Comparative Effectiveness of Percutaneous Coronary Interventions and Coronary Artery Bypass Grafting...

Comparative Effectiveness of Percutaneous Coronary Interventions and Coronary Artery Bypass Grafting for Coronary Artery Disease

January 31, 2006

Dena Bravata, MD, MS and Mark Hlatky, MD

Today’s Talk

Background on the procedures

Methodological issues

Results

Conclusions and next steps

What is coronary artery disease?

A narrowing of the coronary arteries that prevents adequate blood supply to the heart muscle. Usually caused by atherosclerosis, it may progress to the point where the heart muscle is damaged due to lack of blood supply. Such damage may result in infarction, arrhythmias, and heart failure.

PrevalencePrevalence of CAD: 2004 US data: 15.8 million Prevalence of procedures: 2004 US data: 249,000 CABGs and 664,000 PCIs

Coronary Artery Bypass Grafting (CABG)

CABG1967:

– Kolessov: LIMA LAD on a beating heart

– Favaloro: SVG on still heart

Procedural refinements: – arterial rather than vein

grafts – avoid the cardiopulmonary

bypass machine– smaller thoracotomy

incision rather than sternotomy

Percutaneous Coronary Interventions (PCI)

1977: 1st Coronary angioplasty by Gruntzig

Limitation: restenosis

1939-1985

http://circ.ahajournals.org/content/vol93/issue9/images/large/hc0960003004.jpeg

PCI Procedural refinements: Stents

Expandable metal mesh tubes that buttresses the dilated segment, limit restenosis.

Drug eluting stents: further reduce cellular proliferation in response to the injury of dilatation.

Which procedure is best?

Research Questions

What is the effectiveness of PCI compared with CABG in reducing the occurrence of adverse objective outcomes (stroke and death) and improving subjective outcomes (angina and quality of life) in patients with coronary artery disease?

Does the comparative effectiveness of PCI and CABG vary based on demographics, coronary disease risk factors (diabetes), the extent of coronary artery disease, or procedure-specific characteristics?

Max

Max is a 79 yo man with well controlled HTN, hyper-cholesterolemia, afib, and diet controlled-DM who had a vfib arrest in the setting of an MI. His angiogram showed proximal vessel LAD and 3-vessel CAD. He was stabilized, did well, and given the option of PCI or CABG. His UCSF and Stanford doctors reviewed the evidence with him and his family…

Today’s Talk



Results


Overview of Methodologic Approach

Our 1st MMA project: slight procedural differences from other EPC work

Develop a REALLY (no kidding) expert team* Systematic literature search for RCTs Limited/selected searches for observational

studies for generalizability Quality evaluations of primary literature Data extraction: which time points? Data synthesis: which outcome metric?

Literature Search for RCTs

Literature searches– 1/1966 to 8/20061/1966 to 8/2006– Strategy for each source developed through Strategy for each source developed through

clinician/librarian collaborationclinician/librarian collaboration MEDLINE: 1576 citations1576 citations Cochrane: 54 citations54 citations Embase: 65 citations65 citations Additional searches (experts): 7 citations7 citations

Study Selection: RCTs

– Procedures of Interest: Any PCI technology (balloon angioplasty with or without stents) vs. any CABG technology (traditional on-pump or off-pump bypass)

– Outcomes of Interest: The short- and long-term objective outcomes (survival, event-free survival, non-fatal MIs, CHF, stroke, infections, other procedural complications, costs) and subjective outcomes (QOL, angina)

Synthesizing Survival Curves

DigitizeIt Software

BARI

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Data Synthesis

Goal: To evaluate the comparative effectiveness of PCI and CABG at 1-, 6-, 12-, 24-, 36-, and 60-months post-procedure.

We computed 2 summary effects for each outcome at each time intervals using random effects models

– Measure of absolute risk: summary risk differences– Measure of relative risk: summary odds ratios

Selecting Outcome Metrics

PCI

CABG

Dead Alive

PPCI

PCABG 1-PCABG

1-PPCI

Absolute Risk: Interpretable; Stable even when rates are low

Risk Difference = PPCI – PCABG

Variance = (PPCI)(1-PPCI)/NPCI + (PCABG)(1-PCABG)/NCABG

Relative Risk: Can be unstable when rates are low

Odds Ratio = (PPCI )(1-PPCI)/(PCABG)(1-PCABG)

Variance = 1/(PPCI)(1-PPCI)NPCI + 1/(PCABG)(1-PCABG)NCABG

Observational Studies

Goals: Assess the generalizability of the RCT results; address questions left unanswered by the RCTs.

Sources: Expert advisors; literature search for RCTs; additional, limited MEDLINE and internet searches.

Inclusion criteria: – Large (at least 1000 patients in each arm)– Provide sufficient information about the patient

populations and procedures performed to draw comparisons with the RCT populations.

Today’s Talk



Results


General Description of the Included Studies

RCTs:113 included articles, 22 unique RCTs 113 included articles, 22 unique RCTs ((See handout)

9,640 patients: 4969 PCI, 4894 CABG

Most were conducted in Europe/UK Only 3 trials performed in the US

High quality trials except for Seoul (?randomized)

Observational Studies:94 included articles, 10 registries94 included articles, 10 registriesGenerally similar populations to the RCT populations (fewer women, more unstable angina patients than in the RCTs)

RCTs: Patient CharacteristicsAge: Mean 61 years

Gender: 27% women

Race/Ethnicity: Overwhelmingly European ancestry

Typical CAD patients who can receive either intervention (not entire CAD spectrum):

20% diabetes, 50% hypertension,50% chol

Among multi-vessel disease (MVD) studies: most patients had 2-vessel rather than 3-vessel disease

40% prior MI, low rates of CHF, good LV function

Very few patients with left main or SVD

Results: Overall SurvivalMyoprotect and AWESOME enrolled much more acutely ill populations than the other 20 trials.

PCI Recipients

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PCI Procedures

Use of stents and adjunctive therapy with aspirin, clopidogrel/ticlopidine, and heparin was common in the newer stent, but not in the balloon trials.

1987-1993: balloonBARICABRI EASTERACIGABILausanneMASSRITAToulouse

1998-2003: stentsAMISTARTSAWESOMEERACI IIGroningenLeipzigMASS II

MyoprotectPolandOctostentSeoulSIMASoS

CABG Procedures

LIMA was frequently employed, especially in more recent trials.

Few CABGs were performed off-pump, although a few studies used minimally invasive direct coronary artery bypass (MIDCAB) incisions and beating heart operations in patients with single-vessel LAD disease.

In patients with MVD, surgeons generally bypassed more vessels than angioplasty operators dilated.

Comparative Effectiveness Results

Procedural outcomesLong-term outcomesSubgroup analyses

Procedural Survival (Risk Difference)Study name Outcome Time point Statistics for each study Survival / Total Risk difference and 95% CI

Risk Lower Upper difference limit limit p-Value PCI CABG

AMIST Survival 1 month 0.000 -0.038 0.038 1.000 50 / 50 50 / 50 All PatientsARTS Survival 1 month -0.002 -0.015 0.012 0.794 591 / 600 597 / 605 All PatientsAWESOME Survival 1 month 0.020 -0.016 0.056 0.275 215 / 222 220 / 232 All PatientsBARI Survival 1 month 0.002 -0.008 0.012 0.666 905 / 915 902 / 914 All PatientsCABRI Survival 1 month -0.001 -0.015 0.012 0.855 534 / 541 507 / 513 All PatientsEAST Survival 1 month 0.000 -0.020 0.020 1.000 196 / 198 192 / 194 All PatientsERACI Survival 1 month 0.031 -0.028 0.090 0.307 62 / 63 61 / 64 All PatientsERACI II Survival 1 month 0.049 0.016 0.082 0.004 223 / 225 212 / 225 All PatientsGABI Survival 1 month 0.029 -0.007 0.064 0.116 179 / 182 169 / 177 All PatientsGroningen Survival 1 month 0.039 -0.025 0.103 0.229 51 / 51 49 / 51 All PatientsLausanne Survival 1 month 0.000 -0.029 0.029 1.000 68 / 68 66 / 66 All PatientsLeipzig Survival 1 month 0.018 -0.012 0.048 0.239 110 / 110 108 / 110 All PatientsMASS Survival 1 month 0.000 -0.027 0.027 1.000 72 / 72 70 / 70 All PatientsMASS-II Survival 1 month 0.000 -0.030 0.030 0.987 200 / 205 198 / 203 All PatientsMyoprotect Survival 1 month 0.008 -0.162 0.178 0.927 21 / 23 19 / 21 All PatientsOctostent Survival 1 month 0.014 -0.010 0.038 0.244 138 / 138 140 / 142 All PatientsPoland Survival 1 month 0.000 -0.038 0.038 1.000 50 / 50 50 / 50 All PatientsRITA Survival 1 month 0.004 -0.008 0.016 0.507 506 / 510 495 / 501 All PatientsSeoul Survival 1 month -0.003 -0.039 0.034 0.891 117 / 119 69 / 70 All PatientsSIMA Survival 1 month -0.016 -0.059 0.028 0.474 62 / 63 60 / 60 All PatientsSoS* Survival 1 month -0.006 -0.014 0.002 0.150 484 / 488 499 / 500 All PatientsToulouse Survival 1 month 0.000 -0.036 0.036 1.000 75 / 76 75 / 76 All Patients

0.001 -0.003 0.006 0.508 4910 / 4969 4809 / 4894

-0.25 -0.13 0.00 0.13 0.25

Favors CABG Favors PCI

Heterogeneity Statistics: Q-value 20.3, P-value 0.5; I-squared 0.000.

Procedural mortality rare for both procedures; no significant difference between them.

Study name Outcome Time point Statistics for each study Survival / Total Odds ratio and 95% CI

Odds Lower Upper ratio limit limit p-Value PCI CABG

ARTS Survival 1 month 0.880 0.337 2.296 0.794 591 / 600 597 / 605 All PatientsAWESOME Survival 1 month 1.702 0.644 4.495 0.283 215 / 222 220 / 232 All PatientsBARI Survival 1 month 1.204 0.518 2.801 0.666 905 / 915 902 / 914 All PatientsCABRI Survival 1 month 0.903 0.301 2.704 0.855 534 / 541 507 / 513 All PatientsEAST Survival 1 month 1.000 0.137 7.315 1.000 196 / 198 192 / 194 All PatientsERACI Survival 1 month 3.166 0.304 33.005 0.335 62 / 63 61 / 64 All PatientsERACI II Survival 1 month 6.837 1.525 30.659 0.012 223 / 225 212 / 225 All PatientsGABI Survival 1 month 2.824 0.737 10.824 0.130 179 / 182 169 / 177 All PatientsGroningen Survival 1 month 5.202 0.244 111.093 0.291 51 / 51 49 / 51 All PatientsLeipzig Survival 1 month 5.092 0.242 107.297 0.295 110 / 110 108 / 110 All PatientsMASS-II Survival 1 month 1.010 0.288 3.544 0.987 200 / 205 198 / 203 All PatientsMyoprotect Survival 1 month 1.102 0.141 8.615 0.927 21 / 23 19 / 21 All PatientsOctostent Survival 1 month 4.929 0.234 103.598 0.305 138 / 138 140 / 142 All PatientsRITA Survival 1 month 1.533 0.430 5.467 0.510 506 / 510 495 / 501 All PatientsSeoul Survival 1 month 0.848 0.075 9.523 0.894 117 / 119 69 / 70 All PatientsSIMA Survival 1 month 0.344 0.014 8.619 0.516 62 / 63 60 / 60 All PatientsSoS* Survival 1 month 0.185 0.014 2.398 0.197 484 / 488 499 / 500 All PatientsToulouse Survival 1 month 1.000 0.061 16.285 1.000 75 / 76 75 / 76 All Patients

1.386 0.977 1.966 0.067 4670 / 47294573 / 4658

0.01 0.1 1 10 100


Procedural Survival (Odds Ratio)

There is no difference in outcome between absolute and relative risk metrics.

1990-1993 (Balloon-era)

RD: 0.003

1998-2003 (Stent-era) RD: 0.005

Procedural Survival

No difference in procedural survival between balloon vs. CABG and stent vs. CABG. Also no comparative

difference between SVD and MVD trials.

Study name Outcome Time point Statistics for each study Survival / Total Risk difference and 95% CI


ARTS Stroke 1 month 0.004 -0.011 0.019 0.611 590 / 600 592 / 605 All PatientsAWESOME Stroke 1 month 0.004 -0.015 0.023 0.682 220 / 222 229 / 232 All PatientsBARI Stroke 1 month 0.006 -0.000 0.012 0.069 913 / 915 907 / 914 All PatientsEAST Stroke 1 month 0.010 -0.010 0.030 0.320 197 / 198 191 / 194 All PatientsGABI Stroke 1 month 0.011 -0.008 0.030 0.249 182 / 182 175 / 177 All PatientsGroningen Stroke 1 month -0.020 -0.073 0.033 0.459 50 / 51 51 / 51 All PatientsLausanne Stroke 1 month 0.009 -0.027 0.045 0.627 68 / 68 65 / 66 All PatientsMASS Stroke 1 month 0.000 -0.027 0.027 1.000 72 / 72 70 / 70 All PatientsOctostent Stroke 1 month 0.000 -0.014 0.014 1.000 138 / 138 142 / 142 All PatientsRITA Stroke 1 month 0.008 -0.002 0.018 0.100 509 / 510 496 / 501 All PatientsSeoul Stroke 1 month 0.014 -0.021 0.049 0.435 119 / 119 69 / 70 All PatientsSIMA Stroke 1 month -0.016 -0.060 0.028 0.471 62 / 63 60 / 60 All PatientsERACI-II Stroke 1 month 0.009 -0.006 0.024 0.240 225 / 225 223 / 225 All PatientsMASS II Stroke 1 month 0.020 -0.007 0.047 0.149 203 / 205 197 / 203 All Patients

0.006 0.002 0.010 0.002 3548 / 3568 3467 / 3510

-0.25 -0.13 0.00 0.13 0.25


Freedom from Procedural Stroke

Heterogeneity Statistics: Q-value 4.9, P-value 0.98; I-squared 0

Odds Ratio Analysis: 1.93 (95%CI: 1.14, 3.29, p=0.02)

Procedural strokes (reported by 14 trials) were significantly higher after CABG than after PCI (1.2% vs. 0.6%). The risk difference 0.6% (95% CI: +0.2% to +1%, p=0.002) and odds ratio 1.9 (95% CI: 1.14, 3.29, p=0.015) were statistically homogeneous.

Freedom from Procedural MIStudy name Outcome Time point Statistics for each study Survival / Total Risk difference and 95% CI


AMIST MI 1 month 0.000 -0.038 0.038 1.000 50 / 50 50 / 50 All PatientsARTS MI 1 month -0.002 -0.021 0.018 0.847 581 / 600 587 / 605 All PatientsBARI MI 1 month 0.024 0.008 0.040 0.004 896 / 915 873 / 914 All PatientsEAST MI 1 month 0.073 0.024 0.122 0.004 192 / 198 174 / 194 All PatientsERACI MI 1 month -0.001 -0.085 0.083 0.981 59 / 63 60 / 64 All PatientsERACI II MI 1 month -0.033 -0.081 0.015 0.179 205 / 225 212 / 225 All PatientsGABI MI 1 month 0.051 0.008 0.095 0.022 178 / 182 164 / 177 All PatientsGroningen MI 1 month -0.078 -0.168 0.012 0.088 46 / 51 50 / 51 All PatientsLausanne MI 1 month -0.014 -0.064 0.036 0.575 66 / 68 65 / 66 All PatientsLeipzig MI 1 month 0.018 -0.025 0.061 0.407 108 / 110 106 / 110 All PatientsMASS MI 1 month -0.013 -0.061 0.034 0.574 70 / 72 69 / 70 All PatientsMASS-II MI 1 month 0.000 -0.019 0.019 0.992 203 / 205 201 / 203 All PatientsOctostent MI 1 month 0.013 -0.025 0.052 0.497 135 / 138 137 / 142 All PatientsPoland MI 1 month -0.020 -0.074 0.034 0.465 49 / 50 50 / 50 All PatientsRITA MI 1 month -0.011 -0.032 0.010 0.287 492 / 510 489 / 501 All PatientsSeoul MI 1 month -0.005 -0.056 0.046 0.845 115 / 119 68 / 70 All PatientsSIMA MI 1 month -0.014 -0.084 0.055 0.687 60 / 63 58 / 60 All PatientsSoS MI 1 month -0.023 -0.043 -0.003 0.027 469 / 488 492 / 500 All PatientsToulouse MI 1 month 0.013 -0.053 0.080 0.699 73 / 76 72 / 76 All Patients

0.001 -0.010 0.013 0.808 4047 / 4183 3977 / 4128

-0.25 -0.13 0.00 0.13 0.25


Heterogeneity Statistics: Q-value 35, P-value 0.009; I-squared 49

Procedural MIs were slightly higher among CABG recipients but not statistically significantly. Risk difference 0.1% (95% CI: -1.0% to +1.3%) and odds ratio 1.06 (95% CI: 0.72, 1.6). There was significant heterogeneity in this outcome.

Generalizability of the Procedural Outcomes: Observational Studies

Procedural risk in RCTs was lower overall than in the large registries. – Society of Thoracic Surgeons: operative

mortality 3.2%2.2% (19952005) despite patients of higher risk profiles

– Hospital Corp. of America (1999-2002): procedural mortality was 1.25% for PCI vs 2.63% for CABG and that mortality fell for both over the interval studied.

Potential explanation: rigorous RCT selection of patient, institutions, and operators

Long Term Survival

Overall survival across all randomized trials did not differ significantly between CABG and PCI between one and five years of follow-up: Risk difference at each time point was less than 1%. (See handout.)

Risk difference between PCI and CABG was smaller in the more recent stent trials. Caveat: recent trials included more patients with single-vessel LAD disease and had shorter follow-up.

Long-term Survival 11 RCTsStudy name Outcome Time point Risk difference and 95% CI

ARTS Survival 12 months All PatientsAWESOME Survival 12 months All PatientsBARI* Survival 12 months All PatientsEAST Survival 12 months All PatientsERACI II Survival 12 months All PatientsGABI Survival 12 months All PatientsLeipzig* Survival 12 months All PatientsMASS Survival 12 months All PatientsMASS-II Survival 12 months All PatientsRITA* Survival 12 months All PatientsToulouse* Survival 12 months All Patients

-0.25 -0.13 0.00 0.13 0.25


Study name Outcome Time point Risk difference and 95% CI

ARTS Survival 60 months All PatientsAWESOME Survival 60 months All PatientsBARI Survival 60 months All PatientsEAST Survival 60 months All PatientsERACI II Survival 60 months All PatientsGABI* Survival 60 months All PatientsLeipzig Survival 60 months All PatientsMASS Survival 60 months All PatientsMASS-II Survival 60 months All PatientsRITA Survival 60 months All PatientsToulouse Survival 60 months All Patients

-0.25 -0.13 0.00 0.13 0.25


At 5-Years:

RD: -0.006 (95%CI: -0.024, 0.11)

OR: 0.9 (95%CI: 0.78, 1.14)

At 1-Year:

RD: -0.001 (95%CI: -0.009, 0.11)

OR: 1.1 (95%CI: 0.86, 1.49)

There is no difference in survival from the 11 RCTs that reported both 1 and 5 year survival data.

Single-vessel vs. Multi-vessel Disease

7 trials proximal LAD, 15 trials MVD7 trials proximal LAD, 15 trials MVD

No statistically significant differences in comparative survival at any time post-procedure between SVD and MVD trials; however:– SVD-LAD trials: survival was 1% greater for

CABG recipients (95%CI: -5% to +2%) among balloon trials and was 0.1% greater for PCI recipients (95%CI: -4% to +4%) among stent trials.

– MVD trials: survival 0.6% greater for CABG recipients (95%CI: -1.5% to +0.4%) for balloon trials but was 1.4% greater for PCI recipients (95% CI: -1% to

+3.8%) for the stent trials.

Angina Relief

Angina relief was more complete after CABG than after PCI at all intervals post-procedure (risk difference ranges from 5% to 8%; odds ratio ranged from 0.5 to 0.66, p<0.0001 at 1-, 3-, and 5-years).

Study name Outcome Time point Statistics for each study Risk difference and 95% CI

Risk Lower Upper difference limit limit p-Value

ARTS Angina 12 months -0.110 -0.155 -0.065 0.000 All Patients

AWESOME Angina 12 months -0.070 -0.163 0.023 0.141 All Patients

CABRI Angina 12 months -0.038 -0.078 0.002 0.065 All PatientsERACI Angina 12 months -0.210 -0.365 -0.055 0.008 All Patients

ERACI II Angina 12 months -0.075 -0.135 -0.015 0.014 All PatientsGABI Angina 12 months -0.030 -0.132 0.072 0.565 All Patients

Lausanne Angina 12 months -0.100 -0.204 0.004 0.060 All Patients

MASS-II Angina 12 months -0.073 -0.171 0.024 0.141 All PatientsOctostent Angina 12 months -0.087 -0.176 0.002 0.054 All Patients

SIMA Angina 12 months -0.040 -0.130 0.050 0.382 All Patients

SoS Angina 12 months -0.141 -0.197 -0.084 0.000 All Patients-0.082 -0.102 -0.061 0.000

-0.25 -0.13 0.00 0.13 0.25


Heterogeneity statistics: Q-value 15.0, p-value 0.13, I-squared 33.3.

Freedom From Repeat RevascularizationStudy name Outcome Time point Statistics for each study Risk difference and 95% CI


ARTS Revasc 12 months -0.181 -0.221 -0.140 0.000 All Patients

CABRI Revasc 12 months -0.337 -0.381 -0.292 0.000 All Patients

EAST Revasc 12 months -0.410 -0.506 -0.314 0.000 All PatientsERACI Revasc 12 months -0.290 -0.419 -0.160 0.000 All Patients

ERACI II Revasc 12 months -0.120 -0.177 -0.063 0.000 All PatientsGABI Revasc 12 months -0.530 -0.615 -0.444 0.000 All Patients

MASS-II Revasc 12 months -0.124 -0.172 -0.075 0.000 All Patients

Myoprotect Revasc 12 months -0.281 -0.506 -0.055 0.015 All PatientsOctostent Revasc 12 months -0.087 -0.150 -0.025 0.006 All Patients

Poland Revasc 12 months -0.185 -0.322 -0.048 0.008 All Patients

SoS Revasc 12 months -0.136 -0.175 -0.098 0.000 All Patients-0.239 -0.314 -0.163 0.000

-0.50 -0.25 0.00 0.25 0.50


1-yr: PCI recipients required 24% more repeat procedures than CABG recipients (p <0.0001). 5-yr: This difference climbed to 33% (p<0.0001).Statistically heterogeneous outcome.

Freedom from Repeat Revascularization

At 5-yrs the gap between PCI and CABG narrows somewhat among the stent trials compared to the balloon trials.



BARI Revasc 60 months -0.380 -0.418 -0.342 0.000 All Patients

EAST Revasc 60 months -0.451 -0.581 -0.321 0.000 All Patients

Lausanne Revasc 60 months -0.290 -0.427 -0.153 0.000 All Patients

MASS Revasc 60 months -0.296 -0.403 -0.188 0.000 All Patients

RITA Revasc 60 months -0.435 -0.488 -0.382 0.000 All Patients

Toulouse Revasc 60 months -0.200 -0.386 -0.014 0.035 All Patients

-0.367 -0.423 -0.310 0.000

-0.50 -0.25 0.00 0.25 0.50




ARTS Revasc 60 months -0.373 -0.429 -0.316 0.000 All Patients

ERACI II Revasc 60 months -0.209 -0.287 -0.131 0.000 All Patients

Leipzig Revasc 60 months -0.224 -0.332 -0.117 0.000 All Patients

-0.273 -0.391 -0.156 0.000

-0.50 -0.25 0.00 0.25 0.50


Balloon Angioplasty

Bare Metal Stents

Post-procedure MI

10 studies reported MIs during follow-up Between 1 and 5 yrs post-procedure, the MI

rate increased among all patients, but at a somewhat higher rate for PCI recipients.

However, the risk differences were small (less than 1%) (odds ratio ranged from 0.87 to 0.92) and did not achieve statistical significance.

Quality of Life QOL was collected by 11 trials.

In general, QOL scores were higher among CABG patients over 1-3 yrs of follow-up; however, many trials reported no significant differences between PCI and CABG recipients.

QOL was strongly correlated with angina relief. Thus, improvements in QOL were consistent with the greater relief of angina by CABG over the first few years of follow-up.

Costs

Evaluated in 10 trials.

Considerable heterogeneity in methods of cost determination and health care systems.

9 of 10 trials, PCI patients had much lower initial costs than CABG patients, but the difference in costs between procedures narrowed over time.

In medium to long-term follow-up, PCI-assigned patients had only modestly lower costs (about 5%).

Same trends in both balloon and stent trials.

Comparative Cost Data

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Max

Max is a 79 yo man with well controlled HTN, hypercholesterolemia, afib, and diet controlled-DM…knowing about the comparative effectiveness of PCI and CABG by key subgroups would help his decision making…

Issues in Subgroup Analyses

Few studies reported key outcomes for subgroups of interest

Heterogeneity in the outcome metric reported (relative risk reduction vs absolute risk differences)

Lower power statistic: the common test strategy of treatment by interaction p-values

Outcomes in Key Subgroups: AgeAll RCTs

-Very few patients 75 yrs+ were enrolled.

-There were more procedural complications in the older patients, especially stroke.

Outcomes by age evaluated in BARI, AWESOME, and pooled stent trials (ARTS, ERACI-II, MASS-II, SoS)

-BARI: patients aged 65 yrs+ had lower overall survival than younger patients. Risk difference at 7yrs was larger in the older patients (4.7% risk difference; CABG survival 78.7% vs. PCI 74.0%) than younger patients (2.8% risk difference; CABG 88.1% vs. PCI 85.3%).

Outcomes in Key Subgroups: Age

Pooled stent trials: higher 1-yr incidence of death, MI and stroke among patients aged 65 yrs+ compared with younger patients.

Mortality was lower after CABG in the younger patients, and was lower after PCI in the older patients, although there was no statistically significant evidence of a differential treatment effect by age (age by treatment covariate interaction test).

Outcomes in Key Subgroups: GenderGender outcomes reported for BARI, SoS, pooled stent trials

BARI: Women had lower overall survival, but only at 7 years. The risk difference between PCI and CABG was similar in women (3.4% risk difference: 82.6% CABG vs. 79.2% PCI) and in men (3.5% risk difference: 85.1% CABG vs. 81.6% PCI).

SoS trial: Women had lower QOL at baseline, but improved after revascularization. In men, QOL improved more with CABG than with PCI, whereas in women the improvements were similar with CABG and PCI.

Outcomes in Key Subgroups: Diabetes

Patients with diabetes who have CAD have substantially higher morbidity and mortality than patients without diabetes who have CAD.

BARI: At 5 yrs, CABG recipients with DM had better survival (80.5%) than PCI patients with DM (65.5%). By contrast, no difference in survival of patients without diabetes between PCI (91.1%) and CABG (91.1%).

Overall: The summary risk difference at 5 yrs was greater at CABG by only 0.8%, but with very wide confidence limits of -8.3% to 6.6% (odds ratio 0.87; 95%CI: 0.51 to 1.49).

1yr: Survival for Patients by Diabetes StatusStudy name Outcome Time point Statistics for each study Risk difference and 95% CI


ARTS Survival 12 months -0.031 -0.088 0.026 0.281 105 / 112 93 / 96 Diabetes

AWESOME Survival 12 months 0.050 -0.071 0.171 0.417 56 / 65 64 / 79 Diabetes

MASS-II Survival 12 months 0.014 -0.073 0.101 0.749 53 / 56 55 / 59 Diabetes

-0.009 -0.053 0.036 0.703 214 / 233 212 / 234

-0.25 -0.13 0.00 0.13 0.25




ARTS Survival 12 months 0.011 -0.007 0.029 0.230 480 / 488 495 / 509 No Diabetes

MASS-II Survival 12 months -0.005 -0.056 0.045 0.843 141 / 149 137 / 144 No Diabetes

0.009 -0.008 0.026 0.288 621 / 637 632 / 653

-0.25 -0.13 0.00 0.13 0.25


Survival at 1 year for Patients with Diabetes

Survival at 1 year for Patients Without Diabetes



AWESOME Survival 60 months 0.000 -0.144 0.144 1.000 48 / 65 58 / 79 Diabetes

BARI Survival 60 months -0.150 -0.288 -0.012 0.033 45 / 69 75 / 93 Treated Diabetes

EAST Survival 60 months -0.003 -0.166 0.160 0.971 23 / 26 24 / 27 Diabetes

ERACI-II Survival 60 months 0.002 -0.132 0.136 0.977 35 / 39 35 / 39 Diabetes

MASS-II Survival 60 months -0.022 -0.130 0.085 0.684 50 / 56 54 / 59 Diabetes

RITA Survival 60 months 0.173 0.001 0.346 0.049 27 / 29 25 / 33 Diabetes

-0.008 -0.083 0.066 0.823 229 / 284 272 / 330

-0.25 -0.13 0.00 0.13 0.25




BARI Survival 60 months 0.000 -0.037 0.037 1.000 426 / 468 409 / 449 No Diabetes

EAST Survival 60 months -0.039 -0.108 0.030 0.270 130 / 148 137 / 150 No Diabetes

ERACI-II Survival 60 months 0.054 -0.004 0.112 0.069 174 / 186 164 / 186 No Diabetes

MASS-II Survival 60 months 0.037 -0.029 0.104 0.270 138 / 149 128 / 144 No Diabetes

0.013 -0.023 0.049 0.483 868 / 951 838 / 929

-0.25 -0.13 0.00 0.13 0.25


Survival at 5 years for Patients with Diabetes

Survival at 5 years for Patients Without Diabetes

5yr: Survival for Patients by Diabetes Status

Outcomes by Other Risk Factors

There was no evidence that hypertension, tobacco use, renal dysfunction, vascular disease, or obesity increased risk differentially in PCI-assigned and CABG-assigned patients.

Comparative Effectiveness by Extent of CADBARI: Better survival for patients with 2-vsl rather than 3-vsl disease. Risk difference between PCI and CABG at 5-yrs was greater in patients with 3-vsl disease (3.9% risk difference: 84.7% PCI vs. 88.6% CABG) than in patients with 2-vsl disease (2.1% risk difference; 87.6% PCI vs. 89.7% CABG).

Similar trend reported in the EAST trial and the pooled stent-era trials.

By contrast, RITA-I found very little difference in mortality between patients with SVD and MVD (mostly 2-vessel) and similar PCI-CABG risk differences.

Overall, these data suggest that mortality in patients with 3-vsl disease may be reduced somewhat more by CABG than by PCI, and that in SVD there is little mortality difference between PCI and CABG.

Comparative Effectiveness by LV function

RCTs generally required relatively preserved LV function and little CHF. Sick patients excluded.

Only BARI and AWESOME reported outcomes by LV function. Worse survival for low LV function patients than normal LV

function patients. Risk difference favored PCI by 0.4% in the patients with low LV function (CABG 80.7%, PCI 81.1%), whereas it favored CABG by 4% in patients with normal LV function. At 7 yrs, the risk differences favored CABG in both the low (1.3%) and normal (3.6%) LV function groups.

Small and inconsistent differences in the trials limit the conclusions about the comparative efficacy for PCI and CABG by LV function. Ongoing STICH trial is randomizing low EF patients to CABG vs. medical therapy (vs. CABG with ventricular resection).

CABG-specific Factors

“Minimally invasive” surgery (MIDCAB): – small throracotomy incision on a beating heart– Compared with PCI in 7 small trials

SVD proximal LAD PCI with stents as the comparator

These trials showed similar outcomes over a relatively short follow-up period.

There are only a few early trials of balloon angioplasty and standard CABG (Lausanne, MASS-I) in patients with single-vessel disease whose results can be compared with these trials.

In general, the risk differences over one to two years of follow-up are comparable.

Use of Internal Mammary GraftsUse of IMAs ranged from 37% in the early GABI study to 90%+ in the more recent trials.

-0.03

-0.02

-0.01

0.00

0.01

0.02

0.03

0.04

0.05

0.06

30% 40% 50% 60% 70% 80% 90% 100%

Percent Patients Receiving an Internal Mammary Artery Graft

Ris

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iffe

ren

ce i

n S

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at 1

Yea

r

-0.12

-0.10

-0.08

-0.06

-0.04

-0.02

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0.04

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30% 40% 50% 60% 70% 80% 90% 100% 110%

Percent Patients Receiving an Internal Mammary Artery Graft

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k D

iffer

ence

in S

urvi

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t 5 Y

ears

Regression weighted by the sample size: We found that as the % of IMA grafts increases, there is a trend toward the risk difference favoring CABG at 1 yr but not at 5 years (neither association was statistically significant).

1 Year 5 Years

Favors PCI

Favors PCI

Favors CABG

Favors CABG

Prior Procedures Most RCTs excluded patients with prior CABG, but 1

RCT and several registries compared PCI with re-do CABG in patients with a prior CABG.

AWESOME trial (142 with prior CABG): – Procedural mortality was higher in the patients assigned

to re-CABG (8% vs 0%), three-year mortality was only slightly higher (27% vs 22%) and not significantly different.

A similar pattern has been reported by large clinical registry studies from Cleveland, Emory, and Kansas City: procedural mortality was higher for re-do CABG than for PCI, but survival at five to six years of follow-up did not differ significantly.

Volume-Outcome Relationships Randomized trials have not directly tested for

differences in clinical outcomes of PCI and CABG on the basis of process characteristics.

There is considerable evidence from observational studies that procedural risk of both procedures increases significantly in low volume hospitals and with low volume operators. This relationship remains significant for PCI, even as procedural risk has been reduced by the availability of coronary stents and adjunctive therapy.

Max

Based on the best available evidence, Max chose CABG. He chose to have it at a high-volume academic center by a highly experienced surgeon. His surgery was complicated by a stroke and prolonged ICU stay. He was discharged to a skilled nursing facility and died 3 months after his bypass.

Today’s Talk



Results


Conclusions: Survival• Procedural mortality is low for both PCI and CABG

and does not differ significantly (RD: 0.1%).

• Long-term mortality was not substantially different between PCI and CABG up to 5 yrs after the initial procedure (RDs favor CABG over PCI between six months and five years by less than 1%).

• 5-yr survival in the “balloon-era” trials among patients with MVD favored CABG, whereas survival in the “stent-era” trials favored PCI, although this finding was not statistically significant.

Conclusions Freedom from angina and repeat

revascularization strongly favored CABG over PCI.

The overall survival advantage of CABG over PCI among patients with DM was not statistically significant, averaging 0.8% in absolute terms at 5-yrs.

Only a few trials specifically reported outcomes by number of diseased vessels—these suggest that CABG reduces mortality compared with PCI to a greater extent in patients with 3-vsl disease than in patients with 2-vsl disease.

Limitations

• Most RCTs included low prevalence of heart failure and LV function was generally well preserved, limiting our analyses by LF function.

• Many outcomes, including cognitive function, cost, and quality of life outcomes were reported by very few studies.

• Most clinical trials have not reported outcomes in key subgroups.

• Extended follow-up for the most recent trials was not available.

Future Research

Individual patient-level data pooling Clinical trials of drug-eluting stents Explore minimally invasive approaches to CABG

with respect to procedure volume and outcomes Presently, volume-outcomes studies focus

exclusively on mortality. Procedural myocardial infarction, graft patency, relief of angina, and long-term outcomes are also pertinent to decision making and should be explored in relation to volume levels.

Many ThanksCollaborators:Allison GiengerKathy McDonaldVandana SundaramDoug OwensMarco PerezRobin VargheseJohn KapoorReza ArdehaliMoira McKinnonChristopher StaveIngram OlkinOlga SayninaRobert JonesFunding Agencies: AHRQ and VAPhoto Credit: Cynthia Yock

Comparative Effectiveness of Percutaneous Coronary Interventions and Coronary Artery Bypass Grafting...

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