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 - PowerPoint PPT Presentation

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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


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Title: 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

Comparative Effectiveness of Percutaneous
Coronary Interventions and Coronary Artery Bypass
Grafting for Coronary Artery DiseaseJanuary 31,
2006Dena Bravata, MD, MS and Mark Hlatky, MD
Todays 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
  • Prevalence 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)
  • 1967
  • 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

Percutaneous Coronary Interventions (PCI)
  • 1977 1st Coronary angioplasty by Gruntzig
  • Limitation restenosis

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
  • 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

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
Todays Talk
  • Background on the procedures
  • Methodological issues
  • Results
  • Conclusions and next steps

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 8/2006
  • Strategy for each source developed through
    clinician/librarian collaboration
  • MEDLINE 1576 citations
  • Cochrane 54 citations
  • Embase 65 citations
  • Additional searches (experts) 7 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
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
  • Measure of relative risk summary odds ratios

Selecting Outcome Metrics
Absolute Risk Interpretable Stable even when
rates are low Risk Difference PPCI
Relative Risk Can be unstable when rates are
low Odds Ratio (PPCI )(1-PPCI)/(PCABG)(1-PCABG)
Variance 1/(PPCI)(1-PPCI)NPCI
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
  • 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.

Todays Talk
  • Background on the procedures
  • Methodological issues
  • Results
  • Conclusions and next steps

General Description of the Included Studies
  • RCTs
  • 113 included articles, 22 unique RCTs (See
  • 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
  • Observational Studies
  • 94 included articles, 10 registries
  • Generally similar populations to the RCT
    populations (fewer women, more unstable angina
    patients than in the RCTs)

RCTs Patient Characteristics
Age 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 Survival
  • Myoprotect and AWESOME enrolled much more acutely
    ill populations than the other 20 trials.

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
1987-1993 balloon BARI CABRI EAST ERACI GABI La
usanne MASS RITA Toulouse
II Groningen Leipzig MASS II
  • Myoprotect
  • Poland
  • Octostent
  • Seoul
  • SIMA
  • SoS

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 outcomes
  • Long-term outcomes
  • Subgroup analyses

Procedural Survival (Risk Difference)
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.
Procedural Survival (Odds Ratio)
There is no difference in outcome between
absolute and relative risk metrics.

Procedural Survival
1990-1993 (Balloon-era) RD 0.003
1998-2003 (Stent-era) RD 0.005
No difference in procedural survival between
balloon vs. CABG and stent vs. CABG. Also no
comparative difference between SVD and MVD trials.
Freedom from Procedural Stroke
Heterogeneity Statistics Q-value 4.9, P-value
0.98 I-squared 0 Odds Ratio Analysis 1.93
(95CI 1.14, 3.29, p0.02)
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, p0.002) and odds ratio 1.9
(95 CI 1.14, 3.29, p0.015) were statistically
Freedom from Procedural MI
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 (1995?2005) 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
  • Potential explanation rigorous RCT selection of
    patient, institutions, and operators

Comparative Effectiveness Results
  • Procedural outcomes
  • Long-term outcomes
  • Subgroup analyses

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 RCTs
At 1-Year RD -0.001 (95CI -0.009, 0.11) OR
1.1 (95CI 0.86, 1.49)
  • At 5-Years
  • RD -0.006 (95CI -0.024, 0.11)
  • OR 0.9 (95CI 0.78, 1.14)

There is no difference in survival from the 11
RCTs that reported both 1 and 5 year survival
Single-vessel vs. Multi-vessel Disease
  • 7 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 (95CI -5 to 2) among balloon
    trials and was 0.1 greater for PCI recipients
    (95CI -4 to 4) among stent trials.
  • MVD trials survival 0.6 greater for CABG
    recipients (95CI -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
Heterogeneity statistics Q-value 15.0, p-value
0.13, I-squared 33.3.
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, plt0.0001 at 1-, 3-, and
Freedom From Repeat Revascularization
  • 1-yr PCI recipients required 24 more repeat
    procedures than CABG recipients (p lt0.0001).
    5-yr This difference climbed to 33
  • Statistically heterogeneous outcome.

Freedom from Repeat Revascularization
Balloon Angioplasty
Bare Metal Stents
  • At 5-yrs the gap between PCI and CABG narrows
    somewhat among the stent trials compared to the
    balloon trials.

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.

  • 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
  • Same trends in both balloon and stent trials.

Comparative Cost Data
Comparative Effectiveness Results
  • Procedural outcomes
  • Long-term outcomes
  • Subgroup analyses

Max is a 79 yo man with well controlled HTN,
hypercholesterolemia, afib, and diet
controlled-DMknowing 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
  • Lower power statistic the common test strategy
    of treatment by interaction p-values

Outcomes in Key Subgroups Age
  • All 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,
  • -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 Gender
  • Gender 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

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 95CI 0.51 to
1yr Survival for Patients by Diabetes Status
Survival at 1 year for Patients with Diabetes
Survival at 1 year for Patients Without Diabetes
5yr Survival for Patients by Diabetes Status
Survival at 5 years for Patients with Diabetes
Survival at 5 years for Patients Without Diabetes
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 CAD
  • BARI 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
  • 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
  • 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 Grafts
  • Use of IMAs ranged from 37 in the early GABI
    study to 90 in the more recent trials.

1 Year
5 Years
Favors PCI
Favors CABG
Favors PCI
Favors CABG
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).
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

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.

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.
Todays Talk
  • Background on the procedures
  • Methodological issues
  • Results
  • Conclusions and next steps

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
  • 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.

  • 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
  • Only a few trials specifically reported outcomes
    by number of diseased vesselsthese 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.

  • 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 Thanks
  • Collaborators
  • Allison Gienger
  • Kathy McDonald
  • Vandana Sundaram
  • Doug Owens
  • Marco Perez
  • Robin Varghese
  • John Kapoor
  • Reza Ardehali
  • Moira McKinnon
  • Christopher Stave
  • Ingram Olkin
  • Olga Saynina
  • Robert Jones
  • Funding Agencies AHRQ and VA
  • Photo Credit Cynthia Yock
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