-dilatation after stenting was left to the discretion of the operator. While no medications were mandated or required, dual antiplatelet therapy was recommended .

2.4

Study endpoints

The primary safety endpoint was the rate of 30-day major adverse cardiac events (MACE), defined as cardiac death, MI, and TVR. MI was defined as creatine kinase-myocardial band level >3 times ULN with or without a new pathologic Q-wave. TVR was defined as repeat revascularization of the target vessel (inclusive of the target lesion) after completion of the index procedure. Patients were followed up in clinic at 30 days, and by telephone at 1, 2, and 3 years.An independent, clinical events committee adjudicated all adverse events.

The primary efficacy endpoint was defined as procedural success: stent delivery with a residual stenosis of <50% without the occurrence of an in-hospital MACE. The secondary endpoints included angiographic success, defined as success in facilitating stent delivery with a residual stenosis <50% without severe angiographic complications during the index procedure, as well as the rate of individual severe angiographic complications during the index procedure .

2.5

Statistical analysis

Continuous variables are expressed as mean ± standard error.The Kaplan–Meier method was used to construct survival curves for the time-to-event variables. Statistical analyses were performed with either SAS Software System (SAS Institute Inc., Cary, NC, USA) or R (R Core Team2014).

2.1

Study design and population

The ORBIT II trial ( ClinicalTrials.gov Identifier: NCT01092416 ) was a prospective, non-blinded, single-arm study conducted in 49 U.S. centers that enrolled 443 patients with severely calcified coronary lesions undergoing PCI between May 25, 2010, and November 26, 2012. The trial conformed to good clinical practice and the applicable U.S. Code of Federal Regulations. Each site received approval from its respective institutional review board and all subjects signed informed consent. The angiographic core laboratory (Cleveland Clinic Foundation, Cleveland, Ohio) performed quantitative coronary analysis and assessed for the presence of dissection or perforation.

The ORBIT II key inclusion criteria were: (1) target vessel reference diameter ≥2.5 mm and ≤4.0 mm with a stenosis ≥70% and <100% or a stenosis ≥50% and <70% with evidence of clinical ischemia via either positive stress test, fractional flow reserve value ≤0.8, or IVUS minimum lumen area ≤4.0 mm ² ; (2) target lesion length ≤40 mm; and (3) imaging evidence of severe calcium at the lesion site based on the angiographic presence of radio-opacities noted without cardiac motion prior to contrast injection, involving both sides of the arterial wall in at least one location, total length of calcium of ≥15 mm and extending partially into the target lesion; or presence of ≥270° of calcium at one cross section via IVUS. The exclusion criteria included: (1) the target vessel had a stent from a previous PCI unless the stent was on a different branch than the target lesion and was implanted more than 30 days prior with no higher than 30% in-stent restenosis; (2) recent MI, defined as creatine kinase >1 times upper limit of normal (ULN) within 30 days before the index procedure; (3) chronic renal failure unless under hemodialysis, or a serum creatinine level > 2.5 mg/dL; and (4) evidence of current left ventricular ejection fraction ≤25%.

2.2

Study device

The coronary OAS modifies calcified plaque to facilitate stent delivery and to help optimize stent expansion in severely calcified arteries. The mechanism of action is differential sanding of coronary calcification: the diamond-coated crown orbits over a specialized guidewire (ViperWire, CSI, St. Paul, Minnesota), minimizing trauma to the soft, healthy vessel wall, which flexes away from the orbiting crown. The crown expands laterally with centrifugal force, up to a maximum orbit diameter specified for low (80,000 rpm) or high (120,000 rpm) speed. The pneumatic and electric OAS configurations were used , with a crown diameter range of 1.25 mm–2.00 mm .

2.3

Study procedure

One target lesion was treated per patient. Investigators were required to implant an FDA-approved stent after performing orbital atherectomy and were not allowed to use thrombectomy, embolic protection devices, brachytherapy, or cutting balloons. Pre-dilatation after atherectomy and post-dilatation after stenting was left to the discretion of the operator. While no medications were mandated or required, dual antiplatelet therapy was recommended .

2.4

Study endpoints

The primary safety endpoint was the rate of 30-day major adverse cardiac events (MACE), defined as cardiac death, MI, and TVR. MI was defined as creatine kinase-myocardial band level >3 times ULN with or without a new pathologic Q-wave. TVR was defined as repeat revascularization of the target vessel (inclusive of the target lesion) after completion of the index procedure. Patients were followed up in clinic at 30 days, and by telephone at 1, 2, and 3 years.An independent, clinical events committee adjudicated all adverse events.

The primary efficacy endpoint was defined as procedural success: stent delivery with a residual stenosis of <50% without the occurrence of an in-hospital MACE. The secondary endpoints included angiographic success, defined as success in facilitating stent delivery with a residual stenosis <50% without severe angiographic complications during the index procedure, as well as the rate of individual severe angiographic complications during the index procedure .

2.5

Statistical analysis

Continuous variables are expressed as mean ± standard error.The Kaplan–Meier method was used to construct survival curves for the time-to-event variables. Statistical analyses were performed with either SAS Software System (SAS Institute Inc., Cary, NC, USA) or R (R Core Team2014).