TITLE: TITLE: Percutaneous Coronary...

TITLE:TITLE:TITLE:TITLE: Percutaneous Coronary InterventionPercutaneous Coronary InterventionPercutaneous Coronary InterventionPercutaneous Coronary Intervention as an Alternative as an Alternative as an Alternative as an Alternative

to Coronary Artery Bypass Graftingto Coronary Artery Bypass Graftingto Coronary Artery Bypass Graftingto Coronary Artery Bypass Grafting in Patients with in Patients with in Patients with in Patients with

Diabetes MellitusDiabetes MellitusDiabetes MellitusDiabetes Mellitus and Multiand Multiand Multiand Multi----vessel Disease vessel Disease vessel Disease vessel Disease

AUTHOR:AUTHOR:AUTHOR:AUTHOR: Judith Walsh, MD,Judith Walsh, MD,Judith Walsh, MD,Judith Walsh, MD, MPHMPHMPHMPH

Professor of MedicineProfessor of MedicineProfessor of MedicineProfessor of Medicine

Division of General Internal MedicineDivision of General Internal MedicineDivision of General Internal MedicineDivision of General Internal Medicine

Department of MedicineDepartment of MedicineDepartment of MedicineDepartment of Medicine

University of California San FranciscoUniversity of California San FranciscoUniversity of California San FranciscoUniversity of California San Francisco

PUBLISHER:PUBLISHER:PUBLISHER:PUBLISHER: California Technology Assessment ForumCalifornia Technology Assessment ForumCalifornia Technology Assessment ForumCalifornia Technology Assessment Forum

DATE OF DATE OF DATE OF DATE OF

PUBLICATION:PUBLICATION:PUBLICATION:PUBLICATION: March March March March 6666, 2013, 2013, 2013, 2013

PLACE OF PLACE OF PLACE OF PLACE OF

PUBLICATION:PUBLICATION:PUBLICATION:PUBLICATION: San Francisco, CASan Francisco, CASan Francisco, CASan Francisco, CA

PERCUTANEOUS CORONARPERCUTANEOUS CORONARPERCUTANEOUS CORONARPERCUTANEOUS CORONARY INTERVENTION AS ANY INTERVENTION AS ANY INTERVENTION AS ANY INTERVENTION AS AN ALTERNATIVE TO CORONALTERNATIVE TO CORONALTERNATIVE TO CORONALTERNATIVE TO CORONARY ARY ARY ARY

ARTERY BYPASS GRAFTIARTERY BYPASS GRAFTIARTERY BYPASS GRAFTIARTERY BYPASS GRAFTING IN PATIENTS WITH NG IN PATIENTS WITH NG IN PATIENTS WITH NG IN PATIENTS WITH DIABETES MELLITUS ANDIABETES MELLITUS ANDIABETES MELLITUS ANDIABETES MELLITUS AND MULTID MULTID MULTID MULTI----

VESSEL DISEASEVESSEL DISEASEVESSEL DISEASEVESSEL DISEASE

A Technology Assessment

IntroductionIntroductionIntroductionIntroduction

The California Technology Assessment Forum is requested to review the

scientific evidence for the use of percutaneous coronary intervention as an

alternative to coronary artery bypass grafting in patients with diabetes mellitus.

This topic is being addressed because of recent publication of the Future

Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal

Management of Multi-Vessel Disease (FREEDOM) trial. This is the first time that

CTAF has addressed this topic.

BackgroundBackgroundBackgroundBackground

Coronary heart disease (CHD) is the number one cause of death in both men

and women in the U.S. Untreated CHD typically leads to progressive angina,

myocardial infarction, left ventricular (LV) dysfunction and congestive heart failure

(CHF) and sudden death. The goals of therapy in CHD are alleviation of anginal

symptoms, to delay or prevent progression of CHD and to prevent myocardial

infarction (MI) or death.

CHD treatment typically starts with medical therapy, including aggressive risk

factor reduction. Therapy includes aspirin, reaching treatment goals for

hypertension and hyperlipidemia, smoking cessation, and for diabetics, control of

serum glucose.

Coronary heart disease is a significant contributor to morbidity and mortality

in patients with diabetes mellitus. CHD is more common in diabetics than in non-

diabetics, and it is more likely to be multi-vessel. Diabetics are more likely to have

silent ischemia compared to patients without diabetes. In addition, diabetics with

CHD have lower survival rates than patients with CHD who do not have diabetes.

Diabetic and non-diabetic patients with multi-vessel coronary artery disease

are often considered for revascularization. In the U.S., approximately 700,000

patients undergo revascularization each year.1,2 The two main indications for

revascularization are 1) unacceptable angina and 2) where a survival benefit might

be expected from revascularization.

RevascularizationRevascularizationRevascularizationRevascularization: Coronary Artery Bypass Graft: Coronary Artery Bypass Graft: Coronary Artery Bypass Graft: Coronary Artery Bypass Grafting ing ing ing

The first revascularization treatment developed and used was coronary

artery bypass grafting (CABG). CABG relieves symptoms and improves survival

compared with medical management in some patients with stable angina. The

Coronary Artery Surgery Study (CASS) which was done in the late 1970s and early

1980s showed that more patients remained symptom free after CABG than with

medical therapy at one year (66% vs 30%) and at five years (63% vs 38%).3

Although for many patients with coronary artery disease (CAD) who undergo

CABG, there is no mortality benefit,4-7 certain subgroups do have a mortality benefit

from CABG. Patients who have a mortality benefit from CABG compared with

medical therapy include those with left main disease or left main equivalent disease,

three vessel coronary disease especially in the presence of reduced ejection fraction

(EF) and two vessel disease when there is a <75% stenosis in the left anterior

descending artery (LAD) proximal to the first septal artery.6,8-11

The 2011 Recommendations of the American College of Cardiology

Foundation/American Heart Association ACCF/AHA on CABG recommend a strong

preference for CABG in the following groups of patients:

• Unprotected left main coronary artery stenosis (≥50%);

• Significant (>70% stenosis) three vessel disease with or without proximal LAD

disease;

• Two vessel disease with proximal LAD disease (>75% stenosis in the LAD

proximal to the first major septal artery); and

• Patients with one or more significant coronary artery stenosis amenable to

revascularization and disabling angina while on maximal medical therapy12

A weak recommendation for CABG is made for the following groups:

• Two vessel disease without significant proximal LAD disease but with

extensive ischemia;

• Significant proximal LAD disease and evidence of extensive ischemia if a left

internal mammary artery bypass graft can be placed; and

• Mild to moderate left ventricular systolic dysfunction (EF: 35 - 50%) and

significant multi-vessel CAD or proximal LAD stenosis when viable

myocardium is present in the region of intended revascularization.12

Revascularization recommendations for patients with diabetes are essentially

the same as for those patients who do not have diabetes. However the short term

and long term results with either PCI or CABG are typically worse in diabetics than

in nondiabetics.13

Revascularization: Percutaneous Coronary InterventionsRevascularization: Percutaneous Coronary InterventionsRevascularization: Percutaneous Coronary InterventionsRevascularization: Percutaneous Coronary Interventions

Percutaneous coronary interventions (PCIs) are therapeutic procedures

where a balloon or catheter is inserted into a coronary artery. PCIs are non-surgical

treatments and are potentially less invasive options for the treatment of CAD when

compared with CABG. PCI is typically preferred to CABG for single vessel disease,

but its role in more severe forms of CAD has been less clear.

Initial PCI procedures included balloon angioplasty where a balloon was

used to open up the stenotic artery. Although balloon angioplasty was the initial

type of PCI, high rates of restenosis led to adding a stent after the artery was

opened. The initial stents that were used were bare metal stents (BMS), but BMS

were still associated with a significant restenosis risk.

The current standard for PCI is angioplasty with the addition of a drug

eluting stent (DES). DES have been shown to reduce the rate of restenosis

compared with BMS. They inhibit neointimal hyperplasia, a response that may be

stimulated by BMS. DES include a standard metallic stent, which has a polymer

coating and an anti-restenotic drug. The drug is mixed within the polymer and is

released over a period of days for up to a year after the procedure. There are

currently four types of approved DES. They include sirolimus-eluting, paclitaxel-

eluting, zotarolimus-eluting and everolimus-stents. Sirolimus is a macrocyclic triene

antibiotic with immunosuppressive and anti-proliferative properties They were

developed to prevent the proliferation of smooth muscle cells. Paclitaxel interferes

with microtubule function that are responsible for chromosome segregation during

cell division. They also prevent smooth muscle proliferation. Everolimus is a

sirolimus derivate as is zotarolimus. DES have similar safety profiles when

compared with BMS. In terms of efficacy, DES are preferred given that they

significantly lower the rate of target lesion revascularization when compared with

BMS.

Currently the standard of care when performing PCI is to use a DES rather

than a BMS in most patients given the evidence for increased efficacy with DES.

When comparing CABG to PCI, many of the earlier studies compared CABG to

balloon angioplasty or BMS, whereas the more recent studies compare CABG to

DES.

RevascularRevascularRevascularRevascularization in Diabeticsization in Diabeticsization in Diabeticsization in Diabetics

Among patients undergoing revascularization, approximately 25-30% have

diabetes. The indications for revascularization are similar in diabetics and non-

diabetics, although the outcomes in patients with diabetes are typically worse.

Most of the studies in diabetics comparing PCI with CABG have been

subgroup analyses of larger studies. Given that diabetics have worse short and

long term outcomes with any revascularization, it is important to compare the

efficacy of CABG with the efficacy of PCI specifically in diabetic populations. The

goal of this assessment is to evaluate PCI as an alternative to CABG in diabetics with

multi-vessel CAD.

TECHNOLOGY ASSESSMENT (TA)TECHNOLOGY ASSESSMENT (TA)TECHNOLOGY ASSESSMENT (TA)TECHNOLOGY ASSESSMENT (TA)

TA Criterion 1:TA Criterion 1:TA Criterion 1:TA Criterion 1: The technology must have final approval from the The technology must have final approval from the The technology must have final approval from the The technology must have final approval from the appropriate appropriate appropriate appropriate

government regulatory bodies.government regulatory bodies.government regulatory bodies.government regulatory bodies.

The U.S. Food and Drug Administration (FDA) defines a coronary stent as a

device made of a metal scaffold placed via a delivery catheter during PCI into the

coronary artery or saphenous vein graft to widen or maintain the opening of the

narrowed coronary vessels. Coronary artery stents are classified as Class III devices

and approved only via the pre-market approval (PMA) process. Manufacturers with

FDA approved coronary artery stents and systems include Cordis Corporation, - a

subsidiary of Johnson & Johnson, Co., Abbot Vascular, Boston Scientific

Corporation, Medtronic, and Medinol, Ltd.

TA Criterion 1 is met.

TA Criterion 2:TA Criterion 2:TA Criterion 2:TA Criterion 2: The scientific evidence must permit conclusions concerning The scientific evidence must permit conclusions concerning The scientific evidence must permit conclusions concerning The scientific evidence must permit conclusions concerning

the effectiveness of ththe effectiveness of ththe effectiveness of ththe effectiveness of the technology regarding health e technology regarding health e technology regarding health e technology regarding health

outcomes.outcomes.outcomes.outcomes.

The Medline database, Cochrane clinical trials database, Cochrane reviews

database and Database of Abstracts of Reviews of Effects (DARE) were searched

using the search terms coronary artery bypass, CABG, percutaneous coronary

intervention, PCI stents and coronary artery disease, and diabetes mellitus or

diabetes. The search was performed for the period from database inception

through December, 2012. The bibliographies of systematic reviews and key articles

were manually searched for additional references and references were requested

form the device manufacturer. The abstracts of citations were reviewed for

relevance and all potentially relevant articles were reviewed in full.

Inclusion criteria were:

• Study had to evaluate PCI and CABG in patients with diabetes and multi-

vessel disease;

• Study had to measure clinical outcomes;

• Included only humans; and

• Published in English as a peer reviewed article

Studies were excluded if they only focused on non-clinical outcomes.

A total of 373 potentially relevant articles were identified. These 373

abstracts were evaluated and 331 were excluded. Reasons for exclusion included

not addressing the study question, not reporting clinical outcomes, not comparing

PCI to CABG. After evaluation of the remaining 42 abstracts, exclusion of duplicate

publications and review of articles, a total of fourteen published clinical trials are

included in this evaluation.

Details of the clinical trials are described in Table 1. There were five trials

comparing CABG to balloon angioplasty.14-18 These five trials included a total of 640

diabetic patients. In all these studies, diabetics were a subgroup of the total

number of patients. An additional five studies compared BMS with CABG.19-23

These studies included a total of 684 diabetic patients who were again a subgroup

of all patients. Four trials compared DES with CABG.22,24-32 These studies included

3,021 patients, 1,900 of whom came from one study, the FREEDOM trial.27,32 In two

of the studies, diabetics were a subgroup of the total number of patients

included.22,26,29-31 Two of the studies included only diabetics.27,28,32

Study outcomes included mortality, non-fatal MI, Q wave MI, CVA and rates

of revascularization. Composite endpoints were frequently used. Typical

composite endpoints included MACCE (major cardiovascular and cerebrovascular

events) defined as death, CVA, MI and repeat revascularization, and MACE (major

cardiovascular events) defined as death, MI and repeat revascularization. Other

included outcomes were angina class at one year and freedom from angina

pectoris at one year.

Level of Evidence: 1,2

TA Criterion 2 is met.

Table 1: Description of Studies of PCI vs CABG in Patients with DiabetesTable 1: Description of Studies of PCI vs CABG in Patients with DiabetesTable 1: Description of Studies of PCI vs CABG in Patients with DiabetesTable 1: Description of Studies of PCI vs CABG in Patients with Diabetes MellitusMellitusMellitusMellitus

NameNameNameName of of of of

studystudystudystudy

Diabetics are a Diabetics are a Diabetics are a Diabetics are a

subgroup?subgroup?subgroup?subgroup?

NNNN

DDDDiabeticsiabeticsiabeticsiabetics

Inclusion CriteriaInclusion CriteriaInclusion CriteriaInclusion Criteria InterventionInterventionInterventionIntervention Main OutcomesMain OutcomesMain OutcomesMain Outcomes

Balloon Angioplasty vs CABGBalloon Angioplasty vs CABGBalloon Angioplasty vs CABGBalloon Angioplasty vs CABG

BARI18

Yes 353 Multi-vessel CAD and

candidates for PTCA or

CABG

Balloon angioplasty

vs CABG

All cause mortality

New MI

CABRI17

Yes 124 Multi-vessel CAD and

eligible for revascularization

PTCA vs CABG Mortality and angina class at one

year

EAST14 Yes 90 Multi-vessel CAD who could

undergo either procedure

PTCA vs CABG Composite: death, Q wave MI or

major ischemic thallium defect at

three year follow-up

GABI15

Yes 41 Symptomatic multi-vessel

disease

PTCA vs CABG Freedom from angina pectoris at

one year

RITA-116 Yes 62 Single or multi-vessel

disease and

revascularization

appropriate

PTCA vs CABG Death or non-fatal MI

Bare Metal Stenting vs CABG Bare Metal Stenting vs CABG Bare Metal Stenting vs CABG Bare Metal Stenting vs CABG

ARTS-I22 Yes 208 Multi-vessel CAD including

LAD and at least one other

lesion in another major

epicardial artery

BMS vs CABG Composite: MACCE -death, CVA, MI

and repeat revascularization

AWESOME20 Yes 144 Medically refractory

unstable angina and at high

risk for CABG

BMS vs CABG 30 day, six month and 36 month

survival

SOS23 Yes 142 Revascularization clinically PCI (any Mortality

NameNameNameName of of of of

studystudystudystudy

Diabetics are a Diabetics are a Diabetics are a Diabetics are a

subgroup?subgroup?subgroup?subgroup?

NNNN

DDDDiabeticsiabeticsiabeticsiabetics

Inclusion CriteriaInclusion CriteriaInclusion CriteriaInclusion Criteria InterventionInterventionInterventionIntervention Main OutcomesMain OutcomesMain OutcomesMain Outcomes

indicated and appropriate

by either strategy

commercially

available BMS) vs

CABG

Rate of repeat revascularization

ERACI II19

Yes 78 Multi-vessel CHD and

clinical indication for

revascularization

PCI with stent

placement vs CABG

Freedom from major adverse

cardiovascular events (MACE) at 30

days, one year, three years and five

years

MASS II21 Yes 115 Multi-vessel CAD and

eligible for each strategy

PCI with stent vs

CABG

Composite: Mortality, Q wave MI,

and refractory angina requiring

revascularization

Drug eluting stents vs CABGDrug eluting stents vs CABGDrug eluting stents vs CABGDrug eluting stents vs CABG

ARTS-II22,24,25

Yes 159 Multi-vessel CAD including

LAD and at least one other

lesion in another major

epicardial artery

Sirolimus eluting

stent single arm

compare with

historical controls

Composite: MACCE -death, CVA, MI

and repeat revascularization

CARDia28

No 510 Diabetic patients with multi-

vessel or complex single

vessel CAD

PCI plus stenting

(69% sirolimus and

31% BMS) vs CABG

Composite: all cause mortality, MI

and stroke

SYNTAX26,29-31

Yes:

prespecified

452 Left main and or three

vessel disease

TAXUS express DES

(paclitaxel) vs

CABG

Composite: all cause mortality, CVA,

MI or repeat revascularization

FREEDOM27,32

No 1,900 Multi-vessel coronary

disease suitable for either

PCI or CABG

Drug eluting stent

(sirolimus or

paclitaxel)

Composite: all cause mortality, non-

fatal MI and non-fatal stroke

ARTS-I: Arterial Revascularization Study I

AWESOME: Angina With Extremely Serious Operative Mortality Evaluation

BARI: Bypass Angioplasty Revascularization Investigation

CABG: Coronary Artery Bypass Graft

CABRI: Coronary Angioplasty versus Bypass Revascularization

CAD: Coronary Artery Disease

CARDia: Coronary Artery Revascularization in Diabetes

CHD: Coronary Heart Disease

EAST: Emory Angioplasty vs Surgery Trial

ERACI II: Argentine Randomized Study-Coronary Angioplasty with Stenting Versus Coronary Bypass Surgery in Multi-

Vessel Disease

FREEDOM: Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multi-Vessel

Disease

GABI: German Angioplasty Bypass Surgery Investigation

MACCE: Major Adverse Cardiac and Cerebrovascular Events

MACE: Major Adverse Cardiac Events

MASS II: Medicine, Angioplasty or Surgery Study

MI: Myocardial Infarction

PCI: Percutaneous Coronary Intervention

PTCA: Percutaneous Transluminal Coronary Angioplasty

RITA-1: Randomized Intervention Treatment of Angina

SOS: Surgery or Stent Study

SYNTAX: Synergy between PCI with Taxus and Cardiac Surgery

Table 2: Outcomes of Studies of PCI vs CABG in Patients with Diabetes MellitusTable 2: Outcomes of Studies of PCI vs CABG in Patients with Diabetes MellitusTable 2: Outcomes of Studies of PCI vs CABG in Patients with Diabetes MellitusTable 2: Outcomes of Studies of PCI vs CABG in Patients with Diabetes Mellitus

NameNameNameName Length of Length of Length of Length of

followfollowfollowfollow----upupupup

ResultsResultsResultsResults CommentsCommentsCommentsComments

Balloon Balloon Balloon Balloon AAAAngioplasty vs CABGngioplasty vs CABGngioplasty vs CABGngioplasty vs CABG

BARI18

5.4 years Five year survival 80.6% for CABG and 65.5% for PTCA

(p=0.003)

CABRI One year Overall mortality at one year follow-up similar in both groups

(2.7% CABG and 3.9% PTCA: NS)

Diabetics not analyzed separately

EAST Three years Overall composite: 27.3% CABG vs 28.8% PTCA; NS


GABI Overall freedom from angina: 74% CABG vs 71% PTCA; NS Diabetics not analyzed separately

RITA-1 6.5 years Primary outcome: 5/29 PTCA vs 12/33 CABG: p=.055

Bare Bare Bare Bare MMMMetal etal etal etal SSSStententententttting vs CABG ing vs CABG ing vs CABG ing vs CABG

ARTS-I Five years MACCE higher in patients with BMS compared with CABG

(53.8% vs 23.4%:

p= 0.001)

AWESOME20 Three years

(36

months)

Survival at 36 months: 72% CABG vs 81% PCI: NS

SOS23 Six year 17.6% of PCI patients died vs 5.4% in CABG group (HR 3.53:

95% C.I. 1.14 to 10.95)

No difference in treatment effect

between diabetic and non-diabetic

subgroups

ERACI-II Five years PCI mortality 10% vs CABG mortality 10.2%: NS)

MASS-II Five years Overall composite: 21.2% in CABG group vs 32.7% in PCI

(p=0.0026)


Drug Drug Drug Drug EEEEluting luting luting luting SSSStents vs CABGtents vs CABGtents vs CABGtents vs CABG

NameNameNameName Length of Length of Length of Length of

followfollowfollowfollow----upupupup

ResultsResultsResultsResults CommentsCommentsCommentsComments

ARTS-II24,25

Onuma, 2010;

Five years MACCE lower in CABG than DES (23.4% vs 40.5%: p<0.001) Comparison with historical control

CARDia28

One year No difference in composite outcome (death/MI/stroke) 10.5%

CABG vs 13.0% PCI (HR 1.25: 95% C.I. 0.75,2.09: p=0.39)

Secondary outcome: death, MI stroke or revascularization

11.3% CABG vs 19.3% PCI (HR 1.77:95% C.I. 1.11-2.82: p=0.02)

When subgroup that received DES

(69%) compared with CABG, still

no difference

SYNTAX26,29-31

Three years No difference in composite safety endpoint at one

year(death/stroke/MI) between two groups

(10.3% CABG vs 10.1% DES; p=0.96)

Repeat revascularization rates higher with DES (20.3% vs

6.4%;p<0.0010

At three years, composite endpoint 22.9% CABG vs 27.0%

DES: p=0.002

FREEDOM32

3.8 years Composite outcome at five years more common in PCI

group: 26.6% in PCI and 18.7% in CABG: p=0.005

Stroke rate at five years more common in CABG group (5.2%

vs 2.4%: p=0.030)







CARDia: Coronary Artery Revascularization in Diabetes



ERACI II: Argentine Randomized Study-Coronary Angioplasty with Stenting Versus Coronary Bypass Surgery in Multi-

Vessel Disease

FREEDOM: Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multi-Vessel

Disease


MACCE: Major Adverse Cardiac and Cerebrovascular Events

MACE: Major Adverse Cardiac Events





RITA-1: Randomized Intervention Treatment of Angina



TA Criterion 3:TA Criterion 3:TA Criterion 3:TA Criterion 3: The technology must improve net health outcomes.The technology must improve net health outcomes.The technology must improve net health outcomes.The technology must improve net health outcomes.

In order to determine whether PCI improves net health outcomes, the

potential benefits and potential risks must be assessed.

Potential BenefitsPotential BenefitsPotential BenefitsPotential Benefits

CABG has been the standard technique used to treat obstructions in

coronary arteries. In order to get the blood to the myocardium, either veins

(typically the saphenous) or arteries (internal mammary) are used to bypass the

diseased vessels. CABG can relieve symptoms and can prolong life for some

individuals but is a major surgical procedure, requiring sternotomy and associated

with surgical morbidity and mortality as well as a prolonged convalesence. The

main potential benefits of PCI are the ability to open a stenotic artery while

avoiding the need for a major operation with a sternotomy. The procedure

requires a groin incision using local anaesthetic and so avoids the need for major

surgery. Patients can often go home on the same day as the procedure.33 Thus the

main potential benefit is that revascularizaiton can be achieved without the patient

needing to undergo major cardiac surgery.

Potential RisksPotential RisksPotential RisksPotential Risks

1. 1. 1. 1. Long TermLong TermLong TermLong Term

The main long term risk with PCI is restsnosis, stent failure and the need for

revascularization. In the era of balloon angioplasty, the rate of restenosis was

significantly higher than it is currently in the DES era. The main reason for the

current use of DES is to reduce the risk of restenosis. Although restenosis can still

happen, the rates are lower than with BMS or PTCA. One large meta-analysis of 38

studies showed a reduction in target lesion revascularization with DES as compared

with BMS by about 12% at four year folllow-up.34 In a large registry study that

included patients with complex coronary lesions, the rate of target vessel

revascularization at two years was 7.4% for those who received DES compared with

10.7% for those who received BMS (p<0.001).35 In the FREEDOM trial, the

randomized controlled trial (RCT) of PCI with DES versus CABG in diabetics, the rate

of repeat revascularization events at one year was 12.6% in the PCI group vs 4.8% in

the CABG group (HR 2.74: 95% C.I. 1.91-3.89). Thus, although the rate of restenosis

requiring revascularization has decreased with the use of DES, it still remains a

significant long term risk associated with PCI.

2. 2. 2. 2. PeriPeriPeriPeri----ProceduralProceduralProceduralProcedural

PCI risks include those that are related to cardiac catheterization and

diagnostic angiography as well as those that are related to the particular stent

and/or wires that are used. Since the current standard of PCI includes the use of

stents rather than balloon angioplasty alone, the complications that are currently

seen are more likely to be stent related than those related to balloon angioplasty.

The risk of peri-procedural complications has decreased over time as devices

have improved, stents have been used and the use of anti-platelet therapy has

become more standard. In general rates of major peri-procedural complications

are low.

3. 3. 3. 3. Major complicationsMajor complicationsMajor complicationsMajor complications

An important complication which is frequently monitored is the need for

emergent CABG after PCI, if the PCI was not successful. The rate of emergent PCI

after CABG has been decreasing over time. In one study, it decreased from 2.95%

in 1979 to 1994 to 0.3% in 2000-2003.36 In the American College of Cardiology

National Cardiovascular Data registry, which includes over 100,000 PCI procedures,

performed between 1998 and 2000 of which 77% received stents, low rates of peri-

procedural complications, including in-hospital MI (0.4%), urgent CABG (1.9%) or

death (1.4%) were reported37.

4. 4. 4. 4. Coronary Artery CompCoronary Artery CompCoronary Artery CompCoronary Artery Compllllicationsicationsicationsications

Coronary artery complications include dissection, perforation, intramural

hematoma and occlusion of branch vessels. Dissection and resulting abrupt closure

are much less common in the DES era than they were with PTCA. Coronary artery

perforation is similarly much less common in the stent era but can still occur. In a

large series of over 10,000 PCIs performed from 1993-2001 (of which 6,836 received

stents ) the risk of perforation was 0.84%.38 The mortality rate after coronary artery

perforation is five to ten percent.39,40

5.5.5.5. Vascular ComplicationsVascular ComplicationsVascular ComplicationsVascular Complications

Vascular complications at the femoral artery insertion site can occur in about

six percent of patients41,42 Peripheral vascular complictaions after conventional and

complex percutaneous coronary interventional procedures42. include hematomas,

formation of pseudoaneurysms, occlusion, creation of AV fistulas and

retroperitoneal hematomas. Use of the radial artery (which is more compressible)

for access as compared with the femoral artery was associated with a reduced risk

of major bleeding in a 2009 meta-analysis,43 but not overall in a large RCT – Radial

vs Femoral Access for Coronary Angiography and Intervention in Patients with

Acute Coronary Syndromes (RIVAL), although there were some subgroups who did

achieve a bleeding reduction in RIVAL.44

6. 6. 6. 6. StrokStrokStrokStrokeeee

Stroke is a relatively rare complication of PCI with a rate of approximately

0.07% to 0.4% of procedures.45-47 Since stroke also occurs with the main alternative

to PCI, CABG, it is important to compare the risk of the two procedures. Most

individual trials have not shown a signfiicant difference in risk between the two

procedures, but most did not have adequate power to detect differences in that

relatively rare outcome. A recent meta-analysis compared the risk of stroke with

CABG to the risk with PCI.47 The meta-analysis included 10,944 patients in 19 trials.

The primary end point was 30 day risk of stroke. The 30 day risk of stroke was

signficantly higher in those who underwent CABG compared with those who

underwent PCI (1.20% vs 0.34%: OR 2.94: 95% C.I. 1.69 to 5.09: p = 0.0001). Similar

results were seen after a median follow-up of 12.1 months (1.83% vs 0.99%: OR

1.67:95% C.I. 1.09 to 2.56: p = 0.02). Thus although stroke remains a risk with PCI,

the risk is significantly lower than it would be with the main alternative, CABG.

7. 7. 7. 7. Other ComplicationsOther ComplicationsOther ComplicationsOther Complications

Other complications that can rarely occur as a result of PCI are

atheroembolic disease, acute kidney injury and anticoagulation associated bleeding.

SummarySummarySummarySummary

In summary, PCI has several potential benefits, especially in the current era

of PCI with DES. These benefits include revascularization without the need for a

major surgical procedure and its associated morbidity and mortality and need for

recuperation. The major risk is the potential need for revasascularizaiton after the

procedure. Although procedural complications can occur, overall the risks are

relatively low. Although stroke is a potentially important complication of PCI, the

risk of stroke is significantly lower than the risk seen with CABG. Thus, overall, net

health outcomes are improved with PCI, especially in the current era of DES.

TA Criterion 3 is TA Criterion 3 is TA Criterion 3 is TA Criterion 3 is metmetmetmet

TA Criterion 4:TA Criterion 4:TA Criterion 4:TA Criterion 4: The technology must be as beneficial as any established The technology must be as beneficial as any established The technology must be as beneficial as any established The technology must be as beneficial as any established

alternatives.alternatives.alternatives.alternatives.

The main established alternative to PCI is CABG. PCI treatments have

evolved over time. Initial studies compared balloon angioplasty with CABG. After

the introduction of stents, studies began to compare BMS with CABG. Finally, with

the introduction of DES, most recent studies have compared DES with CABG.

Early studies of Early studies of Early studies of Early studies of balloon angioplasty vs CABGballoon angioplasty vs CABGballoon angioplasty vs CABGballoon angioplasty vs CABG: subgroup analysis: subgroup analysis: subgroup analysis: subgroup analysis

Percutaneous transluminal coronary angioplasty (PTCA) was first introduced

in 1977.48 Initially it was used in patients with single vessel disease but over time

also began to be used in those with multi-vessel disease. In 1987, the NIH Heart,

Lung, and Blood Institute (NHLBI) initiated the Bypass Angioplasty Revascularization

Investigation (BARI). The goal of BARI was to test the hypothesis that a

revascularization strategy involving PTCA did not result in poorer clnical outcomes

than CABG at five year follow-up.49 BARI prespecified some subgroup analyses,

although evaluation of the impact on patients with diabetes was not prespecified.

A total of 1,829 patients with multi-vessel disease were randomized to either CABG

or PTCA and were followed for an average of 5.4 years. Of these, 353 had treated

diabetes at baseline. Overall, in the entire study cohort, the five year survival rate

was 89.3% for those assigned to CABG and 86.3% for those assigned to PTCA (p =

0.19). Among diabetics who were receiving diabetic treatment at baseline, the five

year survial was 80.6% for CABG and 65.5% for PTCA (p = 0.003). The results of this

study suggest that five year survival in diabetics may be better after CABG than

after PTCA, but since the analysis in diabetics was not a prespecified subgroup

analysis, these results should be seen as hypothesis generating rather than clearly

causal.

Four other studies of balloon angioplasty vs CABG all included some

diabetics.14-17 The number of diabetics in each study ranged from 41-124. However,

in only one of the studies - RITA-I: Randomized Intervention Treatment of Angina -

were diabetics analyzed separately. The primary outcome (death or MI) was not

statistically significantly different between the two groups although the numbers

were very small, given tht there were only 62 diabetic patients in the RITA-1 study.16

Bare Metal Stents Bare Metal Stents Bare Metal Stents Bare Metal Stents vvvvs CABGs CABGs CABGs CABG

The development of BMS was a significant advance over balloon angioplasty

in the treatment of coronary artery diseaes. Adding the BMS could reduce the

chance of restenosis by minimizing early arterial recoil and contraction. A total of

five studies have compared BMS to CABG. Four of these five studies reported

results in diabetics separately. The Medicine, Angioplasty or SMedicine, Angioplasty or SMedicine, Angioplasty or SMedicine, Angioplasty or Surgery Studyurgery Studyurgery Studyurgery Study IIIIIIII

((((MASS-II) included 115 diabetics but did not report the results in diabetics

separately.21

1. Arterial Revascularization Study I (ARTS1. Arterial Revascularization Study I (ARTS1. Arterial Revascularization Study I (ARTS1. Arterial Revascularization Study I (ARTS----I)I)I)I)

In ARTS-I, patients with multi-vessel CAD including the LAD and at least one

other lesion in another major epicardial artery were randomized to receive BMS vs

CABG. The main endpoint was a composite endpoint- death, MI and repeat

revascularizaiton or MACCE (major adverse cardiac and cerebrovascular events). In

the subgroup analysis of 208 diabetic patients, at five years the rate of MACCE was

higher in patients treated with BMS than in those treated with CABG (53.8% vs

23.4%: p = 0.001).

2. Angina With Extrememly Serious Operative Mortalit2. Angina With Extrememly Serious Operative Mortalit2. Angina With Extrememly Serious Operative Mortalit2. Angina With Extrememly Serious Operative Mortality Evaluationy Evaluationy Evaluationy Evaluation (AWESOME)(AWESOME)(AWESOME)(AWESOME)

In the AWESOME trial, patients with medically refractory unstable angina and

at high risk for CABG were randomized to either BMS vs CABG. Study outcomes

included 30 day, six month and 36 month survival. Among the 144 included

diabetics, 36 month survival was similar in the two groups (72% CABG vs 81% PCI:

NS).

3. Surgery or Stent (SOS) Trial 3. Surgery or Stent (SOS) Trial 3. Surgery or Stent (SOS) Trial 3. Surgery or Stent (SOS) Trial

The SOS trial randomized patients in whom revascularization was clinically

indicated and appropriate by either strategy to receive PCI with any commercially

available BMS vs CABG. The main study outcome was rate of repeat

revascularizaiton. A total of 142 diabetics were included in this study. At six year

follow-up, a total of 17/65 of the PCI patients had died vs 5.4% of those in the

CABG group (HR 3.53: 95% C.I. 1.14 to 10.95). There was no difference in treatment

effect between diabetic and non-diabetic subgroups.

4.4.4.4. Argentine Randomized StudyArgentine Randomized StudyArgentine Randomized StudyArgentine Randomized Study----coronary Angioplasty with Stentingcoronary Angioplasty with Stentingcoronary Angioplasty with Stentingcoronary Angioplasty with Stenting IIIIIIII (ERACI II)(ERACI II)(ERACI II)(ERACI II)

In the ERACI II trial, patients with multi-vessel CHD and clinical indications for

revascularization were randomized to either receive PCI with stent placement or

CABG. The main outcome was freedom from major adverse cardiovascular events

(MACE) at 30 days, one year, three years and five years. At five year follow-up,

mortaltiy among the 78 included diabetics was 10% in the PCI group vs 10.2% in the

CABG group, not significantly different between the two groups.

Drug Eluting Stents vs Drug Eluting Stents vs Drug Eluting Stents vs Drug Eluting Stents vs CABGCABGCABGCABG

Many of the earlier studies using either balloon angioplasty or BMS were

done before the current era where the standard for PCI to use DES. Four studies

have compared drug eluting stents and CABG for the treatment of multi-vessel

disease in patients with diabetes. A total of 3,021 patients have been included in

these four studies- 1,900 of the patients came from the FREEDOM study. Two of

the studies were subgroup analyses of larger studies22,24-26,29-31, and the other two

studies included only diabetics.32

1. ARTS1. ARTS1. ARTS1. ARTS----IIIIIIII

The ARTS-II study was a single arm study. All participants received DES.

ARTS I was a randomized controlled trial comparing surgery and BMS. Patients in

the ARTS-II trial were compared to the surgical arm of the ARTS-I as a historical

control. In order to be sure that the population was comparable to the ARTS-I trial,

patients were stratified by clinical site with the goal of ensuring that at least 1/3 of

patients had three vessel disease. Among the 607 patients included in ARTS-II

study, 159 of them had diabetes. Investigators compared DES with BMS and also

compared DES with CABG. At three year follow-up, there was no significant

difference in the main outcome (MACCE) between those who received DES and

those who received CABG. However at five year follow-up, the rate of MACCE was

lower in CABG than in DES (23.4% vs 40.5%: p< 0.001). Thus, CABG appeared safer

at five year follow up. Caution should be used in drawing conclusions, since this

was a subgroup analysis using a group of historical controls.

2. Synergy 2. Synergy 2. Synergy 2. Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX)between PCI with Taxus and Cardiac Surgery (SYNTAX)between PCI with Taxus and Cardiac Surgery (SYNTAX)between PCI with Taxus and Cardiac Surgery (SYNTAX)

SYNTAX was a large randomized controlled trial including 1,800 patients and

conducted at 85 sites.26 The study was designed to compare CABG and DES

(paclitaxel) in patients with three vessel or left main coronary disease. The main

outcome was major adverse cardiac and cerebrovascular events (MACCE). Overall,

rates of MACCE were significantly higher in those who received DES than those who

received CABG. This study was designed as a non-inferiority trial but because of

the significant difference in MACCE between groups, the criteria for noninferiority

were not met.

A subgroup analysis of SYNTAX in patients with diabetes was prespecified. A

total of 452 of the trial participants had diabetes. At one year follow-up there was

no difference between the two groups, but at three year follow-up diabetics who

received CABG had a 22.9% rate of MACCE and diabetics who received DES had a

rate of 37.0% (p = 002).29,31 Thus, in this prespecified subgroup analysis, the rate of

adverse events was lower in those who received CABG than in those who received

DES.

3. 3. 3. 3. Coronary Artery Revascularization in Diabetes Study (CARDia)Coronary Artery Revascularization in Diabetes Study (CARDia)Coronary Artery Revascularization in Diabetes Study (CARDia)Coronary Artery Revascularization in Diabetes Study (CARDia)

The CARDia study was the first randomized controlled trial that specifically

focused on the role of PCI with DES and CABG in diabetic patients with multi-vessel

coronary artery disease.28 This was a non-inferiority trial designed to show whether

or not PCI was or was not non-inferior to CABG. Patients were included if they had

diabetes and either multi-vessel coronary artery disease or complex single vessel

disease (ostial or proximal left anterior descending artery disease). Patients had to

be eligible to receive either PCI or CABG in order to be included. Patients were

randomized to either receive PCI or CABG. The trial started out with patients

receiving BMS, but when DES became available, patients received DES. The primary

endpoint was a composite end point assessed at one year after randomization. The

composite end point included death, MI and stroke. A major secondary endpoint

was repeat revascularization at one-year follow-up.

Among those who received stents, 69% received DES and 31% received BMS.

At one-year follow-up there was a trend toward a reduction in the composite end

point in those who received CABG compared with PCI, but this reduction was not

statistically significant. (10.5% CABG vs 13.0% PCI: HR 1.25: 95% C.I. 0.75-2.09: p =

0.39) The rate of all cause mortality was 3.2% in each group. The combined

endpoint of MACCE was 11.3% in the CABG group and 19.3% in the PCI group (HR

1.77: 95% C.I. 1.11-2.82: p = 0.02). When the patients who received CABG were

compared with the subset of patients who received DES, there were still no

statistically significant differences.

These results at one year did not show that PCI was non-inferior to CABG.

Although there was a trend toward a reduction in the composite outcome among

those treated with CABG compared with those treated with PCI, this was not

statistically significant. This could be because there truly is no difference or could

be because of inadequate power of the trial to detect a true difference. Regardless,

the CARDia study alone did not answer the question of whether PCI or CABG

should be preferred in patients with diabetes.

4. Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal 4. Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal 4. Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal 4. Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal

MaMaMaManagement of Multinagement of Multinagement of Multinagement of Multi----Vessel Disease Study (FREEDOM)Vessel Disease Study (FREEDOM)Vessel Disease Study (FREEDOM)Vessel Disease Study (FREEDOM)

The major study that addresses the role of PCI plus stenting vs CABG in

diabetics is the FREEDOM study. The FREEDOM study was a large multi-center RCT

that compared DES to CABG in patients with multi-vessel coronary artery disease.32

A total of 1,900 diabetic patients at a total of 140 centers around the world were

randomized to receive PCI with DES or CABG. Patients were included if they had

Type I or Type 2 diabetes and had angiographically confirmed multi-vessel

coronary artery disease with stenosis of more than 70% in two or more major

epicardial vessels involving at least two separate coronary artery territories and

without left main disease. Among those receiving DES, sirolimus-eluting and

paclitaxel-eluting stents were most commonly used. A newer generation of drug

eluting stent could be used as long as it was FDA approved. Abciximab was

recommended for patients undergoing PCI. Dual antiplatelet therapy with aspirin

and clopidrogel was recommended for at least 12 months after stent implantation.

For CABG surgery, arterial revascularization was encouraged. Risk factor

modification was encouraged in all patients, and recommended targets were set.

These included a goal low density lipoprotein (LDL) of <70 mg/deciliter, a goal

blood pressure of <130/80 and a goal glycosylated hemoglobin of <7%.

The primary study outcome was a composite of all cause mortality, nonfatal

MI and nonfatal stroke. Secondary outcomes included rate of MACCE at 30 days

and 12 months after the procedure (including some components of the primary

outcome and repeat revascularization).

Mean patient age was 63.1 years, 29% were women and 83% had triple

vessel disease. The primary composite outcome was more common at five year

follow-up in the PCI group (26.6% PCI vs 18.7% CABG: p =0.005). When outcomes

were analyzed individually, at five year follow-up, MI was lower in CABG group

(6.0% vs 13.9%: p < 0.001) and all cause mortality was also lower in the CABG group

(10.9% vs 16.3%: p = 0.049). Stroke at five year follow up was higher in the CABG

group than in the PCI group (5.2% vs 2.4%: p = 0.03).

This large trial with adequate power has answered the question of whether

CABG or PCI with DES is superior in patients with diabetes. This study has clearly

shown that for patients with diabetes and multi-vessel coronary artery disease,

CABG is superior to PCI. It significantly reduced the rate of the composite endpoint

(mortality, MI and stroke). In addition, overall mortality and MI were both reduced,

although there was a small increased risk of stroke in those who received CABG.

Thus, this study clearly shows that in diabetics, PCI using the current

technology of DES is inferior to CABG. PCI does not show an improvement in

clinical outcomes compared with the established alternative of CABG in diabetic

patients with multi-vessel disease who are undergoing revascularization.

Summary Summary Summary Summary

In summary, the current standard for PCI procedure uses DES. Among the

trials comparing PCI with DES to CABG, two were subgroup analyses - one showed

no difference between the interventions and one showed worse outcome with PCI.

Two trials evaluated PCI with DES vs CABG exclusively in diabetics - one was small

and underpowered. The large FREEDOM trial included 1,900 diabetics and

definitively showed a significant reduction in mortality and myocardial infarction

with CABG compared with PCI, although was associated with a small increased risk

of stroke. This study has shown us that CABG is superior to PCI for diabetics with

multi-vessel disease requiring revascularization. PCI when compared with the

established alternative of CABG does not result in an improvement in health

outcomes.

TA Criterion 4 is TA Criterion 4 is TA Criterion 4 is TA Criterion 4 is not metnot metnot metnot met for PCI as an alternative to CABGfor PCI as an alternative to CABGfor PCI as an alternative to CABGfor PCI as an alternative to CABG for diabetics with multifor diabetics with multifor diabetics with multifor diabetics with multi----

vessel disease. vessel disease. vessel disease. vessel disease.

TA Criterion 5:TA Criterion 5:TA Criterion 5:TA Criterion 5: The improvement must be attainable outside of the The improvement must be attainable outside of the The improvement must be attainable outside of the The improvement must be attainable outside of the

investigational investigational investigational investigational setting.setting.setting.setting.

Since the improvement has not been shown in the investigational setting, an

improvement cannot be obtained outside of the investigational setting.

TA Criterion 5 is notTA Criterion 5 is notTA Criterion 5 is notTA Criterion 5 is not met.met.met.met.

CONCLUSIONCONCLUSIONCONCLUSIONCONCLUSION

In summary, PCI is being compared to CABG in diabetics with multi-vessel

disease. Many studies have compared PCI and CABG in patients with coronary

disease. The majority of the early studies conducted subgroup analyses of

diabetics, most suggesting at least a trend toward improvement with CABG. In

addition, PCI technology has progressed from balloon angioplasty to BMS and now

to the current standardly used technology of DES. However, even using the

currently used PCI technology of DES, PCI compared with CABG does not lead to an

improvement in health outcomes.

DRAFT DRAFT DRAFT DRAFT RECRECRECRECOMMENDATIONOMMENDATIONOMMENDATIONOMMENDATION

It is recommended that PCI as an alternative to CABG in patients with

diabetes mellitus does not meet CTAF criteria 4 or 5 for safety, efficacy and

improvement in health outcomes.

March 6, 2013

RECOMMENDATIONS OF OTHERSRECOMMENDATIONS OF OTHERSRECOMMENDATIONS OF OTHERSRECOMMENDATIONS OF OTHERS

American CollegeAmerican CollegeAmerican CollegeAmerican College of Cardiologyof Cardiologyof Cardiologyof Cardiology

In 2011, the American College of Cardiology released two practice guidelines.

1) In partnership with the American Heart Association (AHA) and the Society for

Cardiovascular Angiography and Interventions (SCAI): 2011 ACCF/AHA/SCAI 2011 ACCF/AHA/SCAI 2011 ACCF/AHA/SCAI 2011 ACCF/AHA/SCAI

guideline foguideline foguideline foguideline for percutaneous coronary artery intervention. A Report of the r percutaneous coronary artery intervention. A Report of the r percutaneous coronary artery intervention. A Report of the r percutaneous coronary artery intervention. A Report of the

American College of Cardiology Foundation/American Heart Association Task American College of Cardiology Foundation/American Heart Association Task American College of Cardiology Foundation/American Heart Association Task American College of Cardiology Foundation/American Heart Association Task

Force on Practice Guidelines and the Society for Cardiovascular Angiography Force on Practice Guidelines and the Society for Cardiovascular Angiography Force on Practice Guidelines and the Society for Cardiovascular Angiography Force on Practice Guidelines and the Society for Cardiovascular Angiography

and Interventions; and Interventions; and Interventions; and Interventions; and

2) In partnership with the American Heart Association: 2011 ACCF/AHA Guideline 2011 ACCF/AHA Guideline 2011 ACCF/AHA Guideline 2011 ACCF/AHA Guideline

for Coronary Artery Bypass Graft Surgery: A Report of the American College of for Coronary Artery Bypass Graft Surgery: A Report of the American College of for Coronary Artery Bypass Graft Surgery: A Report of the American College of for Coronary Artery Bypass Graft Surgery: A Report of the American College of

Cardiology Foundation/American Heart Association Task Force on Practice Cardiology Foundation/American Heart Association Task Force on Practice Cardiology Foundation/American Heart Association Task Force on Practice Cardiology Foundation/American Heart Association Task Force on Practice

GuidelinesGuidelinesGuidelinesGuidelines....

Both sets of guidelines make the following recommendation under sections titled:

Revascularization to Improve Survival: Recommendations; Non-Left Main CAD

Revascularization, Class IIa:

CABG is probably recommended in preference to PCI to improve survival in

patients with multivessel CAD and diabetes mellitus, particularly if a LIMA

graft can be anastomosed to the LAD artery. (Level of Evidence: B)

The ACC was invited to send an opinion on this technology and invited to

send a representative to the meeting.

American Heart American Heart American Heart American Heart Association (AHA)Association (AHA)Association (AHA)Association (AHA)

The AHA was invited to send an opinion on this technology and invited to

send a representative to the meeting. See above for guideline(s).

Society for Cardiovascular Angiography and InterventionsSociety for Cardiovascular Angiography and InterventionsSociety for Cardiovascular Angiography and InterventionsSociety for Cardiovascular Angiography and Interventions (SCAI)(SCAI)(SCAI)(SCAI)

SCAI was invited to send an opinion on this technology and invited to send a

representative to the meeting. See above for guideline(s).

Agency for Healthcare Research and Quality (AHRQ)Agency for Healthcare Research and Quality (AHRQ)Agency for Healthcare Research and Quality (AHRQ)Agency for Healthcare Research and Quality (AHRQ)

AHRQ’s Effective Health Care Program published in 2007 its report:

Comparative Effectiveness of Percutaneous Coronary Interventions and Coronary Comparative Effectiveness of Percutaneous Coronary Interventions and Coronary Comparative Effectiveness of Percutaneous Coronary Interventions and Coronary Comparative Effectiveness of Percutaneous Coronary Interventions and Coronary

Artery Bypass Grafting for Coronary Artery Disease.Artery Bypass Grafting for Coronary Artery Disease.Artery Bypass Grafting for Coronary Artery Disease.Artery Bypass Grafting for Coronary Artery Disease. One of the key questions in the

report was to determine the evidence of comparative effectiveness of PCI and

CABG based on coronary diseases risk factors, diabetes or other comorbid disease.

The report notes the following:

“…six RCTs reporting survival of diabetic patients at one and five years. One

RCT - Bypass Angioplasty Revascularization Investigation (BARI) trial - found

significantly better survival for diabetic patients assigned to CABG while

none of the other five trials found significant differences in survival between

diabetic patients with PCI vs. CABG. However, the pooled data from all the

trials showed no significant difference in survival after PCI or CABG.”

Blue Cross Blue Shield Association (BCBSA)Blue Cross Blue Shield Association (BCBSA)Blue Cross Blue Shield Association (BCBSA)Blue Cross Blue Shield Association (BCBSA)

No assessments on this technology were found on the BCBSA TEC website.

Canadian Agency for Drugs and Technologies in Health (CADTH)Canadian Agency for Drugs and Technologies in Health (CADTH)Canadian Agency for Drugs and Technologies in Health (CADTH)Canadian Agency for Drugs and Technologies in Health (CADTH)

On October, 2012, CADTH issued its Rapid Response Report: Rapid Response Report: Rapid Response Report: Rapid Response Report: Drug Eluting Drug Eluting Drug Eluting Drug Eluting

Stents for Patients with Diabetes and Coronary Artery Disease: A Review of the Stents for Patients with Diabetes and Coronary Artery Disease: A Review of the Stents for Patients with Diabetes and Coronary Artery Disease: A Review of the Stents for Patients with Diabetes and Coronary Artery Disease: A Review of the

Clinical EvidenceClinical EvidenceClinical EvidenceClinical Evidence and Guidelinesand Guidelinesand Guidelinesand Guidelines to determine the clinical effectiveness and drug

safety of drug eluting stents in adults with both diabetes and coronary artery

disease and to find any evidence guidelines on this topic. Based on its findings,

CADTH wrote the following:

“In adults with diabetes and coronary artery disease, findings from both

randomized and non- randomized controlled trials showed consistently that

the clinical effectiveness, as measured by the need for a repeat

revascularization of the target vessel, is the best with CABG, followed by DES

(drug eluting stents), then BMS (bare metal stents). Findings on safety

outcomes such as risk of death and myocardial infarction are similar

between DES and BMS up to 2.5 years follow-up and in favour of DES with

longer follow-up times. Findings on comparisons between DES and CABG

are inconsistent on safety outcomes. There was no evidence found on

guidelines for the use of DES in adult patients with both diabetes and

coronary artery disease.”

National Institute for Health and Clinical Excellence (NICE)National Institute for Health and Clinical Excellence (NICE)National Institute for Health and Clinical Excellence (NICE)National Institute for Health and Clinical Excellence (NICE)

NICE clinical guideline 126: Management of Stable AnginaNICE clinical guideline 126: Management of Stable AnginaNICE clinical guideline 126: Management of Stable AnginaNICE clinical guideline 126: Management of Stable Angina (issued on July

2011 and last modified on December 2012) noted the following in the section: Key

Priorities for Implementation:

When either procedure would be appropriate, take into account the

potential survival advantage of CABG over PCI for people with multivessel

disease whose symptoms are not satisfactorily controlled with optimal

medical treatment and who:

• have diabetes or or or or

• are over 65 years orororor

• have anatomically complex three-vessel disease, with or without

involvement of the left main stem.

Centers Centers Centers Centers for Medicare and Medicaid Services (CMS)for Medicare and Medicaid Services (CMS)for Medicare and Medicaid Services (CMS)for Medicare and Medicaid Services (CMS)

National Coverage Determination (NCD) guidelines are available for

Percutaneous Transluminal Angioplasty (PTA) procedures under Section 20.7 in the

Medicare National Determination Coverage Manual. However, there is no NCD for

drug eluting coronary stents themselves used in PTA or PCI.. Local Medicare

carriers have discretion on coverage decisions of coronary stents.

American College of Cardiology (ACS), CA ChapterAmerican College of Cardiology (ACS), CA ChapterAmerican College of Cardiology (ACS), CA ChapterAmerican College of Cardiology (ACS), CA Chapter

ACS – CA Chapter was invited to provide an opinion on this technology and

to send a representative to the CTAF public meeting.

American Association for Thoracic Surgery (AATS)American Association for Thoracic Surgery (AATS)American Association for Thoracic Surgery (AATS)American Association for Thoracic Surgery (AATS)

AATS was invited to provide an opinion on this technology and to send a

representative to the CTAF public meeting.

Society of Thoracic Surgeons (STS)Society of Thoracic Surgeons (STS)Society of Thoracic Surgeons (STS)Society of Thoracic Surgeons (STS)

STS was invited to provide an opinion on this technology and to send a

representative to the CTAF public meeting.

ABBREVIATIONS ABBREVIATIONS ABBREVIATIONS ABBREVIATIONS


AV: Arterio Venous



BMS: Bare Metal Stents




CARdia: Coronary Artery Revascularization in Diabetes

CASS: Coronary Artery Surgery Study

CVA: Cerebrovascular Accident


CHF: Congestive Heart Failure

C.I.: Confidence Interval

DARE: Database of Abstracts of Reviews of Effects

DES: Drug Eluting Stent(s)


EF: Ejection Fraction

ERACI II: Argentine Randomized Study-coronary Angioplasty with Stenting

Versus coronary Bypass surgery in Multi-Vessel Disease

FDA: Food and Drug Administration

FREEDOM: Future Revascularization Evaluation in Patients with Diabetes Mellitus:

Optimal Management of Multi-Vessel Disease


HR: Hazard Ratio

LAD: Left Anterior Descending

LDL: Low Density Lipoprotein

LV: Left Ventricle or Ventricular

MACCE: Major Adverse Cardiovascular and Cerebrovascular Events (Death,

CVA, MI and repeat revascularization)

MACE: Major Adverse Cardiovascular Events (death, MI and repeat

revascularization)



NHLBI: National Institutes of Health (NIH) Heart, Lung, and Blood Institute

OR: Odds Ratio



RCT: Randomized Controlled Trial

RITA: Randomized Intervention Treatment of Angina

RIVAL: Radial vs Femoral Access for Coronary Angiography and Intervention

in Patients with Acute Coronary Syndromes



ATTACHMENTATTACHMENTATTACHMENTATTACHMENT

Farkouh ME, Domanski M, Sleeper LA, et al. Strategies for multivessel

revascularization in patients with diabetes. N Engl J Med. Dec 20 2012;367(25):2375-

2384

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