FIVE-YEAR CLINICAL OUTCOMES FOR RESOLUTE ZOTAROLIMUS ... · ROBERT YEH,1HENNING...

ROBERT YEH,1 HENNING KELBÆK,2 FRANZ-JOSEF NEUMANN,3

PATRICK SERRUYS,4 STEPHAN WINDECKER,5 JORGE BELARDI,6

BO XU,7 SHUBIN QIAO,7 MINGLEI LIU8 AND SIGMUND SILBER9

FIVE-YEAR CLINICAL OUTCOMES FOR RESOLUTE ZOTAROLIMUS-ELUTING STENTS IN TOTAL OCCLUSIONS

1 Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; 2 Cardiac Catheterisation Laboratory, Zealand University Hospital, Roskilde, Denmark; 3 Heart Center Bad Krozingen, Bad Krozingen, Germany; 4

Erasmus Medical Center, Rotterdam, The Netherlands; 5 Department of Interventional Cardiology, Bern University Hospital, Bern, Switzerland; 6 Instituto Cardiovascular de Buenos Aires, Buenos Aires, Argentina; 7 Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Beijing, China; 8 Medtronic PLC, Santa Rosa, CA, USA; 9 Heart Center at the Isar, Munich, Germany

2 Five-Year Clinical Outcomes | April 2019

RESOLUTE POOLED – TOTAL OCCLUSIONS SUBGROUPBACKGROUND

§ Long-term outcomes of patients with drug-eluting stents (DES) in total occlusions (TO) are not well known.

§ The current analysis compares 5-year clinical outcomes for patients implanted with Resolute DES in chronic or non-chronic TO lesions versus those who were treated for lesions without a total occlusion.

©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. UC201909272a EN 04/2019

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RESOLUTE POOLED – TOTAL OCCLUSIONS SUBGROUPMETHODS

§ Data for this post-hoc analysis was pooled from § Resolute All-Comers1,2

§ Resolute International3,4

§ Resolute China RCT5

§ Resolute China Registry6

§ Three groups of patients7 were compared in Kaplan-Meier cumulative curves to 5 years: 1. CTO: chronic TO patients (N = 436)2. Non-chronic TO patients (N = 467)3. Patients without TO (N = 4584)

1Serruys PW, et al. N Engl J Med. 2010;363:136-46 4Belardi JA, et al. J Interv Cardiol. 2013;26(5):515-232Iqbal J, et al. Circ Cardiovasc Interv. 2015;8:e002230 5Xu B, et al. JACC Cardiovasc Interv. 2013;6(7):664-703Neumann FJ, et al. EuroIntervention. 2012;7(10):1181-8 6Qiao S, et al. Am J Cardiol. 2014;113(4):613-20

7Note: Because R-AC study did not differentiate between CTO and TO, the following definitions were used to assign to groups: CTO group: all CTO patients from R-INT, R-China RCT and R-China Reg (investigator reported by history) plus total occlusion (TIMI 0) patients from R-AC excluding those with AMI.TO group: all remaining TO patients from R-INT, R-China RCT and R-China Reg.No occlusion: consists of the remaining patients without a TO or CTO

RCT 1:1 vs. Xience V™* EES (R=1140; X=1152)

Non-RCT Observational (R=2349)

RCT 1:1 vs. Taxus™* PES (R=198; T=202)

Non-RCT Observational (R=1800)

5 yr

3 yr

5 yr

5 yr

Five-Year Clinical Outcomes | 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. UC201909272a EN 04/2019

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RESOLUTE POOLED – TOTAL OCCLUSIONS SUBGROUPBASELINE CHARACTERISTICS

(% or mean±SD)CTO group

(N = 436)TO group (N = 467)

No Occlusion (N = 4584)

P (CTO vs NO)

P (TO vs NO)

Age (years) 60.8 ± 11.2 60.0 ± 11.6 63.3 ± 10.9 <0.001 <0.001

Female gender 17.2 24.6 23.6 0.002 0.61

Diabetes mellitus 26.1 26.6 28.9 0.22 0.28

Insulin dependent 4.6 4.9 6.2 0.19 0.29

Hypertension 64.7 57.6 68.5 0.10 <0.001

Hyperlipidemia 52.1 48.6 56.5 0.08 0.001

Current smoker 30.3 45.8 27.2 0.16 <0.001

Prior MI 37.7 33.5 29.4 <0.001 0.06

Prior PCI 20.9 10.3 25.7 0.03 <0.001

ACS 47.0 78.4 53.3 0.01 <0.001

Acute MI (within 72 hrs) 16.1 70.4 13.2 0.09 <0.001


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RESOLUTE POOLED – TOTAL OCCLUSIONS SUBGROUPANGIOGRAPHIC CHARACTERISTICS

(% or mean±SD)CTO group

(N = 436)TO group (N = 467)

No Occlusion (N = 4584)

P (CTO vs NO)

P (TO vs NO)

Vessel location (pt level)

LAD 51.6 48.2 56.2 0.06 <0.001

LCX 27.1 26.6 27.5 0.86 0.67

RCA 50.7 45.0 30.8 <0.001 <0.001

Left main 0.9 1.5 2.6 0.03 0.15

RVD (mm) 2.9 ± 0.5 2.9 ± 0.5 2.9 ± 0.5 0.19 0.15

Number of lesions treated/pt 1.6 ± 0.8 1.5 ± 0.8 1.4 ± 0.7 <0.001 0.01

Total stent length/pt 53.9 ± 35.9 41.3 ± 28.2 33.4 ± 22.1 <0.001 <0.001


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RESOLUTE POOLED – TOTAL OCCLUSIONS SUBGROUPCLINICAL OUTCOMES TO 5 YEARS

13.24

5.33

4.19

5.79

6.97

1.18

12.46

5.09

3.2

6.88

9.07

2.55

13.28

4.794.31

6.46

8.84

1.33

0

5

10

15

TLF Cardiac Death TV-MI TLR TVR ST (def/prob)

CTO (N = 436)

Non-chronic TO (N = 467)

No TO (N=4584)

P=0.96

P=0.64

P=0.54

P=0.70

P=0.52

P=0.11

Cum

ulat

ive

Inci

denc

e (%

)


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RESOLUTE POOLED – TOTAL OCCLUSIONS SUBGROUPTARGET LESION FAILURE TO 5 YEARS

Number at riskCTO 436 433 403 384 351 207

Non-Chronic TO

467 464 434 410 355 240

Non-TO 4584 4537 4213 4040 3612 2180

13.2%12.5%

13.3%

0 12 24 36 48 60

0%

5%

10%

15%

20%

Time After Initial Procedure (months)

Cum

ulat

ive

Inci

denc

e of

TLF

Log-Rank P=0.96CTO

Non-TO

Non-Chronic TO

Number at risk

CTO 436 433 403 384 351 207

Non-Chronic TO 467 464 434 410 355 240

Non-TO 4584 4537 4213 4040 3612 2180


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RESOLUTE POOLED – TOTAL OCCLUSIONS SUBGROUPCARDIAC DEATH OR MI TO 5 YEARS

8.5%

7.1%

8.6%

0 12 24 36 48 60

0%

5%

10%

15%

20%


Cum

ulat

ive

Inci

denc

e of

Card

iac

Deat

h or

TVM

ILog-Rank P=0.64CTO

Non-TO

Non-Chronic TO

Number at risk

CTO 436 433 411 397 363 215

Non-Chronic TO 467 465 445 430 373 254

Non-TO 4584 4540 4315 4188 3749 2263

Five-Year Clinical Outcomes | 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. UC201909272a EN 04/2019

9

RESOLUTE POOLED – TOTAL OCCLUSIONS SUBGROUPTARGET VESSEL REVASCULARIZATION TO 5 YEARS

9.1%

8.8%

0 12 24 36 48 60

0%

5%

10%

15%

20%


Cum

ulat

ive

Inci

denc

e of

TVR

Log-Rank P=0.52CTO

Non-TO

Non-Chronic TO

7.0%

Number at riskCTO 436 436 410 390 354 211

Non-Chronic TO 467 466 440 416 360 237

Non-TO 4584 4577 4286 4094 3655 2202


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RESOLUTE POOLED – TOTAL OCCLUSIONS SUBGROUPSTENT THROMBOSIS TO 5 YEARS

Log-Rank P=0.11

0 12 24 36 48 60

0%

4%

6%

8%

10%


Cum

ulat

ive

Inci

denc

e of

Def

or P

rob

ST

2%

1.2%

2.6%

1.3%

CTO

Non-TO

Non-Chronic TO

Number at risk

CTO 436 436 421 407 371 220

Non-Chronic TO 467 466 452 437 379 256

Non-TO 4584 4577 4422 4302 3855 2322


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RESOLUTE POOLED – TOTAL OCCLUSIONS SUBGROUPLIMITATIONS

§ Despite differences in demographic data, which represent differences in their clinical status, patients with CTO, TO and non-occluded lesions had similar outcomes.

§ The (C)TO lesions included in this post-hoc analysis seemed to be relatively short and simple, so that outcomes in more complex CTO lesions may be different.


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RESOLUTE POOLED – TOTAL OCCLUSIONS SUBGROUPCONCLUSIONS

§ The current analysis of 903 patients with totally occluded lesions treated in Europe and China within the RESOLUTE Global Clinical Program supports the safety and efficacy of Resolute DES in this complex lesion subgroup.

§ These data suggest that patients treated with Resolute DES after recanalization of totally occluded coronary lesions have long term results that are comparable to those with non-occlusive disease.


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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.


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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 > 2.5mg/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.


15

©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. UC201909272a EN 04/2019


FIVE-YEAR CLINICAL OUTCOMES FOR RESOLUTE ZOTAROLIMUS ... · ROBERT YEH,1HENNING...

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Transcript of FIVE-YEAR CLINICAL OUTCOMES FOR RESOLUTE ZOTAROLIMUS ... · ROBERT YEH,1HENNING...