STEMI vs. NSTEMI vs. STABLE CAD Post PCI Optimal DAPT …/media/Non-Clinical/Files-PDFs-Excel... ·...
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STEMI vs. NSTEMI vs. STABLE CAD – Post
PCI Optimal DAPT Duration:Scoring the Complexity of Stenting and Disease
Robert W. Yeh, MD MSc FACCSmith Center for Outcomes Research in Cardiology
Beth Israel Deaconess Medical CenterHarvard Medical School
DAPT Guidelines
2016 ACC/AHA Updated Guidelines on Dual Antiplatelet Therapy2014 ESC/EACTS Guidelines on Myocardial Revascularization
Stable CAD
ACS
The challenge of separating bleeding and ischemic risk
The DAPT Study Results
• In the DAPT Study, continuation of dual antiplatelet therapy beyond 12 months reduced
ischemic complications after coronary stenting compared with aspirin alone, yet increased
moderate or severe bleeding.
Mauri, Kereiakes, Yeh et al. NEJM. 2014 Dec 4:371:2155-66.
-1.0%-1.6%
-2.0%
1.0%0.5%
-3.0%
-2.0%
-1.0%
0.0%
1.0%
2.0%
3.0%HR 1.36
(1.00–1.85) P=0.05
HR 1.61 (1.21–2.16)
P=0.001
HR 0.29(0.17–0.48)
Stent Thrombosis
Death, MI,Or Stroke (MACCE)
MyocardialInfarction
GUSTOMod/Severe
Bleed
Death
HR 0.71 (0.59–0.85)
P<0.001
HR 0.47 (0.37–0.61)
P<0.001
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DAPT Study Randomized
Population
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30% of randomized DAPT
Study patients presented
initially with myocardial
infarction.
46% with ACS.
MACCE Moderate/Severe
Bleeding
Stent Thrombosis
Interaction P=0.69 Interaction P=0.03 Interaction P=0.21
DAPT Study Results Among
Patients with vs. without MI
P<0.001 P<0.001
P<0.001 P=0.08
P=0.005 P=0.007
6Yeh et al., J Am Coll Cardiol. 2015 May 26.
BARC 2, 3, or 5 Bleeding BARC 5 Bleeding
(Fatal Bleeding)
Death
Interaction P=0.13 Interaction P=0.67 Interaction P=0.55
P=0.61 P=0.04
P<0.001 P<0.001
P=0.97 P=0.42
7Yeh et al., J Am Coll Cardiol. 2015 May 26.
DAPT Study Results Among
Patients with vs. without MI
Non-Stent Thrombosis-Related
Myocardial Infarction
Stent Thrombosis-Related
Myocardial Infarction
Interaction P=0.86 Interaction P=0.24
Treatment Effect According to MI Status
Myocardial Infarction Type, 12-30 M follow-up
P<0.001 P<0.001
P=0.04
8
P=0.04
Yeh et al., J Am Coll Cardiol. 2015 May 26.
Meta-analysis in Prior MI
patients
9
Udell et al. European Heart Journal 2015.
NNT/NNH for MI Patients
• NNT to prevent an MI patients = 33• NNH to cause a mod/sev bleed = 90.
• For non-MI patients, NNT = 72. NNH = 111.
Conclusion: The benefits of long term DAPT outweigh the risks in ACS patients
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One size does not fit all
“Long DAPT is Best” Vs. “Short DAPT is Best”
Sometimes long DAPT is better, sometimes shorter DAPT is better
Who is the Average Patient?
Adapted from J. Spertus, with permission
Identifying individual patients with the most to gain or lose from treatment
The Goal of the DAPT Score
• We need a decision tool to identify
whether an individual patient is more
likely to derive benefit or harm from
continuation of dual antiplatelet
therapy beyond 1 year.
• Simultaneously accounting for risks of
ischemia AND bleeding with continued
therapy.
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Methods – Models to Predict
Ischemic and Bleeding Events
Development of 2 Prediction Models within the randomized DAPT Study
population (N=11648).
• Ischemic Model: Myocardial infarction or stent thrombosis between 12-30
months after index PCI. Includes fatal events.
• Bleeding Model: GUSTO moderate or severe bleeding between 12-30
months after index PCI. Includes fatal events.
• Cox regression, stepwise selection among 37 candidate variables,
including randomized treatment arm. In addition, several interaction
terms with treatment arm evaluated. P value of 0.05 for retention. 15
*The ischemia model C-statistic: 0.70 in DAPT Study
**The bleeding model C-statistic: 0.68 in DAPT Study16
Multivariable Prediction ModelsPredictors of Myocardial Infarction or
Stent Thrombosis
Predictors of Moderate/Severe
Bleeding
Predictors of Events HR (95% CI) P HR (95% CI) P
Continued Thienopyridine vs. Placebo 0.52 (0.42 – 0.65) <0.001 1.66 (1.26 - 2.19) <0.001
MI at Presentation 1.65 (1.31 – 2.07) <0.001 - -
Prior PCI or Prior MI 1.79 (1.43 – 2.23) <0.001 - -
CHF or LVEF < 30% 1.88 (1.35 – 2.62) <0.001 - -
Vein Graft PCI 1.75 (1.13 – 2.73) 0.01 - -
Stent Diameter < 3 mm 1.61 (1.30 – 1.99) <0.001 - -
Paclitaxel-Eluting Stent 1.57 (1.26 – 1.97) <0.001 - -
Cigarette Smoker 1.40 (1.11 – 1.76) 0.01 - -
Diabetes 1.38 (1.10 – 1.72) 0.01 - -
Peripheral Arterial Disease 1.49 (1.05 – 2.13) 0.03 2.16 (1.46, 3.20) <0.001
Hypertension 1.37 (1.03 – 1.82) 0.03 1.45 (1.00, 2.11) 0.05
Renal Insufficiency 1.55 (1.03 – 2.32) 0.04 1.66 (1.04, 2.66) 0.03
Age (per 10 years) - - 1.54 (1.34, 1.78) <0.001
The Critical Component of the DAPT Score –
Predicting Net Treatment Effect
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• Predictors of net treatment effect with continued thienopyridine
determined from linear regression and simplified to an integer point
score (DAPT Score)
Predicted Ischemic Event
Rate with Placebo
Predicted Ischemic
Event Rate with Rx
Predicted Net Treatment Effect
(Range from Negative to Positive)
Predicted Risk Reduction in Ischemic Events
(Beneficial Effect)
Predicted Risk Increase in Bleeding Events
(Harmful Effect)
Predicted Bleeding Event
Rate with Rx
Predicted Bleeding Event
Rate with Placebo
The DAPT Score
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Variable Points
Patient Characteristic
Age
≥ 75 -2
65 - <75 -1
< 65 0
Diabetes Mellitus 1
Current Cigarette Smoker 1
Prior PCI or Prior MI 1
CHF or LVEF < 30% 2
Index Procedure Characteristic
MI at Presentation 1
Vein Graft PCI 2
Stent Diameter < 3mm 1
Distribution of DAPT Scores among all
randomized subjects in the DAPT Study
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Q1 Q2 Q3 Q4Q1 Q2 Q3 Q4Q1 Q2 Q3 Q4
Continued Thienopyridine vs. Placebo
Treatment Effect by DAPT Score Quartile
-0.07%
-0.73%
1.97%
-0.06%-0.59%
1.17%
-1.34%
-2.56%
0.69%
-2.18%
-3.48%
0.03%
-4.0%
-3.0%
-2.0%
-1.0%
0.0%
1.0%
2.0%
3.0%
4.0% Stent Myocardial GUSTO Moderate/
Ris
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12
-30
M
Q1 = DAPT Score -2 to 0
Q2 = DAPT Score 1
Q3 = DAPT Score 2
Q4 = DAPT Score > 2
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Q1 Q2 Q3 Q4
Continued Thienopyridine vs. Placebo
Treatment Effect by DAPT Score Quartile
Q1 Q2 Q3 Q4
Net AdverseEvents
Mortality
0.99%1.53%
0.49% 0.37%0.09%
-1.99%
-0.06%
-3.43%-4.0%
-3.0%
-2.0%
-1.0%
0.0%
1.0%
2.0%
3.0%
4.0%
DAPT Score
< 2
DAPT Score
≥ 2
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-30
M
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DAPT Score
< 2
DAPT Score
≥ 2
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Continued Thienopyridine vs. Placebo DAPT Score <2 (Low); N=5731
1.7% vs. 2.3%P=0.07
Continued Thienopyridine
Placebo
10%
8%
6%
4%
2%
0%
Cu
mu
lative
In
cid
en
ce
of S
T/M
I
12 15 18 21 24 27 30Months After Enrollment
3.7% vs. 3.8%P=0.73
Continued Thienopyridine
Placebo
10%
8%
6%
4%
2%
0%Cu
mu
lative
In
cid
en
ce
of
MA
CC
E
12 15 18 21 24 27 30Months After Enrollment
3.0% vs. 1.4%P<0.001
Continued Thienopyridine
Placebo
10%
8%
6%
4%
2%
0%
Cu
mu
lative
In
cid
en
ce
of G
US
TO
Mod
era
te/
Se
ve
re B
lee
d
12 15 18 21 24 27 30Months After Enrollment
Myocardial Infarction or Stent Thrombosis Death, MI, or Stroke (MACCE)
GUSTO
Moderate/
Severe
Bleeding
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Continued Thienopyridine vs. Placebo DAPT Score ≥ 2 (High); N=5917
2.7% vs. 5.7%P<0.001
Continued Thienopyridine
Placebo
10%
8%
6%
4%
2%
0%
Cu
mu
lative
In
cid
en
ce
of S
T/M
I
12 15 18 21 24 27 30Months After Enrollment
4.9% vs. 7.6%P<0.001
Continued Thienopyridine
Placebo
10%
8%
6%
4%
2%
0%Cu
mu
lative
In
cid
en
ce
of
MA
CC
E
12 15 18 21 24 27 30Months After Enrollment
1.8% vs. 1.4%P=0.26
Continued Thienopyridine
Placebo
10%
8%
6%
4%
2%
0%
Cu
mu
lative
In
cid
en
ce
of G
US
TO
Mod
era
te/
Se
ve
re B
lee
d
12 15 18 21 24 27 30Months After Enrollment
Myocardial Infarction or Stent Thrombosis Death, MI or Stroke (MACCE)
GUSTO
Moderate/
Severe
Bleeding
NNT/NNH for High DAPT Score Patients
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0
50
100
150
200
250
300
NNT NNH
For every 1000 patients treated, prevent 30 MIs and cause < 4 bleeds
34
274
70% of patients with any history of MI have DAPT Scores ≥ 2.
Coronary Complexity
Pooled analysis of 6 RCTs
Comparing 3 to 6 months DAPT
Vs. ≥ 12 months DAPT
Complex Features:
3 vessels treated
≥ 3 stents placed
≥ 3 lesions treated
Bifuration with 2 stents
Total stent length > 60 mm
CTO
Individualize Therapy“Decisions about treatment with and duration of DAPT required a thoughtful assessment of the benefit risk ratio, integration of current and future study data, and consideration of patient preference.”
Levine et al. Focused Update on Duration of DAPT. JACC 2016.
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Facilitating “Bedside” Use
Conclusions
• Continuing long-term DAPT entails a tradeoff of risk and benefit, among all patients independent of presentation.– Prior and presented ACS is a factor that influences the benefit of DAPT.– However, among elective, NSTEMI and STEMI pts, some patients likely
to be harmed by long-term DAPT, others likely to benefit.
• Tool like the DAPT Score may by useful in conjunction with clinical judgment and other coronary complexity factors to help individualize therapy.
Thank you!
@rwyeh
Richard and Susan Smith Center for
Outcomes Research in Cardiology
375 Longwood Avenue, 4th Floor
Boston, Massachusetts 02215