throbber
J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S
`
`© 2 0 1 1 B Y T H E A M E R I C A N C O L L E G E O F C A R D I O L O G Y F O U N D A T I O N
`
`P U B L I S H E D B Y E L S E V I E R I N C .
`
`V O L . 4 , N O . 8 , 2 0 1 1
`
`I S S N 1 9 3 6 - 8 7 9 8 / $ 3 6 . 0 0
`
`D O I : 1 0 . 1 0 1 6 / j . j c i n . 2 0 1 1 . 0 5 . 0 1 4
`
`STATE-OF-THE-ART PAPER
`
`Saphenous Vein Graft Intervention
`
`Michael S. Lee, MD,* Seung-Jung Park, MD,‡ David E. Kandzari, MD,§
`Ajay J. Kirtane, MD, SM,储 William F. Fearon, MD,† Emmanouil S. Brilakis, MD, PHD,¶
`Paul Vermeersch, MD,# Young-Hak Kim, MD,‡ Ron Waksman, MD,**
`Julinda Mehilli, MD,†† Laura Mauri, MD,‡‡ Gregg W. Stone, MD储
`Los Angeles and Palo Alto, California; Seoul, South Korea; Atlanta, Georgia; New York, New York;
`Dallas, Texas; Antwerp, Belgium; Washington, DC; Munich, Germany; and Boston, Massachusetts
`
`Saphenous vein grafts are commonly used conduits for surgical revascularization of coronary arteries but
`are associated with poor long-term patency rates. Percutaneous revascularization of saphenous vein grafts
`is associated with worse clinical outcomes including higher rates of in-stent restenosis, target vessel revas-
`cularization, myocardial infarction, and death compared with percutaneous coronary intervention of native
`coronary arteries. Use of embolic protection devices is a Class I indication according to the American College of
`Cardiology/American Heart Association guidelines to decrease the risk of distal embolization, no-reflow, and
`periprocedural myocardial infarction. Nonetheless, these devices are underused in clinical practice. Various phar-
`macological agents are available that may also reduce the risk of or mitigate the consequences of no-reflow.
`Covered stents do not decrease the rates of periprocedural myocardial infarction and restenosis. Most available
`evidence supports treatment with drug-eluting stents in this high-risk lesion subset to reduce angiographic and
`clinical restenosis, although large, randomized trials comparing drug-eluting stents and bare-metal stents are
`needed.
`(J Am Coll Cardiol Intv 2011;4:831–43) © 2011 by the American College of Cardiology Foundation
`
`The long-term success of surgical coronary re-
`vascularization is limited by accelerated athero-
`sclerosis and intimal fibrosis of the saphenous
`vein graft (SVG) after its use as a vascular conduit.
`At 1 year, the incidence of 1 or more total SVG
`occlusions has been reported to be as high as 41%
`after on-pump bypass surgery (Table 1) (1–8). Be-
`
`cause of increased morbidity and mortality with
`repeat coronary artery bypass graft surgery, SVG
`intervention is considered by many to be the
`preferred revascularization modality in patients
`with diseased SVGs and accounts for approxi-
`mately 5% to 10% of all percutaneous coronary
`interventions (PCI) (9–14).
`
`From the *University of California–Los Angeles Medical Center, Los
`Angeles, California; †Stanford University Medical Center, Palo Alto,
`California; ‡University of Ulsan College of Medicine, Asan Medical
`Center, Seoul, South Korea; §Piedmont Heart Institute, Atlanta, Geor-
`gia; 储Columbia University Medical Center and the Cardiovascular
`Research Foundation, New York, New York; ¶Veterans Affairs North
`Texas Healthcare System, and University of Texas Southwestern Med-
`ical Center, Dallas, Texas; #Antwerp Cardiovascular Institute Middel-
`heim, AZ Middelheim, Antwerp, Belgium; **Washington Hospital
`Center, Washington, DC; ††Deutsches Herzzentrum, Technische Uni-
`versität, Munich, Germany; and the ‡‡Brigham and Woman’s Hospital,
`Boston, Massachusetts. Dr. Lee has received honoraria from Boston
`Scientific, St. Jude Medical, Daiichi-Sankyo, Bristol-Myers Squibb, and
`Merck. Dr. Park has received consulting fees from Cordis; lecture fees
`from Cordis, Medtronic, and Boston Scientific; and research grants from
`Cordis and Medtronic. Dr. Kandzari has received research/grant support
`from Abbott Vascular, Cordis, and Medtronic Cardiovascular, and
`consulting honoraria from Abbott Vascular and Medtronic. Dr. Kirtane
`has served as a consultant and speaker for Medtronic Cardiovascular,
`
`Abbott Vascular, and Boston Scientific. Dr. Fearon has received a
`research grant from St. Jude Medical. Dr. Brilakis received speaker
`honoraria from St. Jude Medical and Terumo; received research
`support from Abbott Vascular and InfraReDx; and his spouse is an
`employee of Medtronic. Dr. Kim has received lecture fees from
`Cordis. Dr. Waksman received consulting and speaker fees from
`Biotronik, Medtronic, Boston Scientific, and received research grants
`from Biotronik, Boston Scientific, The Medicines Company, Glaxo-
`SmithKline, Schering-Plough, and Sanofi-Aventis. Dr. Mehilli re-
`ceived lecture fees from Abbott and Terumo. Dr. Mauri received
`research grants from Abbott, Cordis, Boston Scientific, Medtronic,
`Bristol-Myers Squibb, Sanofi-Aventis, Eli Lilly, Daiichi Sankyo, and
`consulting fees from Abbott, Cordis, and Medtronic. Dr. Stone is a
`consultant to Abbott Vascular, Boston Scientific, and Medtronic. Dr.
`Vermeersch has reported that he has no relationships relevant to the
`contents of this paper to disclose.
`
`Manuscript received March 11, 2011; revised manuscript received April
`21, 2011, accepted May 14, 2011.
`
`
`Page 1
`
`Teleflex Ex. 2213
`Medtronic v. Teleflex
`
`

`

`832
`
`Lee et al.
`SVG Intervention
`
`J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S , V O L . 4 , N O . 8 , 2 0 1 1
`
`A U G U S T 2 0 1 1 : 8 3 1 – 4 3
`
`In this review, we describe the risk factors for complications
`after SVG intervention and discuss the optimal procedural
`treatment strategies regarding periprocedural anticoagulation,
`choice of stent, and measures to mitigate the risks of distal
`embolization.
`
`Pathobiology of SVG
`
`Abbreviations
`and Acronyms
`
`BMS ⴝ bare-metal stent(s)
`
`CI ⴝ confidence interval
`
`CK-MB ⴝ creatine kinase-
`myocardial band
`
`DES ⴝ drug-eluting stent(s)
`
`FDA ⴝ U.S. Food and Drug
`Administration
`
`SVG intervention remains technically challenging and is asso-
`ciated with higher rates of periprocedural myocardial infarc-
`tion, in-hospital mortality, restenosis, and occlusion compared
`with PCI of native coronary arteries largely because of the
`friable, degenerated atheromatous and thrombotic debris that
`develop when SVGs deteriorate (15). Progression of disease
`outside the stented segment can also lead to high rates of target
`vessel revascularization. Therefore,
`treatment of native coronary artery
`lesions is preferred to treatment of
`degenerated SVG if feasible.
`A recognized consequence of
`SVG intervention is distal emboli-
`zation of atheroembolic debris with
`decreased epicardial and microvas-
`cular perfusion due to capillary
`plugging and vasospasm from the
`release of neurohumoral factors
`such as serotonin. Distal emboliza-
`tion may result in the slow or no-
`reflow phenomenon in approxi-
`mately 10% to 15% of cases and is
`associated with periprocedural an-
`gina and ischemic ST-segment
`changes (16). In such instances,
`subsequent myocardial
`infarction
`occurs in 31% of patients and in-
`hospital mortality increases 10-fold
`(17). However, distal embolization
`remains difficult to predict (18).
`
`FFR ⴝ fractional flow
`reserve
`
`HR ⴝ hazard ratio
`
`MACE ⴝ major adverse
`cardiac event(s)
`
`OR ⴝ odds ratio
`
`PCI ⴝ percutaneous
`coronary intervention
`
`PTFE ⴝ
`polytetrafluorethylene
`
`SVG ⴝ saphenous vein graft
`
`TIMI ⴝ Thrombolysis In
`Myocardial Infarction
`
`Predictors of
`Adverse Clinical Events
`
`Periprocedural creatine kinase-myocardial band (CK-MB)
`elevation after successful SVG intervention was common
`(ranging from 15% to 47%) (19,20). The use of embolic
`protection devices has been systematically associated with
`periprocedural myocardial infarction rates ⬍10% (21,22).
`Differences in myocardial infarction rates between studies
`may also be explained by differences in myocardial infarction
`definitions,
`the sensitivity and frequency of biomarker
`measurement, and the complexity of SVG disease studied.
`Hong et al. (19) reported that 15% of patients experienced
`major CK-MB release exceeding 5⫻ the upper limit of
`normal following SVG PCI. Although the association of
`
`Table 1. Saphenous Vein Graft Occlusion Rates From Selected Studies
`
`Study/First
`Author (Ref. #)
`
`1 Year
`
`5 Years
`
`10 Years
`
`PRAGUE-4 (1)
`
`41 (per patient on-pump)
`
`51 (per patient off-pump)
`
`PREVENT IV (2)
`
`41.7 (per patient)
`
`26.6 (per SVG)
`
`NA
`
`NA
`
`NA
`
`NA
`
`NA
`
`NA
`
`NA
`
`NA
`
`Fitzgibbon et al. (3) 19 (per SVG)
`
`25 (per SVG)
`
`40 (per SVG)
`
`RIGOR (4)
`
`31 (per patient)
`
`19 (per SVG)
`
`Halabi et al. (5)
`
`39.3 (per patient)
`
`Khot et al. (6)
`
`30.1 (SVG)
`
`ROOBY (7)
`
`28.7 (per patient on-pump)
`
`36.5 (per patient off-pump)
`
`NA
`
`NA
`
`NA
`
`NA
`
`NA
`
`NA
`
`NA
`
`NA
`
`NA
`
`NA
`
`NA
`
`NA
`
`Goldman et al. (8)
`
`20 (per patient)
`
`31 (per patient) 39 (per patient)
`
`Values are %.
`NA ⫽ not available; PREVENT IV ⫽ Project of Ex Vivo Vein Graft Engineering via Transfection;
`RIGOR ⫽ Reduction in Graft Occlusion Rates; ROOBY ⫽ Veterans Affairs Randomized On/Off
`Bypass study.
`
`periprocedural myonecrosis and late clinical outcomes is
`controversial among patients undergoing native vessel PCI,
`even minor elevations of CK-MB (1⫻ to 5⫻ normal) after
`SVG intervention have been associated with increased
`mortality at 1 year (6.5% vs. 4.8%, p ⬍ 0.05), with CK-MB
`release exceeding 5⫻ the upper limit of normal increasing
`1-year mortality by 144%. Multivariate analysis revealed
`that major CK-MB release after SVG intervention was a
`powerful independent predictor of late mortality (odds ratio
`[OR]: 3.3, 95% confidence interval [CI]: 1.7 to 6.2).
`Lesion length, greater angiographic degeneration of
`SVGs, and larger estimated plaque volume have been
`identified as predictors of 30-day major adverse cardiac
`events (MACE) after SVG intervention (23–25). This may
`be explained by the fact that the greater the amount of
`plaque, the greater the likelihood of distal embolization
`after intervention, leading to myocardial infarction.
`Patient sex also appears to be a significant predictor of
`outcomes after SVG intervention. Women had higher 30-day
`cumulative mortality rates (4.4% vs. 1.9%, p ⫽ 0.02) compared
`with men (26). Furthermore, women had a higher incidence of
`vascular complications (12% vs. 7.3%, p ⫽ 0.006) and post-
`procedural acute renal failure (8.1% vs. 4%, p ⫽ 0.02).
`In a 172-patient study of SVG intervention with drug-
`eluting stents (DES), chronic renal
`insufficiency (serum
`creatinine ⱖ1.5 mg/dl) was the only significant predictor of
`1-year MACE (hazard ratio [HR]: 2.2, 95% CI: 1.1 to 4.3,
`p ⫽ 0.03) (27). A trend was also present toward higher rates
`of target vessel revascularization in the renal insufficiency
`group (21.8% vs. 10.3%, HR: 2.42, 95% CI: 0.94 to 6.24,
`p ⫽ 0.059). Similar results were observed with bare-metal
`stents (BMS). Overall mortality rates were significantly
`higher in patients with renal insufficiency (p ⬍ 0.001) (28).
`
`
`Page 2
`
`Teleflex Ex. 2213
`Medtronic v. Teleflex
`
`

`

`J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S , V O L . 4 , N O . 8 , 2 0 1 1
`
`A U G U S T 2 0 1 1 : 8 3 1 – 4 3
`
`Lee et al.
`SVG Intervention
`
`833
`
`Decision to Perform
`SVG Percutaneous Intervention
`
`The decision regarding whether or not to intervene in a
`diseased SVG should be guided by the patient’s symptoms,
`angiographic evidence of a significant stenosis, and nonin-
`vasive evidence of myocardial ischemia in the region sub-
`tended by the SVG. Even though the role of intravascular
`ultrasound or fractional flow reserve (FFR) measurement in
`assessing the significance of SVG disease has not been well
`studied, FFR can be performed in an SVG in a similar
`fashion as in a native coronary vessel. The pressure sensor
`should be positioned in the distal two-thirds of the native
`vessel so the entire conduit can be interrogated. Intravenous
`adenosine should be administered to induce hyperemia and
`a slow pullback of the pressure wire can be performed to
`distinguish focal from diffuse disease. Prospective validation
`of an FFR cutoff value of 0.75 to 0.80 to detect hemody-
`namically significant SVG stenosis has not been performed.
`Nonetheless, this cutoff is generally used in clinical practice.
`Of note, however, SVG disease progresses more rapidly
`than native coronary artery disease, and the safety of
`deferring intervention on a diseased SVG with a nonisch-
`emic FFR has not been studied.
`Adverse clinical events occurring ⬎12 months after initial
`SVG intervention most frequently resulted from disease
`progression at untreated intermediate lesions (29). Because
`SVG disease can progress rapidly, some have advocated
`prophylactically stenting intermediate SVG lesions as op-
`posed to continuing with medical therapy alone. In the
`small (57-patient) randomized VELETI (Treatment of
`Moderate Vein Graft Lesions With Paclitaxel Drug-
`Eluting Stents) trial, the 1- and 3-year MACE rates were
`significantly lower in patients in whom moderate (30% to
`60%) SVG stenoses were treated with paclitaxel-eluting
`stents compared with patients who received medical treat-
`ment (3% vs. 19%, p ⫽ 0.09 at 1 year, and 3% vs. 26%, p ⫽
`0.02 at 3 years), thus supporting a strategy of plaque sealing
`with DES in moderate nonangiographically significant le-
`sions in degenerated SVGs at increased risk for disease
`progression and adverse clinical events (30,31). However,
`this trial was an imaging study that was not powered for
`clinical endpoints. The 450-patient VELETI II (Sealing
`Moderate Coronary Saphenous Vein Graft Lesions With
`Paclitaxel-Eluting Stents) trial (NCT01223443) is currently
`randomizing patients with intermediate SVG lesions to
`either SVG intervention with paclitaxel-eluting stents ver-
`sus medical therapy alone and has a primary clinical rather
`than angiographic endpoint.
`
`Treatment of Occluded SVGs
`
`In a study of 34 patients with chronic total SVG occlusion
`for which percutaneous revascularization was attempted,
`
`successful recanalization with stent implantation was low
`(68%) (32). At a median follow-up of 18 months, the rates
`of in-stent restenosis and target vessel revascularization were
`unacceptably high (68% and 61%, respectively) in patients
`who underwent successful stenting despite a high use of
`DES (95%). Given the poor short- and long-term outcomes
`of percutaneous revascularization in chronic total occlusion
`of SVGs, percutaneous revascularization should rarely be
`considered except for acute occlusion in the setting of
`myocardial infarction. Instead, attempts to recanalize the
`native coronary artery are preferred if feasible.
`
`Antithrombin and Antiplatelet Therapy
`
`The preferred parenteral antithrombotic therapy during
`SVG intervention has not been studied in a dedicated,
`prospective clinical trial. Several studies demonstrated that
`the role of glycoprotein IIb/IIIa antagonists in SVG inter-
`vention is limited given their failure to demonstrate a
`reduction in periprocedural myocardial infarction (33–35).
`However, 1 post hoc analysis demonstrated a trend toward
`improved procedural success when glycoprotein IIb/IIIa
`antagonists were used in conjunction with filter-based
`embolic protection (p ⫽ 0.058) but the MACE was not
`different at 30 days (36). In a single center, retrospective
`observational study, bivalirudin was associated with a sig-
`nificant reduction in major CK-MB elevation and a trend
`toward lower in-hospital non–Q-wave myocardial infarc-
`tion, repeat revascularization, and vascular complications
`compared with unfractionated heparin (37). In the subset of
`329 patients who underwent SVG intervention in ACUITY
`(Acute Catheterization and Urgent Intervention Triage
`Strategy Trial) (38), the rates of ischemic bleeding and net
`clinical endpoints were similar with bivalirudin mono-
`therapy, bivalirudin plus a glycoprotein IIb/IIIa antagonist,
`and heparin plus a glycoprotein IIb/IIIa antagonist. Minor
`bleeding complications were lower with bivalirudin alone
`compared with heparin plus a glycoprotein IIb/IIIa antag-
`onist (26% vs. 38%, p ⫽ 0.05). Thus, bivalirudin may offer
`a safety advantage over other antithrombotic regimens, with
`equal or greater suppression of adverse ischemic events,
`although this conclusion is not definitive in the absence of
`an adequately powered randomized trial.
`
`Stent Type Selection
`
`Bare-metal stents. The SAVED (Saphenous Vein de Novo)
`trial reported that compared with balloon angioplasty, BMS
`were associated with higher procedural success (92% vs.
`69%, p ⬍ 0.001), a trend toward a reduction in angiographic
`restenosis (36% vs. 47%, p ⫽ 0.11), and lower MACE
`through 240 days (26% vs. 38%, p ⫽ 0.04) (39). Since the
`SAVED report, the overwhelming majority of SVG inter-
`vention has been performed with stents, and subsequent
`
`
`Page 3
`
`Teleflex Ex. 2213
`Medtronic v. Teleflex
`
`

`

`834
`
`Lee et al.
`SVG Intervention
`
`J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S , V O L . 4 , N O . 8 , 2 0 1 1
`
`A U G U S T 2 0 1 1 : 8 3 1 – 4 3
`
`randomized trials have compared BMS with covered stents
`or DES (Table 2).
`Covered stents. Stents covered with a mesh, most com-
`monly polytetrafluorethylene (PTFE), have a theoretical
`advantage over conventional stents because they may “trap”
`friable atheroemboli and prevent distal embolization and
`serve as a smooth-muscle cell barrier and therefore decrease
`restenosis. However, 3 prospective randomized trials failed
`to demonstrate benefit with covered stents. SYMBIOT III
`(A Prospective, Randomized Trial of a Self-Expanding
`PTFE Stent Graft During SVG Intervention–Late Results)
`(40) compared the self-expandable PTFE-covered nitinol
`Symbiot stent (Boston Scientific Corp., Natick, Massachu-
`setts) with BMS. At 8 months, the incidence of MACE
`between the Symbiot group and BMS was similar (30.6% vs.,
`26.6%, p ⫽ 0.43). A trend toward increased target lesion
`revascularization with the Symbiot stent was also observed
`(23.5% vs. 15.6%, p ⫽ 0.055). The RECOVERS (Randomized
`Evaluation of Polytetrafluoroethylene-Covered Stent in Sa-
`phenous Vein Grafts) trial (41) randomized 301 patients to
`treatment with either the PTFE-covered JoStent balloon-
`expandable stent (Jomed International AB, Helsingborg, Swe-
`den) or BMS. The PTFE group had a higher incidence of
`30-day MACE (10.9% vs. 4.1%, p ⫽ 0.047), mainly attributed
`to increased incidence of myocardial infarction (10.3% vs.
`3.4%, p ⫽ 0.037). At 6 months, the restenosis rate was similar
`between the 2 groups (24.2% vs. 24.8%, p ⫽ 0.237), and the
`MACE rate was not different (23.1% vs. 15.9%, p ⫽ 0.153).
`
`The BARRICADE (Barrier Approach to Restenosis: Restrict
`Intima to Curtail Adverse Events) trial (42) also randomized
`243 patients to treatment with either the PTFE-covered
`JoStent balloon-expandable stent (Jomed) or BMS. At 5-year
`follow-up, target vessel failure was higher in the JoStent group
`than in the BMS group (68.3% vs. 51.8%, p ⫽ 0.007),
`emphasizing the dismal long-term prognosis of SVG treat-
`ment with either BMS or covered stents.
`Two other covered stents have shown promise in the
`treatment of degenerated SVGs although long-term head-
`to-head comparison data with BMS are lacking. In the
`SESAME first
`in human trial (43), 20 patients who
`underwent SVG intervention with a novel nanosynthesized,
`membrane-covered self-expanding superelastic all-metal
`endoprosthesis stent (SESAME stent, Advanced Biopros-
`thetic Surfaces, Ltd., San Antonio, Texas) had a 0% rate of
`MACE at 30 days. At 9 months, the MACE rate was 14%
`(3 patients underwent repeat intervention: 1 underwent
`target lesion revascularization for restenosis at the overlap of
`2 stents and 2 underwent target vessel revascularization for
`lesions outside the stented segment). Preliminary results
`with the MGuard stent (InspireMD, Tel Aviv, Israel), a
`BMS with a polymeric net attached to its surface, demon-
`strated favorable early performance in a study that included
`16 patients who underwent SVG intervention with no
`angiographic/procedural complications, and no adverse
`events up to 30 days (44).
`
`Table 2. Clinical Outcomes of Randomized Stent Trials in Saphenous Vein Grafts
`
`SYMBIOT III
`
`BARRICADE
`
`RECOVERS
`
`SOS
`
`RRISC
`
`ISAR-CABG
`
`PTFE BMS
`
`p Value
`
`PTFE
`
`BMS
`
`p Value
`
`PTFE
`
`BMS
`
`p Value
`
`PES
`
`BMS
`
`p Value
`
`SES
`
`BMS
`
`p Value
`
`DES
`
`BMS
`
`p Value
`
`MACE
`
`1 yr
`
`30.6
`
`26.6
`
`0.43
`
`NA
`
`39.2*
`
`28.0*
`
`60.2
`
`37.0
`
`0.07
`
`0.001
`
`23.1†
`
`15.9†
`
`NA
`
`NA
`
`0.15
`
`NA
`
`37
`
`54
`
`49
`
`77
`
`0.20
`
`0.49
`
`15.8†
`
`29.7†
`
`58
`
`41
`
`0.15
`
`0.13
`
`15.4
`
`NA
`
`22.1
`
`NA
`
`0.03
`
`NA
`
`3 yrs
`
`5 yrs
`
`Death
`
`1 yr
`
`3 yrs
`
`NA
`
`NA
`
`NA
`
`NA
`
`NA
`
`68.3
`
`51.8
`
`0.007
`
`NA
`
`NA
`
`NA
`
`NA
`
`NA
`
`NA
`
`NA
`
`NA
`
`NA
`
`NA
`
`NA
`
`NA
`
`2.6‡
`
`NA
`
`4.7‡
`
`NA
`
`0.29
`
`NA
`
`7.0
`
`18.8
`
`5.0
`
`11.2
`
`0.51
`
`0.13
`
`2.6†
`
`NA
`
`2.8†
`
`NA
`
`0.92
`
`NA
`
`12
`
`24
`
`5
`
`13
`
`0.27
`
`0.19
`
`2.6†
`
`29
`
`0†
`
`0
`
`NA
`
`0.99
`⬍0.001
`
`NA
`
`5.2
`
`NA
`
`NA
`
`4.7
`
`NA
`
`NA
`
`0.82
`
`NA
`
`NA
`
`5 yrs
`
`NA
`
`NA
`
`NA
`
`29.8
`
`22.3
`
`0.20
`
`NA
`
`NA
`
`NA
`
`NA
`
`NA
`
`NA
`
`NA
`
`MI
`
`1 yr
`
`3 yrs
`
`9.2
`
`NA
`
`10.9
`
`NA
`
`0.61
`
`NA
`
`14.2
`
`21.0
`
`11.3
`
`14.1
`
`0.53
`
`0.21
`
`0.16
`
`14.1†
`
`5.5†
`
`NA
`
`NA
`
`NA
`
`NA
`
`0.02
`
`NA
`
`NA
`
`15
`
`17
`
`NA
`
`31
`
`46
`
`NA
`
`0.10
`
`0.01
`
`NA
`
`2.6†
`
`18
`
`NA
`
`0†
`
`5
`
`NA
`
`0.99
`
`0.15
`
`NA
`
`4.2
`
`NA
`
`NA
`
`6.0
`
`NA
`
`NA
`
`0.27
`
`NA
`
`NA
`
`5 yrs
`
`NA
`
`NA
`
`NA
`
`26.2
`
`17.4
`
`TLR
`
`1 yr
`
`3 yrs
`
`5 yrs
`
`23.5
`
`15.6
`
`NA
`
`NA
`
`NA
`
`NA
`
`0.06
`
`NA
`
`NA
`
`28.2
`
`37.4
`
`43.9
`
`21.1
`
`21.8
`
`29.6
`
`0.46
`
`0.02
`
`0.04
`
`9.6†
`
`8.3†
`
`NA
`
`NA
`
`NA
`
`NA
`
`0.84
`
`NA
`
`NA
`
`5
`
`10
`
`NA
`
`28
`
`41
`
`NA
`
`0.003
`
`0.004
`
`NA
`
`5.3†
`
`21.6†
`
`24
`
`NA
`
`30
`
`NA
`
`0.05
`
`0.55
`
`NA
`
`7.2
`
`NA
`
`NA
`
`13.1
`
`NA
`
`NA
`
`0.02
`
`NA
`
`NA
`
`*Target vessel failure (composite of all-cause death, MI, or clinically driven target vessel revascularization). †6 months. ‡Cardiac death.
`BARRICADE ⫽ Barrier Approach to Restenosis: Restrict Intima to Curtail Adverse Events study; BMS ⫽ bare-metal stent(s); DES ⫽ drug-eluting stent(s); ISAR-CABG ⫽ Prospective, Randomized Trial of
`Drug-Eluting Stents Versus Bare Metal Stents for the Reduction of Restenosis in Bypass Grafts; MACE ⫽ major adverse cardiac event(s); MI ⫽ myocardial infarction; NA ⫽ not available; PTFE ⫽
`polytetrafluorethylene; RECOVERS ⫽ Randomized Evaluation of Polytetrafluoroethylene-Covered Stent in Saphenous Vein Grafts; RRISC ⫽ Reduction of Restenosis in Saphenous Vein Grafts With
`Cypher Sirolimus-Eluting Stent; SOS ⫽ Stenting of Saphenous Vein Grafts; SYMBIOT III ⫽ A Prospective, Randomized Trial of a Self-Expanding PTFE Stent Graft During SVG Intervention–Late Results;
`TLR ⫽ target lesion revascularization.
`
`
`Page 4
`
`Teleflex Ex. 2213
`Medtronic v. Teleflex
`
`

`

`J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S , V O L . 4 , N O . 8 , 2 0 1 1
`
`A U G U S T 2 0 1 1 : 8 3 1 – 4 3
`
`Lee et al.
`SVG Intervention
`
`835
`
`Drug-eluting stents. The RRISC (Reduction of Restenosis
`in Saphenous Vein Grafts With Cypher Sirolimus-Eluting
`Stent) trial (21), which included 75 patients, reported that
`sirolimus-eluting stents (Cordis, Warren, New Jersey) re-
`duced late loss, the binary restenosis rate, and target lesion
`and vessel
`revascularization compared with BMS at
`6-month follow-up. However, the DELAYED RRISC
`(Death and Events at Long-Term Follow-Up Analysis:
`Extended Duration of the Reduction of Restenosis in
`Saphenous Vein Grafts With Cypher Stent) study (45),
`which was a post hoc analysis of RRISC trial at 3 years,
`reported similar rates of target vessel revascularization.
`Although statistically underpowered for clinical outcomes,
`significantly higher all-cause mortality at 3 years was re-
`ported with sirolimus-eluting stents compared with BMS.
`The SOS (Stenting of Saphenous Vein Grafts) trial (22),
`which included 80 patients randomized to either paclitaxel-
`eluting stents (Taxus, Boston Scientific Corp., Maple
`Grove, Minnesota) or BMS, demonstrated a significant
`reduction in MACE driven by lower target lesion revascu-
`larization rates with paclitaxel-eluting stents without in-
`creased death or myocardial infarction through nearly 3-year
`follow-up (46). The primary endpoint of these 2 small trials
`was angiographic restenosis, and the results showed similar
`angiographic restenosis rates at 6- (RRISC) and 12-month
`(SOS)
`follow-up but higher mortality at
`long-term
`follow-up in the RRISC trial. ISAR-CABG (Prospective,
`Randomized Trial of Drug-Eluting Stents Versus Bare
`Metal Stents for the Reduction of Restenosis in Bypass
`Grafts), which randomized 610 patients with diseased SVGs
`to DES and BMS, the primary endpoint of MACE at 1-year
`post index PCI was lower in the DES group than in the BMS
`group (15.4% vs. 22.1%, p ⫽ 0.03) and was mainly driven by
`a nearly 50% relative reduction in the risk of target lesion
`revascularization (7.2% vs. 13.1%, p ⫽ 0.02), with nonsignif-
`icant differences in mortality (47).
`A meta-analysis comparing DES with BMS in SVG
`intervention (which also included nonrandomized studies)
`has also reported lower mortality, MACE, target lesion
`revascularization, and target vessel revascularization without
`increased risk of myocardial infarction or stent thrombosis
`(48). Eight other meta-analyses comparing DES with BMS
`in SVG intervention have demonstrated consistent results of
`improved efficacy with DES and no significant safety hazard
`(48–55).
`Two ongoing trials are comparing DES with BMS in
`SVGs: 1) BASKETSAVAGE (Basel Stent Kosten Effek-
`tivitäts Trial–Saphenous Venous Graft Angioplasty Using
`Glycoprotein IIb/IIIa Receptor Inhibitors and Drug-
`Eluting Stents) (NCT00595647); and 2) the Veterans’
`Affairs Cooperative Study #571, DIVA (Drug Eluting
`Stents Versus Bare-Metal Stents in Saphenous Vein Graft
`Angioplasty) trials (NCT01121224).
`
`Choice of DES in SVG. In a multicenter analysis of 172
`real-world patients comparing first-generation DES, SVG
`intervention with sirolimus- and paclitaxel-eluting stents
`resulted in nonsignificant differences in survival (HR: 1.28,
`95% CI: 0.39 to 4.25, p ⫽ 0.69) and target vessel revascu-
`larization (HR: 2.54, 95% CI: 0.84 to 7.72, p ⫽ 0.09) (56).
`Outcomes comparing second-generation stents in SVG
`intervention are not yet available; the SOS-Xience V (Pro-
`spective Evaluation of the Xience V Everolimus-Eluting
`Stent in Saphenous Vein Graft Atherosclerosis: The Stent-
`ing of Saphenous Vein Grafts Xience V Angiographic
`Study) (NCT00911976) will provide initial results with the
`everolimus-eluting stent in 2011.
`
`SVG Intervention Technique
`
`Pre-dilation versus direct stenting. As opposed to pre-
`dilation with balloon angioplasty, direct stenting has the
`potential benefit of trapping debris and decreasing distal
`embolization that may occur from repeated balloon infla-
`tions. In a registry of unselected patients who underwent
`SVG intervention, direct stenting was associated with a
`nearly 50% reduction in CK-MB elevations greater than 4⫻
`normal (13.6% vs. 23%, p ⬍ 0.12), overall lower maximum
`CK-MB release (9.5 vs. 19.6, p ⬍ 0.001), and fewer
`non–Q-wave myocardial infarctions (10.7% vs. 18.4%, p ⬍
`0.02) (57). A prospective randomized trial is needed to
`determine whether pre-dilation versus direct stenting is
`effective in reducing distal embolization.
`Small stent diameter. In a study of 209 SVG lesions treated
`with DES, Hong et al. (58) examined the outcomes of 3
`groups according to the ratio of the stent diameter to the
`average intravascular ultrasound reference lumen diameter
`(group I: ⬍0.89, group II: 0.9 to 1.0, and group III: ⬎1.0).
`Plaque intrusion volume as defined as the amount of tissue
`extrusion through the stent struts after SVG intervention
`was smallest in group I (group I: 0.25 ⫾ 0.68 mm3, group II:
`0.40 ⫾ 0.68 mm3, and group III: 0.75 ⫾ 1.34 mm3; p⫽ 0.007).
`The incidence of CK-MB elevation ⬎3⫻ normal was 6% in
`group I, 9% in group II, and 19% in group III (p ⫽ 0.03)
`without an increase in clinical events at 1 year. The
`incidence of 1-year target lesion revascularization (group I:
`13%, group II: 9%, and group III: 15%; p ⫽ 0.5) and target
`vessel revascularization (group I: 13%, group II: 13%, and
`group III: 15%; p ⫽ 0.9) was similar. While the concept of
`undersized stent selection to reduce distal embolization is
`intriguing, such a method must be balanced by theoretically
`possibly higher rates of restenosis and stent thrombosis.
`Therefore, a prospective, randomized study is required to
`confirm the theoretical benefits of this technique.
`Embolic protection devices. Distal embolization is common
`in SVG interventions. Particulate debris has been retrieved
`from as many as 91% of distal embolic protection devices
`(59). Despite the class I American College of Cardiology/
`
`
`Page 5
`
`Teleflex Ex. 2213
`Medtronic v. Teleflex
`
`

`

`836
`
`Lee et al.
`SVG Intervention
`
`J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S , V O L . 4 , N O . 8 , 2 0 1 1
`
`A U G U S T 2 0 1 1 : 8 3 1 – 4 3
`
`Table 3. Comparison of Different Embolic Protection Devices
`
`Distal
`Balloon
`Occlusion
`
`Proximal
`Balloon
`Occlusion
`
`Distal Filter
`
`Complete occlusion
`
`Allows perfusion
`
`Ischemia
`
`Maintenance of antegrade blood flow
`during intervention
`
`Protects before crossing lesion
`
`No
`
`Yes
`
`No
`
`Yes
`
`No
`
`Yes
`
`No
`
`Yes
`
`No
`
`No
`
`Crossing profile
`
`Maneuverability
`
`Ease of use
`
`High (3.2-F)*
`
`Low (2.7)†
`
`Reduced
`
`Simple
`
`Good
`
`Good
`
`Complex
`
`Complex
`
`Yes
`
`No
`
`Yes
`
`No
`
`Yes
`
`NA
`
`loon deflation and restoration of antegrade blood flow.
`Several advantages are the low crossing profile and
`entrapment of debris of all sizes as well as neurohumoral
`mediators such as serotonin and thromboxane that may
`have an adverse effect on the distal microvasculature. Its
`disadvantages are: 1) the need to cross the lesion before
`adequate protection, possibly liberating friable material
`before balloon occlusion; 2) temporary cessation of blood
`flow leading to ischemia and possible hemodynamic
`instability, as well as limiting visualization making accu-
`rate stent placement difficult; 3) inability to obtain full
`evacuation, especially near the occlusion balloon; and 4)
`possible traumatic injury to the SVG during balloon
`occlusion. Distal
`lesions are not amenable to distal
`balloon occlusion devices because a relatively disease-free
`landing zone of approximately 3 cm distal to the lesion is
`required for placement of the occlusion balloon.
`The Food and Drug Administration (FDA)–approved
`PercuSurge GuardWire (Medtronic, Minneapolis, Min-
`nesota) consists of a 0.014-inch diameter wire with a
`central
`lumen affixed to an inflatable distal occlusion
`balloon (Fig. 2, Table 4). SAFER (Saphenous Vein Graft
`Angioplasty Free of Emboli, Randomized Trial) (20)
`demonstrated that it decreased the incidence of no-reflow
`(3.2% vs. 8.3%, p ⫽ 0.005) and 30-day MACE (9.6% vs.
`16.5%, p ⫽ 0.004).
`The TriActiv embolic protection system (Kensey Nash
`Corporation, Exton, Pennsylvania) differs from the Guard-
`Wire in that it has a flush catheter, which infuses heparin-
`ized saline, attached to the balloon guidewire. The mixture
`of saline, blood, and atheromatous debris is extracted
`through the guiding catheter. PRIDE (A Prospective, Ran-
`domized Controlled Trial of Distal Protection With the
`
`Capture of smaller particles
`
`Capture of neurohormonal substances
`
`No
`
`No
`
`Yes
`
`Yes
`
`Yes
`
`Yes
`
`*FilterWire EZ (Boston Scientific). †PercuSurge GuardWire (Medtronic).
`NA ⫽ not available.
`
`American Heart Association PCI guidelines’ recommenda-
`tion for the use of embolic protection devices in SVG
`intervention, overall adoption remains low (60). In the
`American College of Cardiology National Cardiovascular
`Data CathPCI Registry, embolic protection was only used
`in 23% of patients (10). Currently available embolic protec-
`tion devices include occlusion balloon plus aspiration sys-
`tems, distal filter-based devices, and proximal flow interrup-
`tion catheters (Table 3) (61).
`Distal balloon occlusion devices. Distal balloon occlusion
`of the SVG beyond the lesion creates a stagnant column
`of blood that may prevent plaque embolization into the
`myocardial bed (Fig. 1). Upon the conclusion of the
`intervention, the blood with contained debris can be
`removed by an aspiration catheter before occlusion bal-
`
`Figure 1. Distal Balloon Occlusion Device
`
`(A) The lesion is crossed with the GuardWire. (B) GuardWire balloon inflated and percutaneous coronary intervention performed under distal protection.
`(C) Thereafter, the balloon is inflated until angiography shows no forward flow. Saphenous vein graft (SVG) intervention can be performed with complete
`distal protection. Image provided courtesy of Medtronic. ©2011 Medtronic or its affiliates. All rights reserved.
`
`
`Page 6
`
`Teleflex Ex. 2213
`Medtronic v. Teleflex
`
`

`

`J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S , V O L . 4 , N O . 8 , 2 0 1 1
`
`A U G U S T 2 0 1 1 : 8 3 1 – 4 3
`
`Lee et al.
`SVG Intervention
`
`837
`
`Figure 2. PercuSurge GuardWire Distal Protection System
`
`(A) A Microseal adapter controls a miniature valve within the hypotube and keeps the occlusion balloon inflated while standard interventional devices such as
`balloons and stents are passed over the wire to perform percutaneous coronary intervention. A 0.014-inch nitinol-based hypotube guidewire in

This document is available on Docket Alarm but you must sign up to view it.


Or .

Accessing this document will incur an additional charge of $.

After purchase, you can access this document again without charge.

Accept $ Charge
throbber

Still Working On It

This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.

Give it another minute or two to complete, and then try the refresh button.

throbber

A few More Minutes ... Still Working

It can take up to 5 minutes for us to download a document if the court servers are running slowly.

Thank you for your continued patience.

This document could not be displayed.

We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.

Your account does not support viewing this document.

You need a Paid Account to view this document. Click here to change your account type.

Your account does not support viewing this document.

Set your membership status to view this document.

With a Docket Alarm membership, you'll get a whole lot more, including:

  • Up-to-date information for this case.
  • Email alerts whenever there is an update.
  • Full text search for other cases.
  • Get email alerts whenever a new case matches your search.

Become a Member

One Moment Please

The filing “” is large (MB) and is being downloaded.

Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.

Your document is on its way!

If you do not receive the document in five minutes, contact support at support@docketalarm.com.

Sealed Document

We are unable to display this document, it may be under a court ordered seal.

If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.


Access Government Site

We are redirecting you
to a mobile optimized page.





Document Unreadable or Corrupt

Refresh this Document
Go to the Docket

We are unable to display this document.

Refresh this Document
Go to the Docket