2.1

Trial patients

Patients greater than 18 years of age meeting the following criteria were enrolled in the study: 1) target lesion was a de novo coronary lesion classified as mild to severely calcified; the target lesion had a calcified lesion arc in at least 1 quadrant as visualized by IVUS; 2) native coronary artery with a stenosis of ≥ 50% and < 100% crossable with the atherectomy guide wire; 3) target vessel reference diameter ≥ 2.5 mm and ≤ 4.0 mm by angiogram; 4) main target vessel classified as Thrombolysis and Myocardial Infarction (TIMI) grade 3 flow and 5) lesion length ≤ 25 mm.

Patients were excluded if there was evidence of an acute myocardial infarction (MI) within 72 hours prior to the intended treatment or previous percutaneous coronary intervention (PCI) or surgery on any vessel within 30 days prior to the intended intervention. Additionally, only one lesion could be treated during the index procedure. If the patient had two lesions, the patient was staged and the non-target lesion was treated first. Per study protocol, the creatine kinase-myocardial band (CK-MB) levels were required to be within laboratory normal ranges at least 12 hours after non-target lesion treatment and within 8 hours prior to treating the target lesion.

2.2

Device description

The Diamondback 360º® Coronary Orbital Atherectomy System (Cardiovascular Systems, Inc., St. Paul, MN) has been successfully used to treat calcified peripheral vascular stenosis since 2007. The system has been adapted for use in coronary arteries. The OAS is a percutaneous, endovascular system that incorporates the use of centrifugal force and differential sanding to modify calcified lesions. The OAS utilizes an eccentrically mounted, diamond-coated crown ( Fig. 1 ) that orbits over an atherectomy guide wire at high speeds. Position of the crown within the vessel is controlled via a control handle ( Fig. 2 ). As treatment proceeds, a thin layer of plaque is removed with each pass of the crown. This allows the crown to “sand” away the calcified lesion while the more elastic tissue flexes away from the crown to increase lumen size and modify plaque compliance, depending on the rotational speed chosen. The crown’s orbital diameter expands radially via centrifugal force. The orbital atherectomy procedure removes the calcified stenotic lesion material to increase vessel compliance prior to balloon angioplasty and stent placement, which may lead to reduced acute vascular injury.

An eccentrically mounted, diamond-coated crown orbits over an atherectomy guide wire and removes a thin a layer of plaque with each pass of the crown.

The control knob on the control handle allows for positioning the crown within the vessel.

2.3

Methods

Overall, 50 patients were enrolled in the ORBIT I multi-center study. One of the participating centers (Care Institute of Medical Sciences (CIMS), Ahmedabad, India) enrolled and followed 33 of these 50 ORBIT I patients were followed up at Care Institute of Medical Sciences (CIMS), Ahmedabad, India. Ethics committee approval was received and Good Clinical Practice (GCP) guidelines were followed for the conduct of the study. Patients who met the inclusion/exclusion criteria and gave written informed consent were enrolled.

All procedures were performed electively. Patients underwent percutaneous coronary treatment in the standard fashion. Choice of anticoagulation was at the operators’ discretion but activated clotting time (ACT) was measured to assure appropriate level of anticoagulation. Heparin or bivalirudin was given to maintain an ACT > 250 seconds or an ACT of > 200 seconds with concomitant use of glycoprotein IIb/IIIa (GpIIb/IIIa) as per protocol.

The OAS procedure was initiated by crossing the coronary lesion with the ViperWire Advance® coronary guide wire (Cardiovascular Systems, Inc., St. Paul, MN). Predilation with balloon angioplasty could be performed at the investigators’ discretion to allow introduction of the IVUS imaging catheter for pre-procedural scan completion. The OAS procedure was initiated with the smallest crown size (choice of 1.25, 1.5, 1.75 or 2.0 mm) that was necessary to modify the calcified plaque and facilitate the delivery of the stent. OAS rotational crown speed ranged from 80,000 to 120,000 rotations per minute (rpm). After OAS treatment, dilatation with balloon angioplasty before and after stenting was allowed. Post-procedure residual stenosis was reported as a percentage of the vessel diameter, which was measured angiographically and evaluated by the treating physician. Device success was defined as a final achievement of ≤ 50% residual stenosis of the target lesion after OAS use only (before stent placement or any other adjunctive treatment), without a device malfunction. Procedural success was defined as ≤ 20% residual stenosis after stent placement. Debulking was based on pre- and post-diameter stenosis of lesions treated with OAS.

Post-stent placement, antiplatelet therapy was given at the discretion of the investigator and consisted of ≥ 75 mg of aspirin given indefinitely and clopidogrel 75 mg daily given according to the stent manufacturer’s recommendation (typically, for 1 year if a DES stent was implanted). Patients were followed at 30 days, 3 months, 6 months, 2 years and 3 years post-index treatment. The safety of the OAS was evaluated by procedural success, device success, TLR and overall major adverse cardiovascular events (MACE) rates at 6 months, 2 years and 3 years. The MACE rate was defined as a composite endpoint of cardiac death, MI and need for TLR. Per the study protocol, a Q-wave MI was defined as the development of a new pathological Q-wave greater than 1 mV in two or more contiguous leads while a non-Q-wave MI was defined as post-procedure elevation of CK to 3 times the upper lab normal value with elevated CK-MB and without pathological Q-waves present on the electrocardiogram. TLR was defined as any repeat revascularization of the target lesion. Reporting of angiographic complications consisted of no flow or slow flow due to distal embolization, abrupt or threatened closure of the treated vessel, spasm requiring any surgical intervention (which could not be resolved via medications), dissection, perforation and other events seen angiographically.

Since the study was not designed with a control or powered for statistical significance, the treatment group for analysis was based on all subjects that consented, met the selection criteria and intended to be treated with the OAS (intent to treat). All endpoints and data were reported using descriptive analysis. Where the item was compared to the baseline, a p -value was calculated.

2.1

Trial patients

Patients greater than 18 years of age meeting the following criteria were enrolled in the study: 1) target lesion was a de novo coronary lesion classified as mild to severely calcified; the target lesion had a calcified lesion arc in at least 1 quadrant as visualized by IVUS; 2) native coronary artery with a stenosis of ≥ 50% and < 100% crossable with the atherectomy guide wire; 3) target vessel reference diameter ≥ 2.5 mm and ≤ 4.0 mm by angiogram; 4) main target vessel classified as Thrombolysis and Myocardial Infarction (TIMI) grade 3 flow and 5) lesion length ≤ 25 mm.

Patients were excluded if there was evidence of an acute myocardial infarction (MI) within 72 hours prior to the intended treatment or previous percutaneous coronary intervention (PCI) or surgery on any vessel within 30 days prior to the intended intervention. Additionally, only one lesion could be treated during the index procedure. If the patient had two lesions, the patient was staged and the non-target lesion was treated first. Per study protocol, the creatine kinase-myocardial band (CK-MB) levels were required to be within laboratory normal ranges at least 12 hours after non-target lesion treatment and within 8 hours prior to treating the target lesion.

2.2

Device description

The Diamondback 360º® Coronary Orbital Atherectomy System (Cardiovascular Systems, Inc., St. Paul, MN) has been successfully used to treat calcified peripheral vascular stenosis since 2007. The system has been adapted for use in coronary arteries. The OAS is a percutaneous, endovascular system that incorporates the use of centrifugal force and differential sanding to modify calcified lesions. The OAS utilizes an eccentrically mounted, diamond-coated crown ( Fig. 1 ) that orbits over an atherectomy guide wire at high speeds. Position of the crown within the vessel is controlled via a control handle ( Fig. 2 ). As treatment proceeds, a thin layer of plaque is removed with each pass of the crown. This allows the crown to “sand” away the calcified lesion while the more elastic tissue flexes away from the crown to increase lumen size and modify plaque compliance, depending on the rotational speed chosen. The crown’s orbital diameter expands radially via centrifugal force. The orbital atherectomy procedure removes the calcified stenotic lesion material to increase vessel compliance prior to balloon angioplasty and stent placement, which may lead to reduced acute vascular injury.

An eccentrically mounted, diamond-coated crown orbits over an atherectomy guide wire and removes a thin a layer of plaque with each pass of the crown.

The control knob on the control handle allows for positioning the crown within the vessel.

2.3

Methods

Overall, 50 patients were enrolled in the ORBIT I multi-center study. One of the participating centers (Care Institute of Medical Sciences (CIMS), Ahmedabad, India) enrolled and followed 33 of these 50 ORBIT I patients were followed up at Care Institute of Medical Sciences (CIMS), Ahmedabad, India. Ethics committee approval was received and Good Clinical Practice (GCP) guidelines were followed for the conduct of the study. Patients who met the inclusion/exclusion criteria and gave written informed consent were enrolled.

All procedures were performed electively. Patients underwent percutaneous coronary treatment in the standard fashion. Choice of anticoagulation was at the operators’ discretion but activated clotting time (ACT) was measured to assure appropriate level of anticoagulation. Heparin or bivalirudin was given to maintain an ACT > 250 seconds or an ACT of > 200 seconds with concomitant use of glycoprotein IIb/IIIa (GpIIb/IIIa) as per protocol.

The OAS procedure was initiated by crossing the coronary lesion with the ViperWire Advance® coronary guide wire (Cardiovascular Systems, Inc., St. Paul, MN). Predilation with balloon angioplasty could be performed at the investigators’ discretion to allow introduction of the IVUS imaging catheter for pre-procedural scan completion. The OAS procedure was initiated with the smallest crown size (choice of 1.25, 1.5, 1.75 or 2.0 mm) that was necessary to modify the calcified plaque and facilitate the delivery of the stent. OAS rotational crown speed ranged from 80,000 to 120,000 rotations per minute (rpm). After OAS treatment, dilatation with balloon angioplasty before and after stenting was allowed. Post-procedure residual stenosis was reported as a percentage of the vessel diameter, which was measured angiographically and evaluated by the treating physician. Device success was defined as a final achievement of ≤ 50% residual stenosis of the target lesion after OAS use only (before stent placement or any other adjunctive treatment), without a device malfunction. Procedural success was defined as ≤ 20% residual stenosis after stent placement. Debulking was based on pre- and post-diameter stenosis of lesions treated with OAS.

Post-stent placement, antiplatelet therapy was given at the discretion of the investigator and consisted of ≥ 75 mg of aspirin given indefinitely and clopidogrel 75 mg daily given according to the stent manufacturer’s recommendation (typically, for 1 year if a DES stent was implanted). Patients were followed at 30 days, 3 months, 6 months, 2 years and 3 years post-index treatment. The safety of the OAS was evaluated by procedural success, device success, TLR and overall major adverse cardiovascular events (MACE) rates at 6 months, 2 years and 3 years. The MACE rate was defined as a composite endpoint of cardiac death, MI and need for TLR. Per the study protocol, a Q-wave MI was defined as the development of a new pathological Q-wave greater than 1 mV in two or more contiguous leads while a non-Q-wave MI was defined as post-procedure elevation of CK to 3 times the upper lab normal value with elevated CK-MB and without pathological Q-waves present on the electrocardiogram. TLR was defined as any repeat revascularization of the target lesion. Reporting of angiographic complications consisted of no flow or slow flow due to distal embolization, abrupt or threatened closure of the treated vessel, spasm requiring any surgical intervention (which could not be resolved via medications), dissection, perforation and other events seen angiographically.

Since the study was not designed with a control or powered for statistical significance, the treatment group for analysis was based on all subjects that consented, met the selection criteria and intended to be treated with the OAS (intent to treat). All endpoints and data were reported using descriptive analysis. Where the item was compared to the baseline, a p -value was calculated.