PERSPECTIVE CTO 1 Year Results Resolute Deck · 2019-12-11 · 2 PERSPECTIVE Study | April 2019...

DAVID E. KANDZARI, MD, FACC, FSCAI PIEDMONT HEART INSTITUTE, ATLANTA GA

PERSPECTIVE STUDY

PROCEDURAL, IN-HOSPITAL AND LONG-TERM OUTCOMES FOR CHRONIC TOTAL CORONARY OCCLUSION REVASCULARIZATION WITH THE RESOLUTE™ ZOTAROLIMUS-ELUTING STENT

PERCUTANEOUS REVASCULARIZATION AT PIEDMONT FOR CHRONIC TOTAL OCCLUSIONS SURVEY

2 PERSPECTIVE Study | April 2019

PERSPECTIVE STUDYOBJECTIVES

Evaluate procedural, early and late clinical outcomes of CTO PCI, among a consecutive, unselected CTO patient population

1. From a single-center, multiple operator CTO program with operator consensus review for appropriateness and procedural strategy

2. Examine impact of CTO PCI on:§ Self-reported health status, QoL and economic measures§ Completeness of revascularization, and its influence on health status and clinical outcome

3. Analyze CTO patients treated with Resolute Integrity™ stents (R-ZES) compared with a prespecified performance goal

©2019 Medtronic. All rights reserved. Medtronic, Medtronic logo, and Further, Together are trademarks of Medtronic. ™*Third-party brands are trademarks of their respective owners. All other brands are trademarks of a Medtronic company. For distribution in the USA only. UC201909269a EN 04/2019

3

PERSPECTIVE STUDYSTUDY BACKGROUND

§ The PERSPECTIVE Study is a single-center, investigator-initiated, observational study including a retrospective and a prospective study arm

§ The study was designed to evaluate procedural and 1-year clinical outcomes among consecutive patients undergoing attempted CTO PCI revascularization

§ The prospective arm of the PERSPECTIVE study included a pre-specified analysis of patients treated with Resolute Integrity™ ZES (R-ZES) designed to assess the safety and effectiveness of R-ZES for the treatment of CTO lesions

Study conducted at Piedmont Heart Institute (Atlanta, GA, USA), funded by Medtronic.

PERSPECTIVE Study | April 2019 ©2019 Medtronic. All rights reserved. Medtronic, Medtronic logo, and Further, Together are trademarks of Medtronic. ™*Third-party brands are trademarks of their respective owners. All other brands are trademarks of a Medtronic company. For distribution in the USA only. UC201909269a EN 04/2019

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PERSPECTIVE STUDYINVESTIGATOR-INITIATED, SINGLE CENTER, OBSERVATIONAL TRIAL PI: Dr. David Kandzari

Resolute™ ZES(N = 183)

Prospective cohort enrollment 8/2013 – 3/2016Independent QCA analysis and CEC adjudication

Angiographic Core Laboratory: PERFUSE, Boston, MA

Symptomatic ischemic heart disease due to CTO in ≥1 coronary artery lesion with TIMI 0/1 flow and estimated ≥3 mo duration

(No restrictions regarding lesion length, treatment strategy, LVEF or renal function)

Performance Goal

6mo

Clinical follow-up

SAQ and QoL

12moIn hospital

Primary Endpoints:1-year MACE (death, MI, TLR) among all subjects treated with R-ZES compared with performance goal

Key Secondary Endpoints:§ CTO procedural and technical success§ 1-year event rates of cardiac death, MI, TLR and stent thrombosis§ Change in angina frequency and QoL (Seattle Angina Questionnaire) baseline to 1 year

Clinicaltrials.gov Identifier NCT01946724Investigator-initiated study conducted at Piedmont Heart Institute (Atlanta, GA, USA) funded by Medtronic.

PERSPECTIVE Study | April 2019©2019 Medtronic. All rights reserved. Medtronic, Medtronic logo, and Further, Together are trademarks of Medtronic. ™*Third-party brands are trademarks of their respective owners. All other brands are trademarks of a Medtronic company. For distribution in the USA only. UC201909269a EN 04/2019

5

PERSPECTIVE STUDYENROLLMENT CRITERIA

Exclusion Criteria§ Any contraindication to cardiac

catheterization or any standard concomitant therapies used during/after routine cardiac catheterization and PCI

§ Hemodynamic/clinical instability

§ Estimated survival <1 year

No restrictions regarding lesion length or treatment strategy (antegrade, retrograde, hybrid; atherectomy, etc.), LVEF, recent MI or renal function

Inclusion Criteria§ Symptomatic ischemic CAD with clinical

indication for CTO revascularization

§ ≥1 de novo or previously treated native coronary artery lesion with TIMI 0/1 flow and estimated ≥3 months’ duration


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PERSPECTIVE STUDYBASELINE CLINICAL CHARACTERISTICS

N (%) or mean ± SD N = 183

Age (years) 63 ± 10

Male gender 146 (79.8)

Diabetes mellitus 65 (35.5)

Insulin requiring 23 (12.6)

Hypertension 162 (88.5)

History of smoking 105 (61.0)

Prior myocardial infarction 61 (33.3)

Angina CCSC class III/IV 112 (80.0)

LVEF ≤40% 20 (12.3)

Prior percutaneous revascularization 94 (51.4)

Prior coronary bypass surgery 48 (26.2)

Clinical indication

Stable angina 140 (80.9)

Unstable angina/myocardial infarction 7 (3.8)

Heart failure/cardiomyopathy 9 (4.9)

Abnormal noninvasive stress test 46 (25.1)


7

PERSPECTIVE STUDYBASELINE ANGIOGRAPHIC CHARACTERISTICS

N (%) or mean ± SD N = 183

Target Vessel

LAD 43 (23.5)

RCA 103 (56.3)

LCx 31 (16.9)

Left main 6 (3.3)

TIMI 0 flow 168 (93.3)

Moderate/severe calcification 99 (60.7)

Side branch involvement (≥1.5mm) 81 (42.0)

Reference vessel diameter (mm) 3.8 ± 0.7

Lesion length (mm)1 92.6 ± 36.6

Occlusion length >20 mm 129 (76.8)

Previous failure 38 (26.8)

In-stent occlusion 9 (4.9)

J-CTO score 2.4 ± 1.3

SYNTAX score 14.1 ± 6.21Stent length used as approximation for lesion length.


8

PERSPECTIVE STUDYPROCEDURAL CHARACTERISTICS AND OUTCOMES

N (%) or mean ± SD N = 183

Number of guidewires (target lesion only) 7.0 ± 4.3

Number of balloons (target lesion only) 5.0 ± 2.8

Total time elapsed at crossing (minutes) 71.8 ± 51.5

Final crossing method

Antegrade 136 (76.0)

Retrograde 37 (20.7)

Donor vessel 15 (8.4)

Failed crossing 6 (3.4)

Collaterals used n = 53

Septal 32 (60.4)

Epicardial 13 (24.5)

SVG 7 (13.2)

Epicardial and SVG 1 (1.9)

Final TIMI 3 flow 148 (91.9)

Procedural success1 169 (92.3)

Technical success2 175 (96.2)1Procedural success defined as achievement of <50% diameter stenosis and ≥ TIMI 2 antegrade flow.2Technical success defined as successful guidewire crossing with placement in the distal true lumen of CTO lesion.


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PERSPECTIVE STUDYPROCEDURAL CHARACTERISTICS AND OUTCOMES

N (%) or mean ± SD N = 183

Peri-procedural myocardial infarction

ARC definition (CK MB >3X ULN) 27 (14.8)

Protocol definition (CK MB >10X ULN) 6 (3.3)

Clinically significant perforation1 7 (3.8)

Grade III/IV perforation 6 (4.1)

Tamponade 4 (2.8)

Emergency surgery 1 (0.8)

Contrast nephropathy 1 (0.8)

Radiation dermatitis 0

Radiation (mGy) 3603 ± 2297

Contrast volume (mls) 321.1 ± 145.9

Fluoroscopy duration (minutes) 62.4 ± 44.9

Hospital stay (days) 1.2 ± 0.91Clinically significant perforation defined as any perforation resulting in hemodynamic instability and/or requiring intervention, n=145


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PERSPECTIVE STUDYCLINICAL OUTCOMES AT 1 YEAR

n (%) n = 181/183

Death 5 (2.8)

Cardiac Death 4 (2.2)

Myocardial Infarction

Protocol MI definition (CKMB >10x ULN) 6 (3.3)

ARC MI definition (CKMB >3x ULN) 29 (16.0)

Peri-procedural MI (ARC) 27 (14.9)

Spontaneous MI (ARC) 2 (1.1)

Clinically-driven TLR 2 (1.1)

Stent Thrombosis (ARC Def/Prob) 1 (0.6)

MACE

Protocol MI definition 12 (6.6)

ARC MI definition 33 (18.2)

TLF

Protocol MI definition 12 (6.6)

ARC MI definition 33 (18.2)

The protocol defined Myocardial Infarction as CKMB >10x ULN, in accordance with the SCAI definition of MI.


11

PERSPECTIVE STUDYQUALITY OF LIFE: BASELINE TO 1 YEAR

1Spertus JA, et al. Am J Cardiol. 1994; 74:1240–1244. 2Spertus JA, et al. J Am Coll Cardiol. 1995;25:333–341.

0

25

50

75

100

Physical Limitation Angina Frequency Quality of Life Summary Score

Pati

ent R

epo

rted

Mea

n S

core

s o

n S

eatt

le A

ngin

a Q

uest

ionn

aire

1,2

(%)

Baseline (n = 176)

1 Year (n = 164)

P < 0.001 P < 0.001 P < 0.001 P < 0.001

Hig

her i

s be

tter


12

PERSPECTIVE STUDYANGINA FREQUENCY: BASELINE TO 1 YEAR

34

8426

13

40

2

0%

25%

50%

75%

100%

Baseline (n = 176) 1 Year (n = 164)

Daily/WeeklyMonthlyNone

Pati

ent R

epo

rted

Ang

ina

Freq

uenc

y o

n S

eatt

le A

ngin

a Q

uest

ionn

aire

1,2

1Spertus JA, et al. Am J Cardiol. 1994; 74:1240–1244. 2Spertus JA, et al. J Am Coll Cardiol. 1995;25:333–341.

P < 0.0001


13

PERSPECTIVE STUDYCONCLUSIONS

§ In the PERSPECTIVE Study representing contemporary technique with R-ZES implantation, we observed favorable procedural success, health status improvement and 1-yr clinical outcomes in a clinically indicated, high lesion complexity patient population

§ Despite high lesion complexity and extensive stent length, treatment in CTO lesions with Resolute™ ZES was associated with:§ Low rates of repeat revascularization (1.1% TLR), cardiac death (2.2%) and definite ST (0.6%) at 1 year

§ Consistent with outcomes observed in less complex disease

§ A significant improvement in both observer- and patient-reported health status

Study was not powered for individual clinical event rates, only for the MACE composite.


14

RESOLUTE ONYX™INDICATIONS, SAFETY, AND WARNINGS

IndicationsThe Resolute Onyx™ Zotarolimus-Eluting Coronary Stent System is indicated for improving coronary luminal diameters in patients, including those with diabetes mellitus, with symptomatic ischemic heart disease due to de novo lesions of length ≤ 35 mm in native coronary arteries with reference vessel diameters of 2.0 mm to 5.0 mm. In addition, the Resolute Onyx™ Zotarolimus-Eluting Coronary Stent System is indicated for treating de novo chronic total occlusions.

ContraindicationsThe Resolute Onyx™ Zotarolimus-Eluting Coronary Stent System is contraindicated for use in: § Patients with a known hypersensitivity or allergies to aspirin, heparin, bivalirudin, clopidogrel, prasugrel, ticagrelor, ticlopidine, drugs such as zotarolimus, tacrolimus, sirolimus, everolimus, or similar drugs or any other analogue or derivative § Patients with a known hypersensitivity to the cobalt-based alloy (cobalt, nickel, chromium, and molybdenum) or platinum-iridium alloy § Patients with a known hypersensitivity to the BioLinx™ polymer or its individual components. Coronary artery stenting is contraindicated for use in: § Patients in whom antiplatelet and/or anticoagulation therapy is contraindicated § Patients who are judged to have a lesion that prevents complete inflation of an angioplasty balloon or proper placement of the stent or stent delivery system

WarningsPlease ensure that the inner package has not been opened or damaged as this would indicate the sterile barrier has been breached. § The use of this product carries the same risks associated with coronary artery stent implantation procedures, which include subacute and late vessel thrombosis, vascular complications, and/or bleeding events. § This product should not be used in patients who are not likely to comply with the recommended antiplatelet therapy.

Precautions§ Only physicians who have received adequate training should perform implantation of the stent. § Subsequent stent restenosis or occlusion may require repeat catheter based treatments (including balloon dilatation) of the arterial segment containing the stent. The long-term outcome following repeat catheter-based treatments of previously implanted stents is not well characterized. § The risks and benefits of the stent implantation should be assessed for patients with a history of severe reaction to contrast agents. § Do not expose or wipe the product with organic solvents such as alcohol. § The use of a drug-eluting stent (DES) outside of the labeled indications, including use in patients with more tortuous anatomy, may have an increased risk of adverse events, including stentthrombosis, stent embolization, MI, or death. § Care should be taken to control the position of the guide catheter tip during stent delivery, stent deployment, and balloon withdrawal. Before withdrawing the stent delivery system, confirm complete balloon deflation using fluoroscopy to avoid arterial damage caused by guiding catheter movement into the vessel. § Stent thrombosis is a low-frequency event that is frequently associated with myocardial infarction (MI) or death. Data from the RESOLUTE clinical trials have been prospectively evaluated and adjudicated using the definition developed by the Academic Research Consortium (ARC). The safety andeffectiveness of the Resolute Onyx™ stent have not yet been established in the following patient populations: § Patients with target lesions that were treated with prior brachytherapy or the use of brachytherapy to treat n-stent restenosis of a Resolute Onyx™ stent§ Women who are pregnant or lactating § Men intending to father children § Pediatric patients § Patients with coronary artery reference vessel diameters of < 2.0 mm or > 5.0 mm § Patients with evidence of an acute ST-elevation MI within 72 hours of intended stent implantation § Patients with vessel thrombus at the lesion site § Patients with lesions located in a saphenous vein graft, in the left main coronary artery, ostial lesions, or bifurcation lesions § Patients with diffuse disease or poor flow distal to identified lesions § Patients with three-vessel disease. The safety and effectiveness of the Resolute Onyx™ stent have not been established in the cerebral, carotid, or peripheral vasculature.

Potential Adverse EventsOther risks associated with using this device are those associated with percutaneous coronary diagnostic (including angiography and IVUS) and treatment procedures. These risks (in alphabetical order) may include but are not limited to: § Abrupt vessel closure § Access site pain, hematoma, or hemorrhage § Allergic reaction (to contrast, antiplatelet therapy, stent material, or drug and polymer coating) § Aneurysm, pseudoaneurysm, or arteriovenous fistula (AVF) § Arrhythmias, including ventricular fibrillation § Balloon rupture § Bleeding § Cardiac tamponade § Coronary artery occlusion, perforation, rupture, or dissection § Coronary artery spasm § Death § Embolism (air, tissue, device, or thrombus) § Emergency surgery: peripheral vascular or coronary bypass § Failure to deliver the stent § Hemorrhage requiring transfusion § Hypotension/hypertension § Incomplete stent apposition § Infection or fever § MI § Pericarditis § Peripheral ischemia/peripheral nerve injury § Renal failure § Restenosis of the stented artery § Shock/pulmonary edema § Stable or unstable angina § Stent deformation, collapse, or fracture § Stent migration or embolization § Stent misplacement § Stroke/transient ischemic attack § Thrombosis (acute,subacute, or late)

Adverse Events Related to ZotarolimusPatients’ exposure to zotarolimus is directly related to the total amount of stent length implanted. The actual side effects/complications that may be associated with the use of zotarolimus are not fully known. The adverse events that have been associated with the intravenous injection of zotarolimus in humans include but are not limited to: § Anemia § Diarrhea § Dry skin § Headache § Hematuria § Infection § Injection site reaction § Pain (abdominal, arthralgia, injection site) § Rash

Please reference appropriate product Instructions for Use for more information regarding indications, warnings, precautions, andpotential adverse events.

CAUTION: Federal (USA) law restricts this device to sale by or on the order of a physician.


15

RESOLUTE INTEGRITY™

INDICATIONS, SAFETY, AND WARNINGS

IndicationsThe Resolute Integrity Zotarolimus-Eluting Coronary Stent System is indicated for improving coronary luminal diameters in patients, including those with diabetes mellitus, with symptomatic ischemic heart disease due to de novo lesions of length ≤35 mm in native coronary arteries with reference vessel diameters of 2.25 mm to 4.20 mm. In addition, the Resolute Integrity Zotarolimus-Eluting Coronary Stent System is indicated for treatment of de novo chronic total occlusions.

ContraindicationsThe Resolute Integrity Zotarolimus-Eluting Coronary Stent System is contraindicated for use in: § Patients with a known hypersensitivity or allergies to aspirin, heparin, bivalirudin, clopidogrel, prasugrel, ticagrelor, ticlopidine, drugs such as zotarolimus, tacrolimus, sirolimus, everolimus or similar drugs or any other analogue or derivative § Patients with a known hypersensitivity to the cobalt-based alloy (cobalt, nickel, chromium and molybdenum) § Patients with a known hypersensitivity to the BioLinx™ polymer or its individual components

Coronary artery stenting is contraindicated for use in: § Patients in whom antiplatelet and/or anticoagulation therapy is contraindicated § Patients who are judged to have a lesion that prevents complete inflation of an angioplasty balloon or proper placement of the stent or stent delivery system

Warnings§ Please ensure that the inner package has not been opened or damaged as this would indicate the sterile barrier has been breached. § The use of this product carries the same risks associated with coronary artery stent implantation procedures, which include subacute and late vessel thrombosis, vascular complications and/or bleeding events. § This product should not be used in patients who are not likely to comply with the recommended antiplatelet therapy.

Precautions§ Only physicians who have received adequate training should perform implantation of the stent. § Stent placement should only be performed at hospitals where emergency coronary artery bypass graft surgery can be readily performed. § Subsequent stent restenosis or occlusion may require repeat catheter-based treatments (including balloon dilatation) of the arterial segment containing the stent. The long-term outcome following repeat catheter-based treatments of previously implanted stents is not well characterized. § The risks and benefits of the stent implantation should be assessed for patients with a history of severe reaction to contrast agents. § Do not expose or wipe the product with organic solvents such as alcohol. § When drug-eluting stents (DES) are used outside the specified Indications for Use, patient outcomes may differ from the results observed in the RESOLUTE pivotal clinical trials. § Compared to use within the specified Indications for Use, the use of DES in patients and lesions outside of the labeled indications, including more tortuous anatomy, may have an increased risk of adverse events, including stent thrombosis, stent embolization, myocardial infarction (MI) or death. § Care should be taken to control the position of the guide catheter tip during stent delivery, deployment and balloon withdrawal. Before withdrawing the stent delivery system, visually confirm complete balloon deflation by fluoroscopy to avoid guiding catheter movement into the vessel and subsequent arterial damage. § Stent thrombosis is a low-frequency event that is frequently associated with MI or death. Data from the RESOLUTE clinical trials have been prospectively evaluated and adjudicated using the definitiondeveloped by the Academic Research Consortium (ARC).

The safety and effectiveness of the Resolute Integrity stent have not yet been established in the following patient populations:§ Patients with target lesions which were treated with prior brachytherapy or the use of brachytherapy to treat in-stent restenosis of a Resolute Integrity stent § Women who are pregnant or lactating § Men intending to father children § Pediatric patients § Patients with coronary artery reference vessel diameters of < 2.25 mm or > 4.20 mm § Patients with coronary artery lesions longer than 35 mm or requiring more than one Resolute Integrity stent § Patients with evidence of an acute MI within 72 hours of intended stent implantation § Patients with vessel thrombus at the lesion site § Patients with lesions located in a saphenous vein graft, in the left main coronary artery, ostial lesions or bifurcation lesions § Patients with diffuse disease or poor flow distal to identified lesions § Patients with tortuous vessels in the region of the target vessel or proximal to the lesion § Patients with in-stent restenosis § Patients with moderate or severe lesion calcification at the target lesion § Patients with three-vessel disease § Patients with a left ventricular ejection fraction of < 30% § Patients with a serum creatinine of > 2.5 mg/dl § Patients with longer than 24 months of follow-up

The safety and effectiveness of the Resolute Integrity stent have not been established in the cerebral, carotid or peripheral vasculature.

Potential Adverse EventsOther risks associated with using this device are those associated with percutaneous coronary diagnostic (including angiography and IVUS) and treatment procedures. These risks (in alphabetical order) may include but are not limited to: § Abrupt vessel closure § Access site pain, hematoma or hemorrhage § Allergic reaction (to contrast, antiplatelet therapy, stent material, or drug and polymer coating) § Aneurysm, pseudoaneurysm or arteriovenous fistula (AVF) § Arrhythmias, including ventricular fibrillation § Balloon rupture § Bleeding § Cardiac tamponade § Coronary artery occlusion, perforation, rupture or dissection § Coronary artery spasm § Death § Embolism (air, tissue, device or thrombus) § Emergency surgery: peripheral vascular or coronary bypass § Failure to deliver the stent § Hemorrhage requiring transfusion § Hypotension/hypertension § Incomplete stent apposition § Infection or fever § MI § Pericarditis § Peripheral ischemia/peripheral nerve injury § Renal failure § Restenosis of the stented artery § Shock/pulmonary edema § Stable or unstable angina § Stent deformation, collapse or fracture § Stent migration (or embolization) § Stent misplacement § Stroke/transient ischemic attack § Thrombosis (acute, subacute or late)

Adverse Events Related to ZotarolimusPatients’ exposure to zotarolimus is directly related to the total amount of stent length implanted. The actual side effects/complications that may be associated with the use of zotarolimus are not fully known. The adverse events that have been associated with the intravenous injection of zotarolimus in humans include but are not limited to: § Anemia § Diarrhea § Dry skin § Headache § Hematuria § Infection § Injection site reaction § Pain (abdominal, arthralgia, injection site) § Rash

Please reference appropriate product Instructions for Use for more information regarding indications, warnings, precautions and potential adverse events.

CAUTION: Federal (USA) law restricts this device to sale by or on the order of a physician.


16 PERSPECTIVE Study | April 2019©2019 Medtronic. All rights reserved. Medtronic, Medtronic logo, and Further, Together are trademarks of Medtronic. ™*Third-party brands are trademarks of their respective owners. All other brands are trademarks of a Medtronic company. For distribution in the USA only. UC201909269a EN 04/2019

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