Ten-Year Follow-up Survival of the Medicine,

Angioplasty, or Surgery Study (MASS-II): a

Randomized Controlled Clinical Trial of Therapeutic

Strategies for Multivessel Coronary Artery Disease

Whady Hueb, Neuza Lopes, Bernard J. Gersh, Paulo R. Soares, Expedito E. Ribeiro,

Alexandre C. Pereira, Desiderio Favarato, Antonio Sérgio C. Rocha, Alexandre C.

Hueb and Jose A.F. Ramires

Heart Institute (InCor), University of Sao Paulo, Sao Paulo, Brazil

Competing Interests

• The authors declare no potential competing interest.

• Compared to CABG treatment, PCI or MT is associated with

higher rates of angina and subsequent revascularization, but no

significant differences in mortality or rates of MI have been found.

• Revascularization therapy in stable multivessel coronary artery

disease (CAD) and preserved ventricular function remains

controversial.

BACKGROUND

• To our Knowledge, there is no study that has ever compared

end points among these 3 therapeutic strategies for more than a

5-year follow-up period.

BACKGROUND

• To compare 10-year follow-up survival of the medical treatment,

angioplasty, or surgical strategies among patients with stable

multivessel CAD and preserved ventricular function.

OBJECTIVE

METHODS

RANDOMIZATIONRANDOMIZATION

ANGIOPLASTYANGIOPLASTY(BMS)(BMS)

MEDICAL TREATMENTMEDICAL TREATMENT(alone)(alone)

SURGERYSURGERY(on-pump CABG)(on-pump CABG)

Stable AnginaStable Angina

Multivessel Coronary Artery Disease Multivessel Coronary Artery Disease

Preserved Left Ventricular FunctionPreserved Left Ventricular Function

Surgeon / Interv. Cardiologist / Surgeon / Interv. Cardiologist / ClinicalClinical Cardiologist Team approval Cardiologist Team approval

Recruitment: May 1995 - May 2000 (Heart Institute - InCor)Recruitment: May 1995 - May 2000 (Heart Institute - InCor)

Hueb W., et al. Circulation 2007;115:1082-1089

METHODS

• Primary end-point (composite):

✓ overall mortality,

✓ myocardial infarction,

✓ refractory angina requiring new revascularization

• Ten-Year Follow-Up

• All analysis were done according to intention to treat principle.

• Sample size: power 80% and a two-side level of significance of

0.05% - 191 patients in each group.

• Statistical test: Chi-Square, log-rank test, ANOVA, Tukey

multiple-comparisons test, Cox’s regression and McNemar test.

Statistical Analysis

RESULTS

Hueb W, et al. J Am Coll CardioI 2004; 43:1743-51

1465 patients non-randomized:

SurgerySurgery(n=203)(n=203)

Medical Treatment(n=203)

Angioplasty (n=205)

excluded 18.692 patients:

coronary <30% lesion - 5192

single coronary disease - 3531

previous CABG/PCI - 2908

valvar disease 2701

other - 4361

refused to participate in this trial or

refused the surgical procedure

Database: 20.769 coronary angiographies

Elegible: 2.076 patients(suitable to PCI-CABG)

MASS II MASS II Randomized: 611 patientsRandomized: 611 patients

Demographic ProfileDemographic Profile

Male, (%)Male, (%)

Age (years) mean±SDAge (years) mean±SD

Medical HistoryMedical History

Previous MI, (%)Previous MI, (%)

Smoker, (%)Smoker, (%)

Hypertension, (%)Hypertension, (%)

Diabetes mellitus, (%)Diabetes mellitus, (%)

CCS class 2 or 3, (%)CCS class 2 or 3, (%)

6969

60±960±9

3939

3333

5555

3636

7878

MT(n = 203)

MT(n = 203)

7272

61±61±88

4141

3232

6363

2929

8585

CABG(n = 203)

CABG(n = 203)

6767

60±460±4

5252

2727

6060

2626

7676

PCI(n=205)

PCI(n=205)CharacteristicCharacteristic

0.4120.412

0.9590.959

0.0240.024

0.0130.013

0.2150.215

0.0620.062

0.0060.006

PP

BaselineBaseline Characteristics Characteristics ofof MASSMASS IIII

Clinical Characteristics

- Metabolic Aspects -

MT PCI CABG

(n=203) (n=205) (n=203)

Total Cholesterol (mg/l) 222±39 220±41 214±42 0.063

LDLChol (mg/dl) 148±34 147±36 143±36 0.305

HDL Chol (mg/dl) 37±10 38±10 37±10 0.870

Triglicerides (mg/dl) 178±82 181±73 169±84 0.235

Glucose mg/dl) 139±68 128±60 122±44 0.062

PP

Double-Vessel Disease, (%)

Triple-Vesel Disease, (%)

Proximal LAD disease, (%)

Mean ejection fraction (mean±DP)

Double-Vessel Disease, (%)

Triple-Vesel Disease, (%)

Proximal LAD disease, (%)

Mean ejection fraction (mean±DP)

MT

(n = 203)

MT

(n = 203)

CABG

(n = 203)

CABG

(n = 203)

PCI

(n = 205)

PCI

(n = 205) 41

59

89

0.68±0.07

41

59

89

0.68±0.07

42

58

93

0.67±0.09

42

58

93

0.67±0.09

42

58

93

0.67±0.08

42

58

93

0.67±0.08

PP

Baseline Characteristics - Angiographic Profile -

0.980

0.980

0.312

0.984

0.980

0.980

0.312

0.984

Major Adverse Cardiac Events

- 10-Year Follow-Up -

OutcomesOutcomes

Primary Endpoints, (%)Primary Endpoints, (%)

Overall Mortality, (%)Overall Mortality, (%)

Myocardial Infarction, (%)Myocardial Infarction, (%)

Aditional Intervention, (%)Aditional Intervention, (%)

OutcomesOutcomes

Primary Endpoints, (%)Primary Endpoints, (%)

Overall Mortality, (%)Overall Mortality, (%)

Myocardial Infarction, (%)Myocardial Infarction, (%)

Aditional Intervention, (%)Aditional Intervention, (%)

MT

(n = 203)

MT

(n = 203)

CABG

(n = 203)

CABG

(n = 203)

PCI

(n = 205)

PCI

(n = 205)

59.1

31

20.7

39.4

59.1

31

20.7

39.4

33

25.1

10.3

7.4

33

25.1

10.3

7.4

42.4

24.1

13.3

41.9

42.4

24.1

13.3

41.9

PP

0.089 0.089

<0.001

0.010

0.001

Treatment GroupTreatment GroupTreatment GroupTreatment Group InitialInitialInitialInitial 6 Year6 Year6 Year6 Year3 Year3 Year3 Year3 Year 205205

203203

203203

205205

203203

203203

164164

168168

159159

164164

168168

159159

189189

184184

179179

189189

184184

179179

10 Year10 Year10 Year10 Year156156

152152

140140

156156

152152

140140

PCIPCI

CABGCABG

MTMT

PCIPCI

CABGCABG

MTMT

Overall Mortality-Free Survival

Treatment GroupTreatment GroupTreatment GroupTreatment Group InitialInitialInitialInitial 6 Year6 Year6 Year6 Year3 Year3 Year3 Year3 Year

203203

205205

203203

203203

205205

203203

155155

130130

121121

155155

130130

121121

175175

147147

140140

175175

147147

140140

10 Year10 Year10 Year10 Year

150150

108108

9393

150150

108108

9393

CABGCABG

PCIPCI

MTMT

CABGCABG

PCIPCI

MTMT

Ten-Year Follow-up Event-free Survival

End Point and Treatment Allocation

- CABG vs MT -

End Point and Treatment Allocation

- CABG vs PCI -

End Point and Treatment Allocation

- PCI vs MT -

Multivariate Analysis for Treatment Allocation

Primary end pointsPrimary end points

TreatmentTreatment

PCI/CABGPCI/CABG

MT/CABGMT/CABG

Primary end pointsPrimary end points

TreatmentTreatment

PCI/CABGPCI/CABG

MT/CABGMT/CABG

1.461.46

2.292.29

1.06-2.021.06-2.02

1.69-3.101.69-3.10

1.06-2.021.06-2.02

1.69-3.101.69-3.10

MultivariateMultivariate

HRHR

MultivariateMultivariate

HRHR

<0.001 <0.001

0.0210.021

<0.001<0.001

<0.001 <0.001

0.0210.021

<0.001<0.001

VariablesVariables pppp95% CI95% CI95% CI95% CI

Overall DeathOverall Death

TreatmentTreatment

PCI/CABGPCI/CABG

MT/CABGMT/CABG

Overall DeathOverall Death

TreatmentTreatment

PCI/CABGPCI/CABG

MT/CABGMT/CABG

0.970.97

1.291.29

0.970.97

1.291.29

0.65-1.440.65-1.44

0.89-1.870.89-1.87

0.65-1.440.65-1.44

0.89-1.870.89-1.87

0.241 0.241

0.8780.878

0.1750.175

0.241 0.241

0.8780.878

0.1750.175

Multivariate Analysis for Treatment Allocation

Myocardial Infarction

Treatment

PCI/CABG

MT/CABG

Myocardial Infarction

Treatment

PCI/CABG

MT/CABG

2.90

2.69

2.90

2.69

1.39-6.01

1.30-5.60

1.39-6.01

1.30-5.60

Multivariate

HR

Multivariate

HR

0.012

0.004

0.008

0.012

0.004

0.008

VariablesVariables pp95% CI95% CI

Additional Intervention

Treatment

PCI/CABG

MT/CABG

Additional Intervention

Treatment

PCI/CABG

MT/CABG

3.71

7.58

3.71

7.58

1.82-7.52

3.88-14.81

1.82-7.52

3.88-14.81

<0.001

<0.001

<0.001

<0.001

<0.001

<0.001

CONCLUSION

• All three therapeutic regimens yielded similar and relatively low

rates of overall mortality.

• Compared with CABG, angioplasty was associated with elevated

rate of myocardial infarction and need for revascularization.

• Medical therapy showed significant incidence of myocardial

infarction and high rate of additional revascularization.