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

5

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

10

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.

14

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

17

• 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

19

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

20

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/

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-30

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Q1 = DAPT Score -2 to 0

Q2 = DAPT Score 1

Q3 = DAPT Score 2

Q4 = DAPT Score > 2

21

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

21

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-30

M

21

DAPT Score

< 2

DAPT Score

≥ 2

22

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

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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

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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

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of G

US

TO

Mod

era

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Se

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lee

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12 15 18 21 24 27 30Months After Enrollment

Myocardial Infarction or Stent Thrombosis Death, MI, or Stroke (MACCE)

GUSTO

Moderate/

Severe

Bleeding

23

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

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of G

US

TO

Mod

era

te/

Se

ve

re B

lee

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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

24

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.

27

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!

ryeh@bidmc.harvard.edu

@rwyeh

Richard and Susan Smith Center for

Outcomes Research in Cardiology

375 Longwood Avenue, 4th Floor

Boston, Massachusetts 02215