Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3720_Библиотеки_им_академика_М_И_Перельмана
.pdf
The Spectrum of Clinical Presentations and Management Options Chapter | 26 385
https://t.me/med1917
as vessel size and tortuosi ty, absence of adequate nondiseased landing zone with filter wires, and lack of antegrade flow
when occlusion balloons are applied.
Whereas randomized controlled trials have demonstrated the efficacy of EPDs, the routine use of these devices for SVG
intervention continues to be debated.
Thus, although randomized controlled trials have demonstrated the efficacy of EPDs, their routine use remains
controversial.
THROMBECTOMY DEVICES
Direct thrombectomy devices are classified based on their mechanism of action (see detailed description in Chapter 18).
Thrombectomy devices have shown benefit in terms of surrogate end points such as angiographic TIMI flow, infarct size
reduction, ST-segment resolution, and biomarker analysis [52]. However, in reality, the standard aspiration catheters are
frequently incapable of completely removing the targeted thrombus and are markedly ineffective in managing large
thrombi [53]. Experience has shown that the heavier and more diffusely distributed the thrombus burden in an SVG (and
native coronary arteries alike), the higher the yield of the power-based mechanical extraction thrombectomy devices
[52,54,55]. This is especially relevant in patients who develop SVG stent thrombosis [56], as these cases are commonly
associated with formation of a heavy thrombus load as demonstrated in Fig. 26.6.
A revascularization strategy of distal embolization protection combined with mechanical rheolytic thrombectomy
(AngioJet) has been found useful in SVGs occluded by a large thrombus burden [57]. In challenging cases in which the
SVG intervention requires thrombus clearance and concomitant removal of a significant underlying plaque to facilitate
stent delivery and deployment, the application of a debulking device capable of performing this dual task should be
considered. An example of such proven technology is the excimer laser [58] as shown in Fig. 26.7.
STENTS IN SAPHENOUS VEIN GRAFT INTERVENTIONS
Contemporary revascularization management of SVG includes stenting as an essential element required for safe and
efficacious completion of these interventions. Overall, decisions concerning revascularization in degenerative SVG disease
should be guided by clinical symptoms, angiographic evidence of significant stenosis, the burden of thrombus in the graft,
and evidence of myocardial ischemia [59,60]. Based on these parameters interventionalists can tailor an initial treatment
strategy, which ultimately is completed with appropriate stenting. Figs. 26.8 and 26.9 relate to exemplary cases representing this process.
In consideration of the complex pathology of SVG disease, whereby atherothrombotic lesions tend to rapidly progress,
the possible need for stenting of intermediate SVG stenoses was investigated in a small cohort of 57 patients [61] who
enrolled in the randomized trial VELETI (Treatment of Moderate Vein Graft Lesions With Paclitaxel-Eluting Stents),
(A)
(B) (C)
FIGURE 26.6 Severe degenerative atherothrombotic saphenous vein graft (SVG) disease in a patient with acute coronary syndrome. (A) The
20-year-old graft contains a tight eccentric plaque (upper red circle) followed by severe restenosis and thrombosis of a 7-year-old SVG (lower red
circle). (B) A 5-Fr rapid-exchange rheolytic thrombectomy (AngioJet) catheter (marked by yellow arrow) is advanced onto the SVG, performing a
slow antegrade and retrograde thrombectomy. This results in sign ificant thrombus burden removal a nd marked clinical improvement. (C) Final
angiographic a ppearance of the targeted SVG after adjunct balloon dilatations and stenting, demonstrating marked patency and no residual thrombus or
stenosis. Courtesy of the book editor.
386 Cardiovascular Thrombus
https://t.me/med1917
(C) (D)
(B)(A)
FIGURE 26.7 (A) An elderly patient presented with unstable angina pectoris and ischemia due to the development of a severe atherothrombotic plaque
localized at the distal segment of a 9-year-old saphenous vein graft (SVG) to the obtuse marginal branch (red circle). (B) A 0.9-mm X-80 excimer laser
was advanced to the SVG lesion for targeted plaque debulking and thrombus removal (yellow arrow). (C) The laser emission created a “pilot channel”
(red circle), which enabled safe delivery and adequate positioning of a stent. (D) Final angiographic results after drug-eluting stent deployment. Adequate
distal flow and complete clinical recovery were achieved. Courtesy of the book editor.
although this study was not powered for clinical end points. The results demonstrated that the 1- and 3-year MACE rates
were significantly lower in patients in whom moderate (30%e60%) SVG lesions were treated with paclitaxel-eluting stents
compared with patients who received medical treatment (3% vs. 19%, respectively, P < .09 at 1 year, and 3% vs. 26%,
respectively, P ¼ .02 at 3 years). These findings denote a potential strategy of plaque sealing with a DES for moderate
lesions (angiography based) in SVGs that are deemed to be at increased risk for disease progression and adverse clinical
events if treated with pharmacotherapy only. The VELETI II (Sealing Moderate Coronary Saphenous Vein Graft
Lesions With Paclitaxel-Eluting Stents) trial [62] randomized 125 patients (limited by enrollment of only 28% of the
originally planned 450 patients) with intermediate SVG lesions to either paclitaxel-eluting stents or medical therapy alone.
The Spectrum of Clinical Presentations and Management Options Chapter | 26 387
https://t.me/med1917
(A) (B) (C)
FIGURE 26.8 An 82-year-old patient who underwent coronary artery bypass graft surgery 15 years earlier presented with non-ST-segment elevation
myocardial infarction and significant troponin rise. (A) Selective angiogram of the saphenous vein graft (SVG) to the obtuse marginal branch of the
circumflex artery demonstrating acute total thrombotic occlusion (red circle). (B) Angiographic appearance of the SVG following guidewire crossing of
the occlusion and initial balloon dilatation at the total occlusion. The proximal segment of the graft (marked by two red circles) exhibits large multilayer
and globular thrombi, respectively, while the middle distal segment contains long and diffuse layers of thrombus (yellow arrows). (C) Final angiogram
demonstrating patency of the SVG with mild residual thrombus. Accordingly, postepercutaneous coronary intervention the patient was placed on
intravenous glycoprotein IIb/IIIa receptor antagonist for 4 h and recovered clinically. Courtesy of Scott Willis MD, FACC, Interventional Cardiologist,
Charles George Veterans Affairs Medical Center, Asheville, NC, United States.
The primary end point was the combined incidence of MACEs as recorded by a composite of cardiac death, MI, and
SVG-related revascularization following a period of at least 2 years. No differences were observed between the two
treatment arms at a median follow-up of 3.4 years [63]. Because of the poor short- and long-term outcomes of percutaneous
revascularization in chronic total occlusions (CTOs) of SVGs, it should be considered only in acute occlusion in the setting
of MI or for select patients with unstable angina who require recanalization of a CTO in an SVG, using a unique technique
termed “SVG sculpturing” [64], which utilizes administration of intragraft tissue plasminogen activator and meticulous
thrombus removal by mechanical thrombectomy follow ed by stenting. However, there is a growing trend among
(A) (B) (C)
FIGURE 26.9 A 69-year-old patient underwent coronary artery bypass graft surgery on four vessels 11 years earlier. Over the years, the patient un-
derwent six percutaneous coronary intervention on the saphenous vein grafts (SVGs) and eventually two of the SVGs developed complete occlusion. The
index presentation was the development of non-ST-segment elevation myocardial infarction. The left-ventricular ejection fraction was 45% and the LIMA
was patent to the left anterior descending artery. (A) The SVG to the PDA (the sole remaining SVG) exhibited markedly slow antegrade flow and
contained 99% plaque stenosis (upper red circle). Plaque rupture with very high thrombus burden was noted more distally (lower red circle). (B) Direct
stenting of the targeted graft was performed with administration of direct thrombin inhibitor and implantation of four stents: proximally a 4.0 38-mm
drug-eluting stent (DES; Xience Xpedition, Abbott Vascular), in the middle portion a 4.0 28-mm DES (Xience Alpine), in the middle distal segment a
4.0 18-mm DES (Xience Alpine), and more distally a bare metal stent (Veriflex, Boston Scientific), 4.5 16 mm. (C) Final angiographic appearance
demonstrating adequate patency of the SVG and restoration of adequate antegrade flow. The patient made a clinical recovery. PDA, Posterior Descending
Artery; LIMA, Left Internal Mammary Artery. Courtesy of Kristine Owen MD, FACC, Director, Cardiac Catheterization Laboratory, Charles George
Veterans Affairs Medical Center, Asheville, NC, United States.
388 Cardiovascular Thrombus
https://t.me/med1917
interventionalists to prefer when feasible to recanalize the diseased recipient native coronary artery instead of performing
targeted revascularization of CTO in an SVG [59,65],
Interestingly, PCI in SVGs is associated with a delayed (>12 months) restenosis compared with PCI in native coronary
arteries [66]. A controversy exists as to the preferred stent platform that shoul d be used in SVG interventions. In the
SAVED (Saphenous Vein de Novo) trial BMSs were associated with higher procedural success than balloon angioplasty
(92% vs. 69%, respectively, P ¼ .001), a trend toward reduction of angiographic restenosis (36% vs. 47%, P ¼ .11), and
lower MACE rate through 240 days (26% vs. 38%, P ¼ .04) [60]. Notably, most pivotal coronary DES trials excluded
SVG patients from randomization and some regulatory authorities even consider DES implantation in SVG an off-label
indication [66]. The rationale behind the latter view relates to the larger size of vein grafts, the potential lower benefit
of the DES, and a need to avoid high-pressure balloon inflations during stent deployment. The last relates to the risk of
distal microembolizations due to incomplete apposition of stents in large SVGs [66]. Sbarzaglia and colleagues reported a
registry of 127 DES recipients who were compared with 131 BMS patients treated for SVG stenosis [41]. At 2 years there
were no statistical differences in death (8.7 vs. 7.8%), MI (6.3 vs. 9.4%), or TVR (19.7 vs. 24.2%) between DES and BMS,
respectively. In the large registry STENT (Strategic Transcatheter Evaluation of New Therapies) [41] 820 DES patients
were compared with 348 BMS recipients. At 9-month follow-up the DES was associated with fewer MACEs (14 vs. 21%;
P ¼ .001) and lower rate of composite of death or MI (8.7 vs. 14%; P ¼ .006) and TVR (hazard ratio [HR] 0.36;
P < .001). At 2 years, DES was associated with a lower incidence of death, but the composite of death and MI and the
benefit in reducing TVR and stent thrombosis as recorded at 9-month follow-up were no longer present. Following
adjustment for baseline clinical differences, DES was demonstrated to be accompanied by a significant reduction in 2-year
TVR (HR 0.31, 95% confidence interval [CI] 0.14e 0.66; P ¼ .002). Nevertheless, the registry’s BMS group had more
emergent procedures, e.g., approximately twice as many ST-segment elevation MIs, larger vein graft diameter (3.7 vs.
3.3 mm; P ¼ .001), and more no reflow (6.9 vs. 3.3%; P ¼ .003) compared with the DES group [41]. The randomized trial
RRISC (Reduction of Restenosis in Saphenous Vein Grafts with Cypher Sirolimus-Eluting Stent) [67] compared DES
(sirolimus eluting) with BMS in SVG PCI. At 6-month angiog raphic follow-up significantly lower TVR and restenosis
rates were recognized among the DES patients (14% vs. 33%, P ¼ .03, and 5% vs. 27%, P ¼ .01, respectively). However,
at 32 months, a late “catch-up” phenomenon was observed as the TVR rates were similar between these two stent types
(34% vs. 38%; P ¼ NS).
Gao and coinvestigators analyzed the overall benefits and risks of DES versus BMS in revascularization of diseased
SVG based on data from randomized controlled trials. Accordingly, Figs. 26.10, 26.11, 26.12, and 26.13 correspond to this
analysis.
With DES utilization there was a nonsignificant trend toward reduction in long-term MA CE (RR 0.73; 95% CI
0.47e1.13; P ¼ .163), with substantial heterogeneity in the analyzed trials. DES significantly reduced the risk of shortterm MACE compared with BMS (RR 0.62; 95% CI 0.42e0.92; P ¼ .018), without evidence of heterogeneity [68].
Accordingly, Fig. 26.14 displays the clinical outcomes of several randomized stent trials in SVGs.
Overall, until recently, a common consensus held that while DESs in SVG interventions improve short-term outcome in
comparison with BMSs, this was achieved primarily by reducing TVR for in-stent restenosis. Thus, these stents do not
appear to have an impact on the incidence of long-term MACE, MI, mortality, cardiac death, and stent thrombosis.
However, this view has been challenged. Guttman and coauthors obtained data from a prospective database of 657 patients
who underwent SVG PCI between 2003 and 2011, comparing 344 BMS with 313 DES recipients [69]. A very significant
difference in MACE (defined as all-cause mortality, MI, TVR, and stroke at a median of 3.3 years) in favor of DES (17.9%
Study Year of
BASKET [25]
RRISC [26-28]
SOS [29,30]
ISAR-CABG [14]
MACE: major cardiovascular event; MI: myocardial infarction; TVR: target vessel revascularization; TVF: target vessel failure; TLR: target lesion revascularization
FIGURE 26.10 Display of data on the baseline characteristics of drug-eluting stents (DES) versus bare metal stents (BMS) in four randomized controlled
trials of revascularization of diseased saphenous vein grafts (SVGD). From Gao J, Ren M, Liu Y, Gao M, Sun B. Drug-eluting versus bare metal stent in
treatment of patients with saphenous vein graft disease: a meta-analysis of randomized controlled trials. Int J Cardiol 2016;222:95e100 and Patel PM,
Kern MJ. PCI in failing saphenous vein grafts: DES trumps BMS for the older patient. Cath Cardiovasc Interv 2016;87:50e1 with permission.
publication
2009
2006
2009
2011
Country
Switzerland
Belgium
USA
Germany
Age Sample size
DES BMS Total
71.0
34
13
72.5
38
37
66.5
41
303
39
307
71.5
47
75
80
610
Disease
SVGD
SVGD
SVGD
SVGD
Outcomes
MACE, cardiac death, MI, and TVR
MACE, mortality, MI, TLR, TVF, and TVR
MACE, mortality, MI, TVR, TLR, and TVF
MACE, mortality, MI, stent thrombosis, TLR, TVR
Definition of MACE Jadad
Cardiac death, MI, and
symptom-driven TVR
Death, nonfatal MI, and TVR
Death, MI, TVR and TLR
Death, MI, and TLR
score
4
4
4
5
The Spectrum of Clinical Presentations and Management Options Chapter | 26 389
https://t.me/med1917
Study
long–term
BASKET
RRISC
SOS
ISAR–CABG
Subtotal
short–term
RRISC
SOS
ISAR–CABG
Subtotal
.3 1
Risk ratio
5
Risk ratio
(95% CI)
0.33 ( 0.15, 0.74)
1.43 ( 0.89, 2.30)
0.70 ( 0.50, 0.97)
0.68 ( 0.48, 0.96)
0.73 ( 0.47, 1.13); P=0.163
(I-square: 74.2%; P=0.009)
0.53 ( 0.22, 1.29)
0.75 ( 0.45, 1.26)
0.45 ( 0.20, 1.02)
0.62 ( 0.42, 0.92); P=0.018
(I-square: 0.0%; P=0.518)
FIGURE 26.11 Association of drug-eluting stent utilization and major adverse cardiac events. From Gao J, Ren M, Liu Y, Gao M, Sun B. Drug-eluting
versus bare metal stent in treatment of patients with saphenous vein graft disease: a meta-analysis of randomized controlled trials. Int J Cardiol
2016;222:95e100 and Patel PM, Kern MJ. PCI in failing saphenous vein grafts: DES trumps BMS for the older patient. Cath Cardiovasc Interv
2016;87:50e1 with permission.
Study
long–term
BASKET
RRISC
SOS
ISAR–CABG
Subtotal
short–term
RRISC
SOS
ISAR–CABG
Subtotal
Risk ratio
(95% CI)
2.00 ( 0.10, 39.08)
3.41 ( 0.76, 15.35)
0.37 ( 0.17, 0.79)
0.68 ( 0.33, 1.38)
0.82 ( 0.34, 2.03); P=0.675
(I-square: 59.8%; P=0.058)
2.92 ( 0.32, 26.83)
0.48 ( 0.20, 1.14)
0.43 ( 0.17, 1.12)
0.55 ( 0.27, 1.14); P=0.106
(I-square: 20.6%; P=0.284)
FIGURE 26.12 Association of myocardial infarction as a complication of drug-eluting stent implantation. From Gao J, Ren M, Liu Y, Gao M, Sun B.
Drug-eluting versus bare metal stent in treatment of patients with saphenous vein graft disease: a meta-analysis of randomized controlled trials. Int J
Cardiol 2016;222:95e100 and Patel PM, Kern MJ. PCI in failing saphenous vein grafts: DES trumps BMS for the older patient. Cath Cardiovasc Interv
2016;87:50e1 with permission.
DES vs. 31.2% BMS, P ¼ .0017) was identified over the 5-year follow-up, which was driven by increased TVR in the
BMS group. There was no difference between the groups in death, MI, or stroke. Adjusted Cox analysis confirmed a
decreased risk of MACE for DES compared with BMS (HR 0.75, 95% CI 0.52e0.94), with no difference in the hazard of
all-cause mortality (HR 1.08, 95% CI 0.77e1.68). When the data were analyzed for stents with diameter greater than
4 mm, no difference was found in MACE rates between the two stent types. Moreover, the results of another landmark
investigation appear to be set to carry major implications on the choice of stent selection in SVG PCI. Brennan and
coinvestigators [70] conducted extensive research with specific focus on the challenging group of the elderly who undergo
SVG PCI, since these patients carry even a greater risk than younger patients for complications and increased short- and
long-term MACE rate. Obtaining clinical records from the National Cardiovascular Data Registry CathPCI Registry, the
investigators identified 49,325 older (65 years) individuals who underwent SVG stenting between 2005 and 2009. These
.3 1
Risk ratio
5
390 Cardiovascular Thrombus
https://t.me/med1917
Study
long–term
RRISC
SOS
ISAR–CABG
Subtotal
short–term
RRISC
SOS
ISAR–CABG
Subtotal
.3 1
Risk ratio
5
Risk ratio
(95% CI)
22.41 ( 1.37, 367.04)
1.90 ( 0.71, 5.07)
1.09 ( 0.53, 2.21)
1.98 ( 0.65, 5.98); P=0.227
(I-square: 61.7%; P=0.073)
2.92 ( 0.12, 69.54)
2.38 ( 0.49, 11.55)
0.68 ( 0.11, 4.01)
1.50 ( 0.50, 4.54); P=0.473
(I-square: 0.0%; P=0.531)
FIGURE 26.13 Association of mortality with drug-eluting stent implantation. From Gao J, Ren M, Liu Y, Gao M, Sun B. Drug-eluting versus bare
metal stent in treatment of patients with saphenous vein graft disease: a meta-analysis of randomized controlled trials. Int J Cardiol 2016;222:95e100
and Patel PM, Kern MJ. PCI in failing saphenous vein grafts: DES trumps BMS for the older patient. Cath Cardiovasc Interv 2016;87:50e1 with
permission.
records were linked to Medicare claims to create a longitudinal record. Death, MI, and urgent revascularization with DES
versus BMS were evaluated up to 3 years using propensity matching. Results were stratified by clinical presentation (ACS,
non-ACS), previous lesion treatment (in stent, de novo), and graft segment (aortic, body, distal anastomosis). The results
demonstrated that in the elderly (median age 75 years), acute presentations were prevalent (ACS in 69%; TIMI flow >3in
45%), and adverse clinical outcomes were common by 3 years (death 24.5%; MI 14.6%; urgent revascularization 29.5%) .
Clinical Outcomes of Randomized Stent Trials in Saphenous Vein Grafts
SYMBIOT III
BMS p Value PTFE BMS p Value PTFE BMS p Value PES BMS p Value SES BMS p Value DES BMS p Value
PTFE
MACE
1 yr
30.6 26.6 0.43
3 yrs NANANANANA
5 yrs
Death
1 yr
2.6‡ 4.7‡ 0.29
3 yrs
NANANANANA
5 yrs
MI
1 yr
9.2 10.9 0.61
3 yrs
NANANANANA
5 yrs
TLR
1 yr
23.5 15.6 0.06
3 yrs
NANANANANA
5 yrs
*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 =
polytetrafluoroethylene; 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.
BARRICADE RECOVERS SOS RRISC ISAR-CABG
39.2* 28.0* 0.07
60.2 37.0 0.001
68.3 51.8 0.007NA
7.0
18.8 11.2 0.13
NA
29.8
14.2 11.3 0.53
21.0 14.1 0.21
NA
26.2 17.4 0.16
28.2 21.1 0.46
37.4 21.8 0.02
43.9 29.6 0.04
NA
5.0
22.3
23.1† 15.9† 0.15 15.8† 29.7† 0.15
NANANANANA
0.51
2.6†NA2.8†NA0.92
NA NA NA
0.20
14.1† 5.5† 0.02
NANANANANA
9.6† 8.3† 0.84
NANANANANA
54 77 0.49
NA NA NA
NA
12 5 0.27 5.2 4.7 0.82
24 13 0.19
NA NA NA
NA
15 31 0.10
17 46 0.01
NA
5 28 0.003
10 41 0.004
NA
58 41 0.13
NA NA NA
2.6† 0† 0.99
29 0 <0.001
2.6† 0† 0.99
18 5 0.15
NA NA NANA NA NA
5.3† 21.6† 0.05
24 30 0.55
NA NA NANA NA NA
15.4 22.1 0.0337 49 0.20
NANANANANA
NA
NANANANANA
NANA NA NA
4.2 6.0 0.27
NANANANANA
NA
7.2 13.1 0.02
NANANANANA
NA
FIGURE 26.14 Major adverse cardiac events, death, myocardial infarction, and target-lesion revascularization complications as recorded in saphenous
vein graft stent studies. PES, paclitaxel-eluting stent; SES, sirolimus-eluting stent. From Lee MS, Park SJ, Kandzari DE, et al. Saphenous vein graft
intervention. J Am Coll Interv 2011;4:831e43 and Patel PM, Kern MJ. PCI in failing saphenous vein grafts: DES trumps BMS for the older patient. Cath
Cardiovasc Interv 2016;87:50e1 with permission.
The Spectrum of Clinical Presentations and Management Options Chapter | 26 391
https://t.me/med1917
Among DES patients (n ¼ 31,403), 3-year mortality was lower (vs. BMS) (22.7% vs. 28.0%, P < .001; HR 0.87, 95% CI
0.83e0.91), and no difference was observed in the adjusted risk for MI (HR 0.97, 95% CI 0.91e1.03) or urgent
revascularization (HR 1.04, 95% CI 0.99e1.08). These findings were independent of clinical presentation, previous lesion
treatment, and graft segment (P interaction, NS). The investigators concluded that in this large SVG PCI cohort the allcause mortality was lower among those receiving DES, and no difference in MI or urgent revascularization was
observed up to 3 years.
Consequently, several authorities opined that PCI to SVG using DES may be a superior treatment option, at least for the
elderly patients [71].
NOVEL STENTS FOR SAPHENOUS VEIN GRAFT PERCUTANEOUS CORONARY
INTERVENTION
Covered Stents
Considering the burden of thrombus in SVGs, conceptually, the use of covered stents in SVG intervention could be
beneficial. Th ese stents are des ign ed to entrap ath eros cl er ot ic plaque and its accom panying thrombotic material,
therefore potentially preventing distal microembolization [41]. However , thr ee pros pe ct ive rand om ized tr ia ls faile d to
demonstrate benefit with covered stents [60]. The SYMBIOT III (Self-Expanding PTFE Stent Graft During SVG
InterventiondLate Results), a prospective, randomized trial, compared the self-expandable polytetrafluoroethylene
(PTFE)-covered nitinol Symbiot stent (Boston Scientific Corp., Natick, MA, USA) with the BMS [72]. At 8 months, the
incidences of MACE in both groups were similar (30.6% vs. 26.6%, P ¼ .43). A trend toward increased target-lesion
revascularization and reduction of post-PCI creat ini ne kinase (CK) release was observed with the Sym biot stent
(23.5% vs. 15.6%, P ¼ .055). This was associated with a poor long-term outcome with higher rates of restenosis and
need for TVR and target-lesion revascularization compared with BMS. The RECOVERS (Randomized Evaluation of
Polytetrafluoroethylene-Covered Stent in Saphenous Vein Grafts) trial [73] randomized 301 pat ients to the PTFEcovered, balloon-expandable JOSstent (Jomed International AB, Helsingborg, Sweden) or BMS. The covered stent
group had a higher incidence of 30-day MACE (10.9% vs. 4.1%, P ¼ .047), mainly attributed to increased incidence of
MI (10.3% vs. 3.4%, P ¼ .037). At 6-month follow-up the restenosis and MACE rates were not different between the
two groups: 24.2% versus 24.8%, P ¼ .237, and 23.1% versus 15.9%, P ¼ .153, respectively. Another study, the
BARRICADE (Barrier Approach to Restenosis: Restrict Intima to Curtail Adverse Events) trial [74] randomized 243
patients to the same treatment arms, reporting that at 5-year follow-up the target vessel failure was higher in the covered
stent group than in the BMS group (68.3% vs. 51.8%, P ¼ .007).
The MGuard (InspireMD, Tel Aviv, Israel) stent offers a unique thrombus-capturing platform [75,76]. The group most
experienced with utilization of this stent has published their results from 163 consecutive patients who underwent the
MGuard implantation, including 109 patients who underwent SVG PCI. The mortality in the SVG group was 10% versus
1.9% for PCI in native coronary arteries; stent thrombosis occurred in 2% of both groups and MACE rates at 1-year followup were 29% in the SVG group and 11% in the native arteries group. The difference in MACE rate was mainly due to
target-lesion/target-vessel revascularization [77]. The investigators concluded that for select patients undergoing SVG PCI
the MGuard provides a suitable therapeutic strategy and recommended further evaluation to define potential merits and
limitations.
Another novel device, the SESAME stent (Advanced Bioprosthetic Surfaces, San Antonio, TX, USA) consists of a
membrane-covered, self-expanding, superelastic metal endoprosthesis platform. In the early utilization SESAME trial 20
patients underwent SVG intervention, resulting in a 0% MACE rate at 30 days that increased to 14% at 9 months [78].
Based on the aforementioned studies the overall impression is that at this stage the PTFE stents do not yet appear to
significantly reduce the long-term MACE rates.
Pericardium-Covered Stent
This unique percutaneous implantable device consists of a cylindrical equine pericardium that covers a stainless steel stent,
which is premounted on a delivery catheter and stored in a specially designed package to provide the device with a 2-year
shelf life. The two pericardium-covered stent (PCS) CE-certified brands available are the Over and Under and the
AneuGraft (ITGI Medical, Or Akiva, Israel), which is specially designed for application in tortuous vessels. The experience with PCSs in SVGs is so far limited to two small registries with short follow-up. The SLEEVE I, an open-label,
nonrandomized, feasibility study of 15 patients with 22 lesions, recorded a procedural success rate of 100% (defined
392 Cardiovascular Thrombus
https://t.me/med1917
45
40
35
30
25
TLR (%)
20
15
p=0.83
10
9.6
5
0
RECOVERS trials
6 months
Covered stents
p=0.17
13
8.3
StentsIVGrafts
6 months
BMS
6.9
p=0.06
18.4
11. 5
Symbiot II Trial
8 months
p=0.66
15.6
13.5
BARRICADE
Trial 9 months
p=0.04
43.9
29.6
BARRICADE
Trial 5 years
p=0.89
27
25
STROMBOLI*
Trial 5-7 years
Covered stents BMS
70
60
50
40
MACE (%)
30
p=0.15
20
23.1
0
RECOVERS trials
6 months
15.9
10
p=0.78
21
20
StentsIVGrafts
6 months
p=0.43
30.6
26.6
Symbiot II Trial
8 months
p=0.08
32.2
22.1
BARRICADE Trial
9 months
p=0.007
68.3
51.8
BARRICADE Trial
5 years
FIGURE 26.15 Sample of randomized trials comparing the use of covered stents with bare metal stents (BMS) in percutaneous coronary intervention for
saphenous vein graft lesions. TLR, target-lesion revascularization. From Kilic ID, Fabris E, Serdoz R, et al. Coronary covered stents. EuroIntervention
2016;12:1288e95 with permission.
by <50% residual diameter stenosis), clinical success rate of 93%, and no in-hospital MACEs [79]. The SLEEVE II, a
multicenter, international registry of 47 patients, reported a 30-day cumulative MACE incidence of 10.6%. The technical
success (defined by the ability to reach the target SVG lesion, accurate stent positioning, and successful deployment) was
86% [80]. Notably, no acute or subacute stent thrombosis occurred. Fig. 26.15 displays data on several randomized trials
comparing the use of covered stents with BMS in PCI for SVG lesions.
ADJUNCTIVE PHARMACOTHERAPY FOR MANAGEMENT OF SAPHENOUS VEIN GRAFT
DISEASE
Vasodilators
Salloum and coinvestigators studied the release of vasoconstrictor molecules during SVG PCI. Laboratory measurements
in blood selectively aspirated from the graft before and after PCI showed a significant, 10-fold increase in serotonin level as
well as a strong release of endothelin in conjun ction with the PCI. In an observational study of 83 consecutive SVG PCI
procedures, the use of nicardipine (dihydropiridine calcium-channel blocker) immediately before direct stenting demonstrated an acceptable rate of 2.4% for no reflow and a global, in-hospital MACE rate of 3.8% [81]. These data support the
concept of a potential role of vasodilator agents (i.e., calcium-channel blockers, adenosine, and nitroprusside) in the
treatment and prevention of the dreaded no-reflow phenomenon [41,81].
Aspirin
All aspirin-containing regimens that were studied post-CABG showed improved graft patency compared with placebo
(P < .005). In addition, the use of aspirin has been shown to reduce in-hospital mortality without an associated increase in
hemorrhage-related risks. Consequently, administration of aspirin before and after CABG surgery is recommended by the
European and American guidelines [82,83].
Clopidogrel
Clopidogrel has been the mainstay of the dual antiplatelet therapy (DAPT) strategy for over 10 years, with corresponding
benefits in stenting for ACS being well established [8].Asforthebenefits of DAPT in SVG PCI, Gao and colleagues
reported a prospective, nonrandomized cohort of 102 post-CABGS patients assigned to clopidogrel 75 mg monotherapy
daily and 95 patients who received clopidogrel 75 mg plus aspirin 100 mg daily. No significant difference in SVG
patency as assessed by computed tomographic (CT) angiography was seen at 1 month or 1 year (for 1 month, 98.1% vs.
98.2%, P ¼ .73; for 1 year, 93.5% vs. 96.3%, P ¼ .25, respec tive ly ) [84]. Sun and colleagues compared postoperative
administration of DAPT with clopidogrel 75 mg plus aspirin 81 mg daily versus m on othe rap y with aspirin 81 mg in 100
patients who underwent standard on-pump CABG. U tilizi ng CT angiography for follow-up in 79 patients at 1 mont h, no
difference in SVG patency was found in both of the common types of bypass grafts (i.e., SVG and left internal mammary
artery [LIMA]) (92.9% vs. 95% , respectively, P ¼ .43) or in SVG alone (93.2% vs. 93.5%, respectively, P ¼ .92) [85].
The Spectrum of Clinical Presentations and Management Options Chapter | 26 393
https://t.me/med1917
Gao and colleagues randomized 249 patients to either clopidogrel 75 mg plus aspirin 100 mg daily or monotherapy w ith
aspirin 100 mg administered within 48 h of surgery [86]. CT angiography for assessment of the SVG patency at 3-month
follow-up was obtained in 90% of patients; however, blinding of treatment or placebo control was not done. The patency
rate was higher in the DAPT group compared with the aspirin monotherapy group (85.7% vs. 91.6%, P ¼ .04). Then
the randomized, double-blind, placebo-controlled CASCADE study (Clopidogrel After Surgery for Coronary Artery
Disease) [87] compared aspirin 162 mg monotherapy with DAPT (aspirin 162 mg plus clopidogrel 75 mg) in 113 patients, demonstrating an overall graft patency (95.2% vs. 9 5.5%, DAPT vs. aspirin alone; P ¼ .90) and SVG patency
(94.3% vs. 93.2%, respectively, P ¼ .69) that were not s igni ficantly different between the treated groups. Rafiqand
colleagues conducted a randomized trial comparing DAPT with aspirin monotherapy in hypercoagulable patients who
underwent CABG. Accordingly, no difference in SVG patency rates at 3 months was identified [88]. An important
prospective, multicenter study, the ADAPT-DES (Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents),
stratified patients according to whether they underwent PCI of an SVG lesion (405 patients) or a non-SVG lesion [37]
and 2-year outcomes were compared between these groups. The main purpose of this study was studying the high
platelet reactivity (HPR) in SVG PCI with second-generation DES versus PCI in native coronary vessels. The results
indicated that SVG PCI was independently associated with ahigher2-yearriskofMACEs(adjustedHR2.34;95%CI
1.69e3.23; P < .0001), ischemia-driven TVR (adjusted HR 1.82; 95% CI 1.37e2.42; P < .0001), and stent thrombosis
(adjusted HR 2.26; 95% CI 1.42e3.59; P ¼ .0006), but not of bleeding (adjusted HR 0.99; 95% CI 0.68e1.46; P ¼ .97).
There was no statistical interaction between HPR and SVG PCI in regard to MACEs (adjusted P interaction ¼ .99). The
investigators concluded that SVG PCI is associated with a considerably higher risk of 2-year adverse ischemic events,
with HPR conferring similar risk in SVG and non-SVG PCI. They propos ed tha t more potent and longer antiplatelet
therapy may be beneficial for patients undergoing SVG PCI.
At this writing, the guidelines recommend 1 year of DAPT post-CABG in patients presenting with ACS or for those
who undergo off-pump coronary artery bypass surgery. The DAPT includes clopidogrel, prasugrel, or ticagrelo r (preferred
over clopidogrel) [89]. However, in light of the aforementioned investigations, the guidelines will probably be updated to
include treatment with more potent and longer antiplatelet therapy to benefit patients undergoing SVG PCI.
Ticagrelor/Prasugrel
The evidence supporting newer, more potent antiplatelet agents for stent management than the standard clopidogrelbased DAPT was generated by two ma jor studies, PLATO [90] and TRITON-TIMI 38 [91,92].Thefindings of these
studies carry implications for the management options of patients with SVG degenerative disease who require revascularization. The PLATO study, a large randomized trial that compare d DAPT with ticagrelor versus DAPT with
clopidogrel concluded that in ACS PCI ticagrelor significantly improved clinical outcomes without an increase in the
rate of overall major bleeding [90]. Among the study’s 1584 patients (12%) who underwent CABG, a related fatal
bleeding uncommonly occurred, limited to 6 patients in each treatment group (0.8% and 0.7% of patients receiving
ticagrelor vs. clopidogrel, respectively). Further subgroup analysis identified the use of ticagrelor to be associated with
better clinical outcomes compared with clopidogrel in ACS p atie nts with prior CABG and in those who underwent redo
CABG. In t he TRITON-TIMI 38 study ACS patients who underwent CABG had short-term significant reduction of allcause mortality with prasugrel-based DAPT compared with clopidogrel DAPT (2.31% vs. 8.67%, adjusted odds ratio
[OR] 0.26; P ¼ .025); however, there was an increase in observed bleeding, platelet tr an sf usio n, and need for surgic al
reexploration for bleeding management in patients randomized to receive prasugrel [91]. A 2016 retrospective observational study compared treatment with ticagrelor-based DAPT (n ¼ 1266) with clopidogrel-based DAPT (n ¼ 978) in
ACS patients who underwent CABG [92]. The overall risk of major CABG-related bleeding complications was lower
with ticagrelor than with clopidogrel (12.9 vs. 17.6%, adjusted OR 0.72, 95% CI 0.56e0.92; P ¼ .012). The incidence of
CABG-related major bleeding was higher when ticagrelor and clopidogrel were discontinued less than 24 h be for e
surgery. Discontinuation of these medications 3 days before surgery did not increase the incidence of major bleeding
complications with ticagrelor; however, it was increased with clopidogrel.
Glycoprotein IIb/IIIa Inhibitors
Recognizing the roles of thrombus and platelet activation and abnormal aggregation in the pathogenesis of ACS, treatment
with glycoprotein (GP) IIb/IIIa receptor inhibitors became an established therapy in reducing short- and intermediate-term
outcomes of patients undergoing PCI of native coronary arteries and SVGs alike [93,94].
394 Cardiovascular Thrombus
https://t.me/med1917
In a pooled analysis of randomized trials of GP IIb/IIIa receptor inhibitor agents, Roffi and associates [95] analyzed
389 patients treated with GP IIb/IIIa inhibitors: 51% abciximab, 49% eptifibatide, and 216 who were m anag ed with
placebo. The incidence of death, MI, or urgent revascularization at 30 days was 16.5% in the GP IIb/IIIa re cep tor
inhibitor group versus 12.6% among the pl aceb o group (OR 1.38; 95% CI 0.85e224, P ¼ .18). At 6-month follow-up,
the event rates were 39.4% and 32.7% for th e GP IIb/IIIa receptor inhibitors versus the placebo, respectivel y (HR 1.29,
95% CI 0.97e1.72, P ¼ .07). Importantly, the incidence of major bleeding was almost fivefold higher among those
randomized to platelet GP IIb/IIIa inhibitors compared with placebo (6.8% vs. 1.4%, P ¼ .0004) [93,95,96].TheEPIC
trial showed no decrease in the rate of distal embolizat ion and a trend toward lower incidence of early large non-Q-wave
MI among patients tre at ed with GP IIb/IIIa recepto r inhibitors, and the 30-d ay and 6-month clinical end points were
similar in both groups [92,97]. The FIRE trial demonstrated that GP IIb/IIIa inhibitors, when used in conjunction with
the FilterWire EPD, had better outcomes, better flow through the filter, reduced procedural ischemia, and less abrupt
closure, no reflow, or distal emboli zation [9 3, 98]. The TARGET (Thrombolytic Activity Reassessment and Genotyping)
study investigato rs [99] demonstrated that in the current strategy of combined stenting and administration of GP IIb/IIIa
receptor antagonist, thrombus is still the angiographic characteristic most closely associated with adverse outcome of
PCI in SVGs.
Accordingly, pertinent questions have been raised as to the routine practice of administration of GP IIb/IIIa
receptor antagonists in PCI of bypass venous grafts [100]. Altogether, based on the data and the lack of prospective
randomized studies it appears that the use of GP IIb/IIIa inhibitors does not offer any significant benefit in the setting of
PCIofSVGs.
Anticoagulants
Most trials assessing the use of anticoagulants to prevent SVG failure are old and enrolled a small number of patients while
directly comparing anticoagulants with antiplatelet therapy [8]. Gohlke et al. randomized 89 patients to a vitamin K
antagonist (beginning on the seventh postoperative day) and 84 patients to no anticoagulation. Graft patency after surgery
was 90.4% in the treatment group and 84.6% in the control group (P ¼ .015) [101]. The Post Coronary Artery Bypass
Graft trial assigned 1351 CABG patients to aggressive or moderate treatment to lower low-density lipoprotein cholesterol
levels and to treatment with warfarin or placebo [102]. Angiographic follow-up at 4 years showed no improvement in
graft patency comparing the warfarin and the placebo groups. Interestingly, aggressive lowering of cholesterol did reduce
the progression of atherosclerosis, thus potentially decreasing the risk of subsequent SVG thrombosis. Other trials did
not show any clinical advantage of warfarin over antiplatelet therapy as well. Consequently, the use of anticoagulants postCABG is not supported in the guidelines [8,103].
Saphenous Vein Graft Treatment With Novel Oral Anticoagulants Versus Percutaneous
Coronary Intervention
PCI has traditionally been the treatment of choice for ACS patients presenting with abrupt SVG thrombotic occlusion. A
different strategy involving NOAC (novel oral anticoagulant) treatment for SVG thrombosis has been entertained, with an
interest in obviating the need for PCI [104]. Practically, this option implies that NOACs might be assigned as a “destination
therapy” for SVG thrombosis in the setting of ACS. It appears that this approach may be suitable, safe, and effective in
select patients with focal, non-flow-limiting thrombotic SVG occlusion, absent significant angiographic graft disease.
However, it is unclear as to which thrombus burden will be ideal for this therapy and whether thrombus dissolution with
NOAC treatment of SVGs occurs “spontaneously” over time or as a direct result of the NOAC treatment.
SUMMARY
The long-term efficacy of coronary artery bypass surgery remains limited because of VGF and progression of atherosclerosis in native coronary arteries. Thrombosis plays a major role in these processes. Atherosclerotic plaques in SVGs are
more diffuse and friable, frequently containing layers of old thrombi interspersed with plaques or superimposed on layers
of old thrombus. The friability of the SVG plaques and, especially, the presence of accompanying thrombus increase
susceptibility to PCI-induced distal embolization, no-reflow phenomenon, and distal microvascular obstruction. This accounts for the majority of acute angiographic and clinical complications. The management of SVGs containing significant
thrombus burden is challenging, and application of dedicated mechanical thrombus removal technology may be required to
ensure successful stent delivery and deployment. Overall, the current thera py of SVG thrombotic atherosclerotic disease
Соседние файлы в папке Библиотека им академика М.И. Перельмана