Добавил:

Sekretar kiopkiopkiop18@yandex.ru t.me/Prokururor I Вовсе не секретарь, но почту проверяю Опубликованный материал нарушает ваши авторские права? Сообщите нам.

Вуз:

Ростовский Государственный Медицинский Университет

Предмет:

Медицина общая

Файл:

Книга_3614_Библиотеки_им_академика_М_И_Перельмана

.pdf

Скачиваний:

Добавлен:

30.08.2026

Размер:

73 Мб

Скачать

☆

<<< < Предыдущая 1 2 3 4 5 6 7 8 9 1011 / 5011 12 13 14 15 16 17 18 19 20 21 22 23 24 25 > Следующая >>>

https://t.me/medicina_free

Evidence basis fordecision- making betweencoronary artery bypass graing and percutaneous coronaryintervention

Present and future perspectives

Vasim Farooq, John D. Puskas, Patrick W. Serruys, and David P. Taggart

‘Choosing to make selective choices among competing evidence, so as to emphasize those results that support a given position, while ignoring or dismissing any ndings that do not support it, is a practice known as “cherry picking” and is a hallmark of poor science or pseudo- science.’

Richard Somerville, American Climate Scientist, Testimony before the US House of Representatives

Committee on Energy and Commerce Subcommittee on Energy and Power, 8 March 2011.

Introduction

Historically, the 15 randomized clinical trials comparing coronary artery bypass gra (CABG) surgery and percutaneous coronary intervention (PCI) for intervention in coronary artery disease (CAD) have been criticized for profound selection bias (‘cherrypicking’ of patients).–  e stringent clinical and angiographicbased inclusion criteria led to only 2– 12% of all screened patients actually being randomized in these trials, resulting in recruitment of mainly low risk subjects with predominant one- or two- vessel disease (and a low incidence of three- vessel disease (3VD)), preserved le ventricular ejection fraction (LVEF), and a low incidence of diabetes., is highly selective selection practice echoes that of a review of 31 antidepressant ecacy trials in 2002, demonstrating that despite the large number of trials and participants, only a minority of patients treated for depression in routine clinical were eligible for inclusion because of a large number of exclusion criteria.,

Consequently, applying these trial ndings (or meta- analyses, particularly those that mix historical with contemporary data– ) to real- world contemporary clinical practice eectively generalizes therapeutic choices to the larger population who were eectively excluded from the trials. erefore, this risks erroneous assignment of many patients to therapies that are actually suboptimal. Aparticularly pertinent example is a meta- analysis of the historical trials of CABG versus PCI that reported CABG to have a mortality benet in older rather than younger subjects; ndings that

were subsequently directly contradicted by the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) trial where the opposite was shown.,

SYNTAX, FREEDOM, andBEST

e SYNTAX trial was designed to overcome the historical limitations of prior trial data comparing CABG with PCI, by incorporating an ‘all- comers’ design if the Heart Team determined ‘equivalent anatomical revascularization’ could be achieved between CABG and PCI (using the rst- generation drug- eluting stent (DES)), with accompanying parallel nested CABG and PCI registries for patients deemed ineligible for randomization.–  Overall, the 5- year outcomes of SYNTAX reported that major adverse cardiac and cerebrovascular events (MACCE) occurred in 26.9% of CABG and 37.3% of PCI patients (P <0.0001). Myocardial infarction (3.8% in CABG vs 9.7% in PCI; P <0.0001) and repeat revascularization (13.7% in CABG vs 25.9% in PCI; P <0.0001) were signicantly increased with PCI compared to CABG. However, all- cause mortality and stroke did not dier signicantly between CABG and PCI (11.4% in CABG vs 13.9% in PCI, P=0.10; and 3.7% vs 2.4%, P=0.09, respectively).

e relative benets of CABG and PCI varied according to the anatomical SYNTAX score tertiles (low 0– 22, intermediate 23– 32, high ≥33) that indicated the severity of CAD. Overall, MACCE occurred in 28.6% of CABG and 32.1% of PCI patients with a low (<23)

SECTION 2 Treatment ofcoronary artery disease

No. at risk

All-cause mortality(a) (b)

Myocardial infarction

No. at risk

Cumulative event rate (%)

No. at risk

https://t.me/medicina_free

SYNTAX score (P=0.43). With le main coronary disease MACCE occurred in 31.0% of CABG and 36.9% of PCI patients (P=0.12). Overall, in patients with intermediate (23– 32) or high (>32) anatomical SYNTAX scores, MACCE was signicantly increased with PCI (intermediate score:25.8% CABG vs. 36.0% PCI, P =0.008; high score:26.8% CABG vs 44.0% PCI, P <0.0001) (Fig. 9.1).

P = 0.10

48 60 0122436

761 803

903

CABG (n = 897) PCI (n = 903)

12 24 36

820 859

Months since allocation

810 853

788 832

Cumulative event rate (%)

CABG 897

Ten- year follow- up of SYNTAX demonstrated 248/ 903 (28%) patients had died aer PCI and 212/ 897 (24%) aer CABG (hazard ratio (HR) 1.19 [95% CI 0.99– 1.43], p=0·066). Vital status information at 10years was complete for 841 (93%) patients in the PCI group and 848 (95%) patients in the CABG group. As in the 5- year analysis, a signicant survival benet of CABG over PCI emerged in patients

P < 0.0001

13.9%

9.7%

11.4%

606 537

897 903

Months since allocation

800 832 821

784 759

792

48 60

730 756

3.8%

575 593PCI

Stroke

Cumulative event rate (%)

CABG 897

903

(e) (f)

Repeat revascularization

12 24 36

806 854

Months since allocation

790 842

763 815

P = 0.09

3.7%

2.4%

48 60 0122436

732 782

579 622

P < 0.0001 P < 0.0001

25.9%

13.7%

Death or stroke or myocardial infarction

Months since allocation

897 903

MACCE

787 830 824

776 749

792

P = 0.03

20.8%

16.7%

48 60

717 756

37.3%

26.9%

566 592PCI

CABG 897

903

12 24 36

778 760

Fig.9.1 Five- year results of the SYNTAX trial.

Reproduced from Mohr FW, Morice MC, Kappetein AP, etal. Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three- vessel disease and left main coronary disease:5- year follow- up of the randomised, clinical SYNTAX trial. Lancet. 2013 Feb 23;381(9867):629– 38. doi:10.1016/ S0140- 6736(13)60141- 5 with permission from Elsevier.

Months since allocation

760 740

717 688

48 60 0122436

677 644

532 495

897 903

751 741 733

Months since allocation

739 694

681

48 60

654 634

512 483PCI

9 Evidence basis fordecision-making betweencoronary artery bypass grafting and percutaneous coronaryintervention 81

Primary outcome

Death, myocardial infarction,

Death from any cause (%)

No. at risk

PCI CABG

947

814

758

613

422

221

CABG

947

855

806

655

449

243 238

012345

100

No. of patients at risk

PCI CABG

465

427

409

391

373

342

303

252

206 191

https://t.me/medicina_free

Fig.9.2 Five- year results of the FREEDOM trial.

Source data from Farkouh ME, Domanski M, Sleeper LA, etal; FREEDOM Trial Investigators. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med. 2012 Dec 20;367(25):2375– 84. doi:10.1056/ NEJMoa1211585.

with 3VD at 10year (28% vs 21%; HR 1.42, 95% CI 1.11– 1.81) but not in patients with le main CAD (27% vs 28%; HR 0.92, 95% CI

0.69– 1.22), p interaction=0·023.

the cardiac surgeon and the interventional cardiologist agreed could be oered equivalent anatomical revascularisation, and similarly equally be oered CABG or PCI on the grounds of clinical comorbidity, were eligible for randomisation. As a result patients were nested in CABG (n- 1077, predominantly for patients where equivalent anatomical revascularisation between CABG and PCI could not be achieved) and PCI (n=198, predominantly for patients where the clinical co- morbidity made surgical revascularisation prohibitive) registries. With advances in surgical and percutaneous revascularisation techniques since SYNTAX, it may be argued that more patients would have been deemed by the heart team to be suitable for equivalent anatomical revascularisation and hence eligible for randomisation. As a result fewer patients may have been enrolled in the nested registries. As to whether this would have impacted the outcomes of the original SYNTAX Trial is debatable.

with Diabetes Mellitus:Optimal Management of Multivessel Disease (FREEDOM) trial,, which investigated diabetic patients with multivessel disease, and the Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus- Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease (BEST) trial, which utilized second- generation DES in multivessel disease (rather than the rst- generation DES used in SYNTAX), have largely mirrored the ndings of SYNTAX, conrming that in complex CAD surgical revascularization should be considered the primary revascularization strategy. In FREEDOM, at 5years, the primary composite endpoint of all- cause mortality, nonfatal myocardial infarction, or non- fatal stroke, occurred in 26.6% of PCI and 18.7% of CABG patients (P=0.005). e benet of CABG was due to dierences in rates of both myocardial infarction (13.9% in PCI vs 6.0% in CABG patients; P <0.001) and all- cause mortality (16.3% in PCI vs 10.9% in CABG patients; P=0.049). Stroke was

P = 0.005 by log-rank test 5-yr event rate: 26.6% vs 18.7%

925

PCI

416

CABG

219

or stroke (%)

953

848

2345

Years since randomization Years since randomization

788

Although SYNTAX was an ‘all- comers’ trial, only patients that

Subsequently, the Future Revascularization Evaluation in Patients

Death

P = 0.049 by log-rank test

5-yr event rate: 16.3% vs 10.9%

No. at risk

PCI

953

897

845

685

PCI

CABG

466

more frequent in CABG patients, with 5- year rates of 2.4% in the PCI group and 5.2% in the CABG group (P=0.03) (Fig. 9.2). At 7- years extended follow- up of FREEDOM (for 943 out of 1800 patients), all- cause mortality occurred in 23.7% of PCI and 18.7% of CABG patients (HR 1.32, 95% CI 0.97– 1.78; P=0.07) (Fig. 9.3).

e BEST trial demonstrated occurrence of the primary endpoint (composite of death due to myocardial infarction or target- vessel revascularization at 2years) in 11.0% of PCI patients and 7.9% of CABG patients (P=0.32 for non- inferiority). At longer- term followup (median, 4.6years), the primary endpoint occurred in 15.3% of PCI and 10.6% of CABG patients (HR 1.47, 95% CI 1.01– 2.13; P=0.04) (Fig. 9.4).

Unadjusted HR (95% Cl): 1.32 (0.97 to 1.78)

Probability of survival

478

P = 0.07 by log-rank test

2 345678

Time From randomization to death, years

PCI CABG

449

429

405

384

358

326

260

Fig.9.3 Seven- year results of the FREEDOM trial.

Reproduced from Farkouh ME, Domanski M, Dangas GD, etal; FREEDOM Follow- On Study Investigators. Long- Term Survival Following Multivessel Revascularization in Patients With Diabetes:The FREEDOM Follow- On Study. J Am Coll Cardiol. 2019 Feb 19;73(6):629– 38. doi:10.1016/ j.jacc.2018.11.001. with permission from Elsevier.

SECTION 2 Treatment ofcoronary artery disease

Primary composite endpoint

012345

PCI CABG

442

415

377

326

262

126 145

Number at risk

https://t.me/medicina_free

Cumulative incidence (%)

Fig.9.4 Results of the BEST trial.

Source data from Park SJ, Ahn JM, Kim YH, etal TK; BEST Trial Investigators. Trial of everolimus- eluting stents or bypass surgery for coronary disease. N Engl J Med. 2015 Mar 26;372(13):1204– 12. doi:10.1056/ NEJMoa1415447.

Anatomical complexity (SYNTAX score), clinical factors, and their impact ondecision- making

Anatomical complexity (SYNTAX score)

Based on the results of SYNTAX, the anatomical SYNTAX Score (http:// www.syntaxscore.com) has now emerged as a clinical tool to objectively determine the complexity of CAD, and guide decisionmaking between CABG surgery and PCI. e anatomical SYNTAX score allows a more objective assessment of the angiographic extent of CAD, compared to simple ‘eye- balling’, that continues to dominate contemporary clinical practice., e anatomical SYNTAX score (Fig.9.5a, b) combines a number of factors including the anatomical location of all coronary lesions in vessels 1.5mm in diameter or greater, their importance in supplying blood to the myocardium (‘vessel- segment weighting’ based on the Leaman score), the severity of the diseased coronary artery segment (i.e. obstructive or occlusive), adverse characteristics for revascularization (based on the American College of Cardiology/ American Heart Association lesion classication),, the Medina classication system for bifurcation lesions, and total occlusion characteristics from the European TOTAL Surveillance Study.

e potential value of the anatomical SYNTAX score in decisionmaking between CABG and PCI in complex CAD was rst recognized in the 5- year follow- up of the Arterial Revascularization erapies Study (ARTS) II, that demonstrated a signicant separation of clinical outcomes in patients stratied according to anatomical complexity of CAD (tertiles of the anatomical SYNTAX score).

Following ARTS II, the anatomical SYNTAX score was adopted in the SYNTAX trial, where it was used as a tool to force the cardiac surgeons and interventional cardiologists to systematically analyse the coronary angiogram and to specify the number of

100

438

P = 0.04 by log-rank test

Years since randomization

402

362

345

305

242

PCI

CABG

17.0%

11.7%

coronary lesions requiring treatment, their angiographic location, anatomical complexity, and to specify which coronary lesions required revascularization (based on a vessel size of ≥1.5mm), before agreeing that equivalent anatomical revascularization could be achieved— only then was the patient considered to be suitable for randomisation in SYNTAX, provided the surgical risk was not prohibitive.

Based on tertiles of the anatomical SYNTAX score (low 0– 22, intermediate 23– 32, high ≥33) (Fig. 9.5c), it was demonstrated that the more complex the coronary anatomy, the greater the potential longer- term prognostic benet of CABG compared to PCI.  ese ndings have since been validated in multiple registries worldwide.

However, both FREEDOM, and BEST failed to show any interaction for the SYNTAX tertiles (low 0– 22, intermediate 23– 32, high ≥33) with clinical outcomes. e two most likely reasons were the exclusion of patients with more complex CAD that meant these studies were eectively underpowered to examine the eects of the anatomical SYNTAX score, compounded by the relatively short follow- up of both studies (minimum follow- up 2 years in FREEDOM and BEST compared to 5years in SYNTAX) and the subsequent early termination of BEST due to slow recruitment.,

Ongoing studies are currently using the anatomical SYNTAX score (and SYNTAX score II (that incorporates clinical factors)) in unprotected le main CAD–  and de novo 3VD.

Clinicalfactors

As was shown with anatomical complexity of CAD in the SYNTAX trial, the same scenario exists with clinical comorbidity such as diabetes that equates to a potentially greater prognostic benet for CABG compared to PCI in complex disease, provided the risks of surgical revascularization are not prohibitive.,

Traditionally, it has been argued that provided stents can treat all obstructive coronary lesions, then outcomes between CABG and PCI would be similar, and that improvements in stent technology would mean that eventually PCI should surpass CABG., However, focusing on stent technology rather than the atherosclerotic disease process misunderstands the benets of bypass surgery (as explained subsequently).

Clinical consequences ofexcess plaque burden and/ or clinicalcomorbidity

Based on the results of SYNTAX, FREEDOM, and BEST, it may be surmised that clinical outcomes in complex CAD are primarily due to excess plaque burden and progression, and/ or clinical comorbidity, with the consequent risk of developing future vulnerable plaque(s) and myocardial infarction., A substudy of the COURAGE, trial demonstrated that the overall coronary atherosclerotic disease burden was a more consistent predictor of myocardial infarction and cardiac death compared to myocardial ischaemia alone. Furthermore, in a registry of patients with suspected CAD who underwent computed tomography (CT), quantication of atherosclerotic burden (lesion localization, degree of stenosis, and plaque composition) demonstrated that patients with non- obstructive CAD with a high plaque burden had at least a similar long- term prognosis (death or myocardial infarction) to patients with known obstructive CAD.

Greater anatomical complexity of CAD and/ or clinical comorbidity such as diabetes, chronic kidney disease, or impaired LVEF

–

9 Evidence basis fordecision-making betweencoronary artery bypass grafting and percutaneous coronaryintervention 83

(a)

https://t.me/medicina_free

Right dominance

16a

Left dominance

16b

16c

(c)

12a

12b

14a

14b

12a

12b

14a

14b

10a

Weighting

Factor

+3.5

+2.5

+1.5

+0.5

(b)

Diffuse

Small

Thrombus

Dominance

Heavy

Calciﬁcation

Diseased

Segment #

SYNTAX

Score

Length

Total

Occiusion

Severe

Tortuosity

Trifurcation

Bifurcation

Aorta Ostial

% of patients

0612 18 24 30 36

42 48 54 60 66 72 78 84

SYNTAX score

CABG RCT PCI RCTCABG Registry PCI Registry

Fig.9.5 The anatomical SYNTAX score. (a)Coronary tree segments and their importance in supplying blood ﬂow to the left ventricle (vessel segment

weighting- factors— Leaman score

53,54

) based on the presence of a right or left dominant system.28 Amultiplication factor of ×2 is used for non- occlusive

lesions (50– 99% diameter stenosis) and ×5 for occlusive (100% diameter stenosis) lesions. For example, a stenotic proximal LAD lesion (segment

6)would have a weighting factor of 3.5×2 (7 points), and an occlusive proximal LAD lesion a weighting factor of 3.5×5 (17.5 points). (b)Other adverse lesion characteristics considered in the SYNTAX score have an additive value. (c)Within the SYNTAX trial,16 the distribution of the anatomical SYNTAX was found to be Gaussian in the randomized PCI and CABG populations with the curves almost being superimposable on each other. When the scores of the randomized SYNTAX population were divided into tertiles, the upper boundary of the lowest tertile was 22 (low risk), the second tertile ranged from 23 to 32 (intermediate risk), and the lower boundary for the highest tertile is equal or greater than 33 (high risk). Based on these tertiles, current European revascularization guidelines76 give patients with 3VD and low SYNTAX scores (0– 22) a level of evidence of IA (evidence and/ or general agreement that a given treatment or procedure is beneﬁcial, useful, effective— is recommended/ is indicated) for CABG. For 3VD without diabetes, the same level of recommendation (IA) as CABG is given for PCI, whereas for 3VD with diabetes the recommendation is reduced for PCI, with a level of evidence of IIb A(usefulness/ efﬁcacy is less well established by evidence/ opinion— may be considered). With 3VD with intermediate– high SYNTAX scores (>22), this remains within the realms of CABG, with a level of evidence IA compared to IIIA (evidence or general agreement that the given treatment or procedure is not useful/ effective, and in some cases may be harmful— is not recommended) for PCI irrespective of diabetic status. In patients with ULMCA disease and low SYNTAX score (<23), a level of evidence of IA is given for CABG and PCI, for an intermediate SYNTAX score (23–

32) a level of evidence for CABG as IA and PCI IIa A(weight of evidence/ opinion is in favour of usefulness/ efﬁcacy— should be considered). In patients with high SYNTAX scores (>32) this remains within the realms of CABG (level of evidence IA compared to IIIB for PCI).

Images adapted and used with permission from the SYNTAX Trial Investigators.

implies an increased likelihood of the patient having a greater plaque burden and the presence (or future development) of vulnerable plaque, particularly in the proximal vessels. In addition, with existing impaired LVEF, the clinical consequences of an acute myocardial infarction are more profound, with a greater risk of cardiogenic shock and mortality.

Differing therapeutic mechanisms ofCABG andPCI

Although excess clinical comorbidity is known to increase the short- term surgical operative risk, this is counter- balanced by a potentially greater longer- term prognostic benet of CABG. ere are three fundamental dierences between CABG and PCI. First,

SECTION 2 Treatment ofcoronary artery disease

https://t.me/medicina_free

bypass gras to the mid coronary vessel confer a longer- term protective eect by preventing the clinical consequences of proximal plaque progression or rupture compared to a stent— irrespective of generation— which simply treats the obstructive lesion alone but oers no protection against disease progression.,,,, Second, the longer- term durability of arterial gras, which elute vasoprotective agents into the coronary circulation and are accompanied by lower shear stress in the bypassed native coronary artery, compared to saphenous vein gras, may be important.–  ird, PCI in contrast to CABG may increase the likelihood of more incomplete revascularization if patients are not appropriately selected. More incomplete revascularization is a key factor in determining future MACCE and mortality.,

SYNTAX scoreII

e SYNTAX score II, is the anatomical SYNTAX score augmented by clinical variables that have been shown to alter the threshold value of the anatomical SYNTAX s core in complex CAD to allow comparison between CABG and PCI for long- term mortality (Fig. 9.6 and Fig. 9.7). Notably, reduced LVEF, impaired kidney function, younger age, and female sex were shown to substantially lower the anatomical SYNTAX scores to allow for equipoise for long- term mortality between CABG and PCI (Fig. 9.8). Conversely, older age, unprotected le main coronary artery (ULMCA) disease, and the presence of chronic obstructive pulmonary disease (COPD) were shown to markedly raise the anatomical SYNTAX scores to allow for equipoise for long- term mortality between CABG and PCI.

e ndings of the SYNTAX score II do suggest that excess plaque burden and clinical comorbidity lie at the heart of decision- making between CABG and PCI, since either increases the likelihood of the presence, or future development, of vulnerable plaque, which would potentially be obviated with a bypass gra. Since the publication of the SYNTAX score II, several studies have provided independent data that have corroborated its ndings as detailed in the following sections.

ImpairedLVEF

A subanalysis of the Surgical Treatment of Ischemic Heart Failure (STICH) trial demonstrated that in subjects with more advanced ischaemic cardiomyopathy, more extensive CAD, and worse myocardial dysfunction and remodelling, a net longer- term prognostic benet was seen for CABG compared to optimal medical therapy up to 10years, despite the short- term (30- day) mortality risk being higher with CABG. Although the 10- year mortality was high irrespective of whether the patient was revascularized or not, the margin of mortality benet was clinically relevant for CABG (10- year mortality:58.9% (CABG) vs 66.1% (medical therapy); HR 0.84, 95% CI

0.73– 0.97; P =0.02) validating the concept that CABG provides a protective role in coronary vessels in patients with complex CAD, particularly that associated with severely impaired LVEF.

Another important issue is the potential value of revascularization if the area of myocardium supplied by the coronary vessel is infarcted and non- viable. Acounter argument to this assumption is that the presence of a chronic total occlusion (CTO) has been shown in multiple registries to be a powerful independent predictor of mortality in patients presenting with an acute myocardial infarction., e

underlying principle is that a CTO of, for instance, the le anterior descending artery (LAD), may be dependent on collateralization from the right coronary artery to remain viable., In such a scenario, acute occlusion of the right coronary artery would jeopardize the blood supply to both territories with ensuing cardiogenic shock. Likewise, if the LAD was not occluded, it potentially could collateralize an occluded right coronary artery irrespective of whether the LAD territory was viable. In essence, patency of all the major epicardial vessels is essential to ensure they are able to provide (and receive) collateral blood supply (if present) from other coronary vessels in multivessel disease, particularly since well- developed coronary collateral arteries have been shown to reduce potential myocardial infarct size and to improve survival.

Chronic kidneydisease

SYNTAX demonstrated that the severity of chronic kidney disease (CKD) had a substantial impact on decision- making between CABG and PCI, with worsening kidney function associated with a greater likelihood for a prognostic benet from CABG., Consequently, as discussed earlier, patients would require substantially lower SYNTAX scores to achieve equipoise between CABG and PCI for long- term mortality, most likely due to the greater likelihood of the existing presence or future development of vulnerable plaque., Importantly no restrictions were placed on the severity of CKD in SYNTAX, due to its all- comers design. ese ndings are supported by a population- based study of patients with CKD and multivessel coronary disease from the Ontario provincial registry demonstrating that CABG is associated with improved early and late mortality compared to PCI.

Conversely, in FREEDOM, the presence of CKD— dened as an estimated glomerular ltration rate less than 60 mL/ min— was shown to have a similar impact on clinical outcomes at a median follow- up of 3.8 years, irrespective of the presence or absence of CKD (HRs for the eect of CABG against PCI on MACCE:with CKD, HR 0.73, 95% CI 0.50– 1.05; without CKD, HR 0.76, 95% CI

0.58– 1.00; interaction, P = 0.83). Importantly, as FREEDOM excluded patients with severe CKD (estimated glomerular ltration rate <15 mL/ min or requiring dialysis), its applicability to diabetics with severe CKD is limited.

Unprotected left main coronary artery disease— EXCEL

e recently reported Evaluation of XIENCE Everolimus Eluting Stent Versus Coronary Artery Bypass Surgery for Eectiveness of Le Main Revascularization (EXCEL) trial randomly assigned 1905 patients with ULMCA with low to intermediate anatomical complexity (anatomical SYNTAX score <33) to undergo CABG (n=957) or PCI with contemporary DES (n=948)., To mirror clinical practice, site- reported anatomical SYNTAX scores were used as enrolment criteria. Apart from the anatomical entry criteria of EXCEL— patients with up to intermediate anatomical complexity CAD (SYNTAX score <33) in keeping with the le main subgroup ndings of SYNTAX— the design was all- comers to prevent selection that had plagued CABG vs. PCI trials prior to SYNTAX., EXCEL demonstrated at least an equipoise for the primary endpoint (composite outcome of all- cause death, myocardial infarction, and stroke) at a median follow- up of 3years (interquartile range 2.4– 3years, minimum follow- up of 2years):CABG 14.7%, PCI 15.4%

9 Evidence basis fordecision-making betweencoronary artery bypass grafting and percutaneous coronaryintervention 85

Log HR

SYNTAX score

Log HR

Age (years) CrCl (mL/min) LVEF (%)

Log HR

Yes

https://t.me/medicina_free

PCI CABG

–1

–2

–1

–2

–1

–2

3VD

20 40 60

Left main

PCI CABG

Diabetes

60 70 80 90

Sex

LMS

03090 10060 10 20 50 6030 40

No Yes

COPD

PVD

Fig.9.6 Predictor effects for CABG and PCI in the SYNTAX score II for long- term mortality in the SYNTAX trial. These are represented visually as a log

hazard ratio (HR) for CABG and PCI on the y- axis for each predictor. Each predictor is expressed on the x- axis continuously (upper) or categorically (lower), for a person of mean baseline characteristics. Diabetes is included (highlighted in red) to illustrate its absence of interaction when included in the analyses. Note the differing gradients of the hazards for PCI and CABG, leading to the hazards crossing at an anatomical SYNTAX score of 15. At this cross- over point of hazards, the long- term mortality risk is comparable between CABG and PCI. This threshold of cross- over of hazards will vary according to the level of other variables, namely being lower for female sex, reduced LVEF, and younger age, and higher for COPD, ULMCA disease, and older age. As both peripheral vascular disease (PVD) (P=1.00) and diabetes (P=0.67) lacked an interaction effect, as indicated by almost parallel HRs (i.e. comparable increase in long- term mortality risk), their presence would have no impact on decision- making between CABG and PCI.

Reproduced from Farooq V, van Klaveren D, Steyerberg EW, etal. Anatomical and clinical characteristics to guide decision making between coronary artery bypass surgery and percutaneous coronary intervention for individual patients:development and validation of SYNTAX score II. Lancet. 2013;381(9867):639– 50 with permission from Elsevier.

(P=0.02 for non- inferiority; HR 1.00, 95% CI 0.79– 1.26; P=0.98 for superiority). However at 5years follow up, despite similar outcomes between CABG and PCI for the primary endpoint— CABG 19.2%, PCI 22% (dierence 2.8%, 95% CI - 0.9 to 6.5, p=0.130, P=0.02 for non- inferiority; HR 1.00, 95% CI 0.79– 1.26; P = 0.98 for superiority)— survival curves diverged in favour of CABG (CABG 9.9% vs. PCI 13.0%, dierence 3.1%; 95% CI, 0.2 to 6.1).

Notably, when the core laboratory SYNTAX scores were assessed in EXCEL, it was found that approximately a quarter of the patients (24.2%) actually had high anatomical SYNTAX scores (≥33). e site- reported anatomical SYNTAX scores in EXCEL of low (≤22)

in 60.5%, and intermediate (23– 32) in 39.5% were at variance with the core laboratory- reported scores being, respectively, 35.8%, and

40.0% and high (≥33) in 24.2%. Asimilar phenomenon had also previously occurred in the SYNTAX trial, in which there was a substantial disparity in the site versus core laboratory reporting of the anatomical SYNTAX score. It should, however, be emphasized that within SYNTAX, this eect was mitigated when the clinical variables determined in the SYNTAX score II were incorporated, again emphasizing the importance of clinical factors (in addition to coronary anatomy) in decision- making between CABG and PCI on the grounds of predicted long- term mortality.

SECTION 2 Treatment ofcoronary artery disease

100

CrCl (mL/min)

https://t.me/medicina_free

4-year mortality (%)

0.6%

Points

Syntax score

Age (years)

40 50 60 70 80 40 50 8060 70

90 60 30 90 3060

LVEF (%)

50040 20

Left main

Sex*

COPD

PVD

6.8%

1.3%

20 40 60

00+246810 1214

30 50 2040 30

CABG

31.5%

15.1%

Total points

16182022 24262830

58.4%

0246 8101214

80 100

PCI

16182022 24262830

0102030405060

SYNTAX Score II questions and calculator outputs:

(a) Anatomical SYNTAX (points): 48 Age (years): 74 CrCl (ml/min): 49 LVEF (%): 50 Left main: No Sex: Female COPD: No PVD: No

SSII PCI (points): 51 SSII CABG (points): 28 4-year predicted mortality PCI (%): 33 4-year predicted mortality CABG (%): 6

Treatment recommendation CABG

(b) Anatomical SYNTAX (points): 16 Age (years): 75 CrCl (ml/min): 62 LVEF (%): 70 Left main: No Sex: Male COPD: Yes PVD: Yes

SSII PCI (points): 48 SSII CABG (points): 60 4-year predicted mortality PCI (%): 28 4-year predicted mortality CABG (%): 57

Treatment recommendation PCI

(c) Anatomical SYNTAX (points): 20 Age (years): 49 CrCl (ml/min): 99 LVEF (%): 55 Left main: No Sex: Male COPD: No PVD: No

SSII PCI (points): 19 SSII CABG (points): 12 4-year predicted mortality PCI (%): 3 4-year predicted mortality CABG (%): 2

Treatment recommendation CABG orPCI

Fig.9.7 The SYNTAX score II nomogram for bedside application. Total number of points for eight factors can be used to accurately predict long- term

(4- year) mortality for the individual patient proposing to undergo CABG or PCI (left). Case examples are illustrated (right). An online calculator is now available for clinical use (www.syntaxscore.com). PVD, peripheral vascular disease.

Although the results of EXCEL essentially corroborate the ndings of SYNTAX (primary endpoint) for patients with ULMCA, given the heterogeneity of anatomical complexity and high- risk patient subgroups recruited in EXCEL, even longer- term follow- up (at least 10years) may be necessary to fully understand the impact of ULMCA disease on decision- making between CABG and PCI. It is noteworthy that at 4years, clinical outcomes in the EXCEL trial appear to be diverging in favour of CABG (Fig. 9.4), despite the primary outcome favouring PCI at 30 days. At 30days, the primary outcome occurred in 7.9% of CABG patients versus 4.9% of PCI patients (P <0.001) largely driven by periprocedural myocardial infarction (dened dierently than in SYNTAX).

Whether the inclusion of more anatomically complex subjects (i.e. high anatomical SYNTAX scores (>32))— not intended by protocol to be recruited in EXCEL— to have impacted on the results of EXCEL is currently not known. Moreover, the disparity between site- and core laboratory- reported anatomical SYNTAX scores identied in both the original SYNTAX trial and EXCEL, highlights the need for a more objective assessment of anatomical coronary complexity and is discussed in the section entitled ‘Non- invasive imaging to guide decision- making’.

Unprotected left main coronary artery disease— NOBLE

Contrary to the ndings of SYNTAX and EXCEL, the Percutaneous Coronary Angioplasty Versus Coronary Artery Bypass Graing in Treatment of Unprotected Le Main Stenosis (NOBLE) trial reported diverging early results in favour of CABG. NOBLE randomly assigned 1201 patients with ULMCA to undergo CABG (n=603) or PCI with predominantly contemporary DES (n=598)., Notably, NOBLE did not use the anatomical SYNTAX score as entry criteria and instead was reliant on other criteria, namely, visual assessment of le main stenosis diameter greater than or equal to 50% or fractional ow reserve of 0.80 or less in the le main coronary artery ostium, mid- sha, or bifurcation non- complex lesions, and no more than three additional non- complex coronary artery lesions. Complex lesions were dened as CTOs, bifurcation lesions requiring a two- stent technique, or lesions with calcied or tortuous vessel morphology. It is notable that systematic screening logs were not available in 31 of the 36 centres which eventually randomized 695/ 1201 (57.9%) patients, whereas in the remaining ve centres 982 patients were screened, with just over half the screened patients (506/ 982 (51.2%)) randomized. In the latter group, the most common

9 Evidence basis fordecision-making betweencoronary artery bypass grafting and percutaneous coronaryintervention 87

PCI CABG

No. at risk

476 522

PCI CABG

No. at risk

452 480

Death, stroke, or myocardial infarction Death from any cause(a)

(c)

(b)

https://t.me/medicina_free

100

Patients (%)

948 896 875 957 868

100

Patients (%)

6 12 24 36

Hazard ratio, 1.00 (95% CI, 0.79–1.26) P = 0.98

6 12 24

850 817

6 12 24 36

836

Hazard ratio, 0.77 (95% CI, 0.43–1.37) P = 0.37

14.7%

Month

15.4%

784 763

2.9%

2.3%

445 468

100

Patients (%)

No. at risk

PCI CABG

100

Patients (%)

948 933 921 957 933

6 12 24 36

Hazard ratio, 1.34 (95% CI, 0.94–1.91) P = 0.11

6 12 24 36

Month

898

910

889

Myocardial infarction(d)Stroke

6 12 24 36

Hazard ratio, 0.93 (95% CI, 0.67–1.28) P = 0.64

8.2%

5.9%

839 835

8.3%

8.0%

948 930 915 957 922

899

6 12 24

Month

893 880

839 823

473 511

No. at risk

PCI CABG

948 900 882 957 879

CABG (N = 957)PCI (N = 948)

6 12 24 36

Month

846

857 830

805 776

Fig.9.8 Time- to- event curves for the primary composite endpoint (death, MI, stroke) and its components from the EXCEL Trial investigating patients

with ULMCA disease at a median follow- up of 3years. Panel (a)shows the results of the analysis of the primary composite endpoint of death, stroke, or myocardial infarction at 3years. Results of analyses of the components of the primary endpoint are shown in (b)death from any cause, (c)stroke, and (d)myocardial infarction. Event rates were based on Kaplan– Meier estimates in time- to- ﬁrst- event analyses. Hazard ratios are for the patients who underwent percutaneous coronary intervention (PCI) with everolimus- eluting stents. The rates of stroke and myocardial infarction are non- hierarchical (i.e. fatal and non- fatal events were included). In each panel, the inset shows the same data on an enlarged y- axis. CABG denotes coronary- artery bypass grafting.

Reproduced fromStone GW, Sabik JF, Serruys PW, etal. Everolimus- Eluting Stents or Bypass Surgery for Left Main Coronary Artery Disease [published correction appears in N Engl J Med. 2019 Oct 31;381(18):1789]. N Engl J Med. 2016;375(23):2223– 35. doi:10.1056/ NEJMoa1610227 with permission fromMassachusetts Medical Society

reasons for non- enrolment were consideration that patients were not suitable for CABG or PCI (239/ 982 (24.3%)), greater than three non- complex lesions (94/ 982 (33.3%)), and/ or the presence of any complex lesions (212/ 982 (33.3%)). Furthermore, enrolment in NOBLE was slow— over a 6- year period— with 11% of patients receiving rst- generation DESs. Given that the event rate was lower than anticipated in NOBLE, the investigators changed the primary endpoint from 5years to a median of 3.1years (interquartile range

2.0– 5.0) with all patients followed up for at least 1year which may have had an impact on the reporting of the trial.

Five- year MACCE (a composite of all- cause mortality, non- procedural myocardial infarction, any repeat coronary revascularization, and stroke) in NOBLE was 29% for PCI and 19% for CABG, HR 1.48 (95% CI 1.11– 1.96), exceeding the limit for noninferiority, with CABG signicantly better than PCI (P=0.0066). Notably outcomes of MACCE were predominantly driven by nonprocedural myocardial infarction and repeat revascularization (all- cause mortality 12% vs 9% (HR 1.07, 95% CI 0.67– 1.72; P= 0.77), non- procedural myocardial infarction 7% vs 2% (HR

2.88, 95% CI 1.40– 5.90; P =0.0040), all- cause revascularization

<<< < Предыдущая 1 2 3 4 5 6 7 8 9 1011 / 5011 12 13 14 15 16 17 18 19 20 21 22 23 24 25 > Следующая >>>

Соседние файлы в папке Библиотека им академика М.И. Перельмана

#
29.08.202681 Мб0Книга_3609_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202679 Мб0Книга_3610_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202676 Мб0Книга_3611_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202674 Мб0Книга_3612_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202674 Мб0Книга_3613_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202673 Мб0Книга_3614_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202673 Мб0Книга_3615_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202673 Мб0Книга_3616_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202672 Мб0Книга_3617_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202671 Мб0Книга_3618_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202671 Мб0Книга_3619_Библиотеки_им_академика_М_И_Перельмана.pdf