Sergio Leonardi L Kristin Newby E Magnus Ohman Paul W Armstrong November 16 th 2010 Chicago IL AHA Scientific Sessions Disclosures Information None of the authors have relevant financial disclosures ID: 271616
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Implementation of ESC/ACC Definition of Myocardial Infarction in Contemporary, Large RCTs: A Systematic Review
Sergio Leonardi, L. Kristin Newby, E. Magnus Ohman, Paul W. Armstrong.
November 16
th
2010
Chicago, IL – AHA Scientific SessionsSlide2
Disclosures Information
None of the authors have relevant financial disclosuresSlide3
Background
Myocardial Infarction (MI) is a key endpoint in RCTs evaluating new
therapies
However heterogeneity in MI definition may affect comparisons across RCTs as well as meta-
analyses
The 2000 ESC/ACC MI definition
1
consensus recommendations were aimed at resolving
this1: Antman E, Bassand J-P, Klein W, et al. Myocardial infarction redefined -- A consensus document of The Joint European Society of Cardiology/American College of Cardiology committee for the redefinition of myocardial infarction: The Joint European Society of Cardiology/ American College of Cardiology Committee. J Am Coll Cardiol 2000;36:959-69.
Hence, we explored the extent to which they are applied in contemporary, large, cardiovascular RCTsSlide4
Methods – Search Criteria
We performed a systematic review of CV RCTs with > 500 patientswhere MI was part of the primary endpoint
initiated after the 2000 ESC/ACC MI redefinition
publication
Search terms included:
A
cute
C
oronary SyndromeMyocardial InfarctionCoronary Artery DiseasePercutaneous
C
oronary
I
ntervention
C
oronary
A
rtery
B
y-pass
G
raftingSlide5
Metrics of Guideline Recommendations Adherence
Adherence
to 2000
ESC/ACC consensus document
was captured
using 3
of its key
recommendations
Use of troponin to define endpoint MISeparate reporting of spontaneous and procedural MIEnzymatic infarct size reporting (i.e., AUC or peak biomarker value)We evaluated: % RCTs referencing the 2000 ESC/ACC consensus document &% of RCTs referencing any consensus document endorsed by the ACC, AHA, or ESCSlide6
Flowchart for Study Screening Process
Time
Period Explored
:
Sep 1, 2000 to May 5, 2010
Exclusion if
any
of the following:
1. ≤ 500 pts enrolled2. MI not part of the primary EP3. Started before Sep 2000Slide7
Summary of RCTs Evaluated
2,729 RCTs screened
134 (5%) met inclusion
criteria
Of these
55
(41%)
RCTs had primary results including 297,467 pts, 13,526 end-point MIs and a median FU of 9 months (IQR: 1-15.6 months)9 additional RCTs had design paper published but not primary results (from which MI def’n
can be assessed
)
MIs
contributed a median
40.3%
(IQR: 22.9, 61.2)
of events in the primary composites
, a % that decreased with increasing number of compone
nts Slide8
Relationship Between Proportion MI Events Within Primary Endpoint and Number of Components
2 Comp (n=
7
RCTs)
3 Comp
(n=28
RCTs) 4 Comp (n=11 RCTs) >4 Comp (n=8 RCTs)Proportion of MI events within the primary EPSlide9
Index Event At Enrollment into RCTs Slide10
Referencing of Consensus Documents in RCTs
55 RCTs with primary results + 9 Only Design = 64 RCTs evaluable.
Overall,
31.2% of RCTs
(20/64)
sourced a consensus documentSlide11
Use of Troponin to Define Endpoint MI
12
RCTs (18.7%) had no MI definition published
52
residual
RCTs evaluable for troponin use
38.5%
(20/52) used Troponin to define MI [66.7% (12/18) among those that referenced a consensus document]Only 1 used troponin for procedural MI2 used troponin only if CK-MB not availableNo RCT specified the 99th
percentile as the MI decision limitSlide12
Separate Reporting and Infarct Size
Only 1
/55
RCT
(1.8%)
reported separately spontaneous and procedural MI
in
the primary results
NO RCTs reported infarct size, either by area under the curve of biomarker release or peak valuesSlide13
Conclusions
MI contributes substantially to primary outcome measures in contemporary large RCTs
However, there is surprisingly little implementation of ESC/ACC recommendations for MI definition and reporting
Appropriate
strategies for uniform implementation of the MI endpoint in cardiovascular
RCTs
appear urgently requiredSlide14Slide15
Contribution of MI to Primary Endpoint in RCTs by Revascularization Groups
Group 1: Interventional RCTs All patients underwent a coronary revascularization (PCI/CABG) either as part of the randomized intervention or as inclusion criterion
Rate of coronary revascularization ≈ 100%
Group 2:
ACS RCTs A coronary revascularization could be performed as part of the index enrolling ACS but not required
Median Revascularization rate 62.8% Group 3: Other RCTs Broad group of RCTs were a coronary revascularization was possible, but not expected Median Revascularization rate 3.8 % Supplementary Slide 1Slide16
MI Events in RCTs by Revascularization Groups
Interventional RCTs (N=
31
RCTs)
ACS RCTs
(N=13
RCTs) Other RCTs (n=11 RCTs)Proportion of MI events within the primary EPSupplementary Slide 2Slide17
Use of Troponin to Define MI According to Revascularization GroupSlide18
Adjust. MI Rate in RCTs by Revascularization Groups
Interventional RCTs (N=
31
RCTs)
ACS RCTs
(N=13
RCTs) Other RCTs (n=11 RCTs)MI %* N of componentsSupplementary Slide 3Slide19
Key features of MI definition in the 10 largest RCTs studied
Supplementary Slide 4