Interventional Cardiology Board Review:

Antiplatelet Therapies
2015
Joseph M. Sweeny, MD
Assistant Professor of Medicine
Division of Cardiology
Interventional Cardiology, Cardiac Catheterization Laboratory
Mount Sinai School of Medicine
Mount Sinai Medical Center
New York, New York
 Key References
• Foundation/American Heart Association Task Force on Practice
Guidelines Replacing the 2011 Focused Update): A Report of the
American College of Cardiology Unstable Angina/Non-ST-Elevation
Myocardial Infarction (Updating the 2007 Guidelines) Circulation.
2012;126:875-910

• 2013 ACCF/AHA Guideline for the Management of ST-Elevation

Myocardial Infarction: A Report of the American College of Cardiology
Foundation/American Heart Association Task Force on Practice
Guidelines J Am Coll Cardiol. 2013;61(4):e78-e140. doi:10.1016/j.jacc.2012.11.019

• Antithrombotic Therapy and Prevention of Thrombosis,9th ed:

American College of Chest Physicians Evidence-Based Clinical
Practice Guidelines. Chest 2012;141(2) (Suppl)e89S
 Question 1
• Which of the following antiplatelet agents
interact directly with platelet surface
membrane receptors?
• A) Clopidogrel
• B) Prasugrel
• C) Aspirin
• D) Vorapaxar
• E) A and B
• F) A, B and D
 Question 1
• Which of the following antiplatelet agents
interact directly with platelet surface
membrane receptors?
• A) Clopidogrel
• B) Prasugrel
• C) Aspirin
• D) Vorapaxar
• E) A and B
• F) A, B and D
 Antiplatelet Agents 2015

Desai NR, Bhatt DL. JACC Cardiovasc Interv. 2010;3(6):571-583.

 Vorapaxar (Zontivity)

-Oral, potent, selective PAR-1

antagonist
-Inhibits thrombin-induced PltAgg
-Metabolism via CYP3A4
-No renal clearance
-Long t1/2 >100 hours

• N= 26,449
• Prior MI, CVA or PAD
• 2.5mg vs placebo
• Mod/severe bleeding 4.2% vs 2.5% (increase ICH), ~80% prior MI on DAPT
 Vorapaxar (Zontivity)

TRACER Trial
• N=12,944 with ACS
• 1°EP in 18.5% vs 19.9% (P=0.07)

• No significant reduction in 1°EP

• Significant increase major
• bleeding and ICH (1.1 vs 0.2%)
 Question 2
• Which of the following statements is false regarding
platelet physiology?
• A) Platelets are nucleated cell fragments released into
blood from bone marrow magakaryocytes, regulated
by thrombopoetin and have a life span of 10 days.
• B) Platelet adhesion is mediated primarily by von
Willebrand factor (vWF)
• C) Platelet activation results from several agonists that
bind to their respective membrane receptors on
adherent platelets and release prepackaged
granules of agonists.
• D) Platelet aggregation involves fibrinogen or vWF
binding to specific membrane receptors in GPIIb/IIIa
complex to form platelet thrombus.
 Question 2
• Which of the following statements is false regarding
platelet physiology?
• A) Platelets are nucleated cell fragments released into
blood from bone marrow magakaryocytes, regulated
by thrombopoetin and have a life span of 10 days.
• B) Platelet adhesion is mediated primarily by von
Willebrand factor (vWF)
• C) Platelet activation results from several agonists that
bind to their respective membrane receptors on
adherent platelets and release prepackaged
granules of agonists.
• D) Platelet aggregation involves fibrinogen or vWF
binding to specific membrane receptors in GPIIb/IIIa
complex to form platelet thrombus.
 Platelets & Pathophysiology in CAD

Clumping
Anucleated
Disc shaped cell fragments
Circulate
Source of GF (Granules) CF 5, 8
ADP, ATP
TxA2, Fib

Receptors:
GP 2B/3A,P2Y12
TxA2
PAR-1

Endothelial injury Vessel wall

 Question 3
• Which of the following statements is correct
regarding the risk of stroke associated with
Abciximab among patients undergoing PCI.

• A) Abciximab in addition to aspirin and heparin does

not increase the risk of stroke in patients undergoing
PCI
• B) Abciximab in addition to aspirin and heparin
increases the risk of stroke in patients undergoing
PCI
• C) Abciximab in addition to aspirin and heparin
decreases the risk of stroke in patients undergoing
PCI
 Question 3
• Which of the following statements is correct
regarding the risk of stroke associated with
Abciximab among patients undergoing PCI.

• A) Abciximab in addition to aspirin and heparin does

not increase the risk of stroke in patients undergoing
PCI
• B) Abciximab in addition to aspirin and heparin
increases the risk of stroke in patients undergoing
PCI
• C) Abciximab in addition to aspirin and heparin
decreases the risk of stroke in patients undergoing
PCI
Akkerhuis combined analysis
EPIC, CAPTURE, EPILOG & EPISTENT

• Abciximab a potent
platelet inhibitor
(aggregation)
• 8555 patients
undergoing PCI
• Risk of hemorrhagic or
non hemorrhagic CVA at
30 days. No difference
• Standard vs low dose
heparin 100 vs 70U/kg)

Akkerhuis KM, et al. JAMA 2001;286:78

 CADILLAC TRIAL
Comparison of Angioplasty with Stenting, with or without
Abciximab in Acute MI

Stone, GW et al. NEJM;346:957

HORIZONS AMI
 Question 4
• Which of the following glycoprotein
IIb/IIIa inhibitors has the shortest half-
life but longest duration of therapy?
• A) Tirofiban
• B) Eptifibatide
• C) Abciximab
• D) Lamifiban
 Question 4
• Which of the following glycoprotein
IIb/IIIa inhibitors has the shortest half-
life but longest duration of therapy?
• A) Tirofiban
• B) Eptifibatide
• C) Abciximab
• D) Lamifiban
Pharmacodynamic Characteristics
of GPIIb/IIIa Inhibitors
 Question 5
• Which of the following statements on the use of long-term dual
antiplatelet therapy post DES implantation is correct?
• A) Due to the possibiltiy of DES late stent thrombosis, DAPT is
recommended indefinitely.
• B) Based on the results of CHARISMA trial, aspirin and
clopidogrel should be administered for at least 3 years in
patients with an ACS independent of implantation of DES.
• C) At 1 year, clopidogrel can be discontinued but the aspirin dose
should be increased to 325mg daily
• D) In patients at particular high risk of stent thrombosis or in
patients in whom a stent thrombosis would be associated with
a catastrophic outcome (left main stent), DAPT may be
extended after 12 months.
• E) Following DES implantation, aspirin should be discontinued at
12 months and clopidogrel administered indefinitely.
 Question 5
• Which of the following statements on the use of long-term dual
antiplatelet therapy post DES implantation is correct?
• A) Due to the possibiltiy of DES late stent thrombosis, DAPT is
recommended indefinitely.
• B) Based on the results of CHARISMA trial, aspirin and
clopidogrel should be administered for at least 3 years in
patients with an ACS independent of implantation of DES.
• C) At 1 year, clopidogrel can be discontinued but the aspirin dose
should be increased to 325mg daily
• D) In patients at particular high risk of stent thrombosis or in
patients in whom a stent thrombosis would be associated with
a catastrophic outcome (left main stent), DAPT may be
extended after 12 months.
• E) Following DES implantation, aspirin should be discontinued at
12 months and clopidogrel administered indefinitely.
 Stent Thrombosis (ST):
A Rare, Serious Adverse Event
Can Occur Any Time Post-Stent Implantation

Very
Late ST
(>1 yr)

Late ST
(1-12months)

Subacute ST
(24h to 30d)

Acute ST
(<24 hours)
Limited DAPT duration Indefinite DAPT duration
 Primary Endpoint
Overall Death, MI or CVA
CEC adjudicated
24 mo DAPT 6 mo DAPT
12

10.1
No benefit by prolonging DAPT treatment 10.0

8
P=0.91
%

Hazard Ratio: 0.98 (0.74-1.29)

0
0 180 360 540 720
No. at Risk
24-Month Clopidogrel 987 925 884
6-Month Clopidogrel 983 919 881
 Key Safety Endpoint
Type II, III or V BARC bleeding
CEC adjudicated
24 mo DAPT 6 mo DAPT
12

P=0.00018

8
Questions if initial recs overemphasized 7.4
the benefit over the risk of long-term DAPT
%

4
3.5

Hazard Ratio: 0.46 (0.1-0.69)

0
0 180 360 540 720
No. at Risk
24-Month Clopidogrel 987 925 884
6-Month Clopidogrel 983 919 881
 OPTIMIZE Landmark at 3M: NACCE
(All-Cause Death, MI, Stroke, Major Bleeding)
After Zotarolimus-Eluting Stents
15 3M DAPT
Incidence of NACCE (%)

12M DAPT

10 P = 0.86 P = 0.91
HR 1.03 HR 1.03
(0.71 – 1.51) (0.66 – 1.60)

5
3.5
3.3 2.6
2.6
0
0 3 6 9 12
Time After Initial Procedure (Months)
Month 0 1 3 6 12
No. at risk 1563 1520 1504 1468 1384
No. events 18 25 11 18 21
No. at risk 1556 1514 1497 1466 1381
No. events 16 25 11 16 22

Feres, F, et al. JAMA 2013 Dec 18;310(23):2510-22

 DAPT Study
Stent Thrombosis

Dual antiplatelet therapy beyond 1 year after placement of a drug-eluting stent, as compared
with aspirin therapy alone, significantly reduced the risks of stent thrombosis and major adverse
cardiovascular and cerebrovascular events but was associated with an increased risk of bleeding.

Mauri L. et al. NEJM Nov 2014

 Guidelines
Class I Recommendations
The duration of P2Y12 inhibitor therapy after PCI:

1. In ACS patients receiving BMS or DES, P2Y12 inhibitor

therapy should be given for at least 12 months. Options are
ticagrelor 90 mg twice daily, clopidogrel 75 mg daily,
prasugrel 10 mg daily. (Level of Evidence: B)

2. In Non-ACS patients receiving DES, clopidogrel 75 mg daily

should be given for at least 12 months if not at high bleeding
risk. (Level of Evidence: B)

3. In Non-ACS patients receiving BMS, clopidogrel should be

given for minimum of 1 month and ideally up to 12 months
(unless at increased bleeding risk; then should be given for 2
weeks). (Level of Evidence: B)
2011 PCI Guidelines. Circulation. 2011;124:e574-e651
 Question 6
• In the landmark CURE trial, what was
the relative risk reduction (RR)
observed in those patients with
NSTEMI randomized to clopidogrel +
Aspirin ?
• A) 5%
• B) 15%
• C) 20%
• D) 25%
 Question 6
• In the landmark CURE trial, what was
the relative risk reduction (RR)
observed in those patients with
NSTEMI randomized to clopidogrel +
Aspirin ?
• A) 5%
• B) 15%
• C) 20%
• D) 25%
 Primary End Point: MI/Stroke/CV Death
0.14 20%
Placebo
Cumulative Hazard Rate

Relative
0.12 + Aspirin Risk
(n=6303) Reduction
0.10

0.08
Clopidogrel
0.06 + Aspirin P < 0.001
(n=6259) N=12,562
0.04

0.02
Higher bleeding complications 8.5 vs. 5.0, p < 0.001
0.00
0 3 6 9 12
Months of Follow-up

Yusuf S, et al. N Engl J Med. 2001;345:494-502.

 Question 7
• Which of the following statements regarding
Prasugrel is false?
• A) Prasugrel is a third generation thienopyridine and
has more potent, consistent and rapid inhibition of
P2Y12 receptor.
• B) In pre-specifid subgroup analysis, treatment with
prasugrel seemed to be effective in subjects with
diabetes.
• C) Prasugrel does not seem to be prone to alterations
in pharmacokinetics, pharmacodynamics or clinical
efficacy on the basis of genotype.
• D) In the TRITON-TIMI 38 trial as a whole, those
patients >75 yo, >60kg or those with prior TIA or
CVA benefited more with clopidogrel vs prasugrel
 Question 7
• Which of the following statements regarding
Prasugrel is false?
• A) Prasugrel is a third generation thienopyridine and
has more potent, consistent and rapid inhibition of
P2Y12 receptor.
• B) In pre-specifid subgroup analysis, treatment with
prasugrel seemed to be effective in subjects with
diabetes.
• C) Prasugrel does not seem to be prone to alterations
in pharmacokinetics, pharmacodynamics or clinical
efficacy on the basis of genotype.
• D) In the TRITON-TIMI 38 trial as a whole, those
patients >75 yo, >60kg or those with prior TIA or
CVA benefited more with clopidogrel vs prasugrel
 Mechanism of Action of Prasugrel

• More rapid onset (0.5h)

• Prolonged antiplatelet
effect

• More consistent
antiplatelet activity

Intestine
(60%)

1A2, 2C19, 3A4, 2C19 (15%)

2B6 2C9, 2B6

Bhatt DL. N Engl J Med. 2009;361:940-942.

 Prasugrel and Platelet
Inhibition

Wiviott SD, et al. Circulation 2007

 TRITON – TIMI 38
15

↓138 events
HR 0.81
(0.73-0.90)
(CV death, MI, stroke, %)

P=0.0004
10
Primary Endpoint

NNT = 46

• 13,600 ACS (STEMI & NSTEMI)

• Randomized to Clop vs Pras
5 • 1ºEP CV Death/MI/CVA
↑35 events
HR 1.32
(1.03-1.68)
P=0.03
NNH = 167

30 60 90 18 270 360 450

Days
Adapted from Dr. E Antman and Wiviott SD et al. N Engl J Med. 2007;357:2001-2015.
 Prasugrel vs Clopidogrel
stratified by Diabetes status

Primary efficacy end point (cardiovascular death/nonfatal MI/nonfatal stroke)

stratified by diabetic status Wiviott SD, et al. Circulation 2008
 Question 8
• Which of the following statements are false
regarding Ticagrelor?
• A) Ticagrelor provides more potent, rapid and
consistent platelet inhibition compared with
clopidogrel.
• B) Ticagrelor’s mechanism of action is via irreversible
nonthienopyridine ADP receptor antagonism.
• C) At 1 year there was a highly significant 16% RRR in
the rate of CV death, MI or stroke with ticagrelor
compared to clopidogrel.
• D) Ticagrelor was associated with an increased rate of
major bleeding not related to CABG as well as
numerical excess of intracranial hemorrhage.
 Question 8
• Which of the following statements are false
regarding Ticagrelor?
• A) Ticagrelor provides more potent, rapid and
consistent platelet inhibition compared with
clopidogrel.
• B) Ticagrelor’s mechanism of action is via irreversible
nonthienopyridine ADP receptor antagonism.
• C) At 1 year there was a highly significant 16% RRR in
the rate of CV death, MI or stroke with ticagrelor
compared to clopidogrel.
• D) Ticagrelor was associated with an increased rate of
major bleeding not related to CABG as well as
numerical excess of intracranial hemorrhage.
 Mechanism of Action of Ticagrelor

No hepatic
activation

Ticagrelor and cangrelor (short acting iv agent) bind reversibly to

an allosteric modulation site distinct from the ADP site

Bhatt DL. Nature Reviews Cardiology. 2009;6:737-738.

van Giezen JJ. Eur Heart J Suppl. 2008;10:D23-D29.
 Primary Composite Endpoint
13 (Death, MI, CVA)
12 Clopidogrel 11.7
Cumulative Incidence (%) 11
10 9.8
9
Ticagrelor
8
7
HR 0.84, 16% RRR (95% CI 0.77–
6
5 0.92), P = 0.0003
4
• N = 18,624
3 • NSTEMI-ACS (moderate-to-high risk) STEMI (if primary PCI)
2 • randomized within 24 hours of index event
1 • Primary endpoint: 6-12m CV death + MI + Stroke
0 • Primary safety endpoint: Total major bleeding

0 60 120 180 240 300 360

Days after Randomization
No. at risk
Ticagrelor 9,333 8,628 8,460 8,219 6,743 5,161 4,147
Clopidogrel 9,291 8,521 8,362 8,124 6,743 5,096 4,047

Wallentin L, et al. N Engl J Med. 2009;361(11):1045-1057.

 Secondary Efficacy Endpoints
Myocardial Infarction Cardiovascular Death
7 6.9 7
Clopidogrel
6 6
5.8
Cumulative Incidence (%)

Cumulative Incidence (%)

5 5 Clopidogrel 5.1
Ticagrelor
4 4 4.0

3 Ticagrelor
3

HR 0.84 (95% CI 0.75–0.95), 2

2 HR 0.79 (95% CI 0.69–0.91),
P = 0.005 P = 0.001
1
1

0
0

0 60 120 180 240 300 360 0 60 120 180 240 300 360
Days after Randomization Days after Randomization

Wallentin L, et al. N Engl J Med. 2009;361(11):1045-1057.

 PLATO Trial
Non-CABG Bleeding Risk

NEJM 2009;361:1045
 Question 9
• Which of the following are true regarding
platelet reactivity testing in routine clinical
practice?
A) The utility of Platelet reactivity testing has been
validated in randomized clinical trials.
B) Patients with High on Treatment Platelet
Reactivity (HTPR) have a higher CV event rate.
C) Increasing Clopidogrel dosing has been shown
to reduce CV events in patient with HTPR.
D) Switching from Clopidogrel to Prasugrel or
Ticagrelor has been shown to reduce CV
events in HTPR.
 Question 9
• Which of the following are true regarding
platelet reactivity testing in routine clinical
practice?
A) The utility of Platelet reactivity testing has been
validated in randomized clinical trials.
B) Patients with High on Treatment Platelet
Reactivity (HTPR) have a higher CV event rate.
C) Increasing Clopidogrel dosing has been shown
to reduce CV events in patient with HTPR.
D) Switching from Clopidogrel to Prasugrel or
Ticagrelor has been shown to reduce CV
events in HTPR.
 Variable Response to Clopidogrel

Gurbel PA, et al., Circulation 2003;107:2908-2913

 Variables causing HTPR
(High on-clopidogrel Treatment
Platelet Reactivity)
Non-genetic factors
• Medical Non-compliance
• Clinical factors and co-morbidities
Age
Renal insufficiency/CKD
Gender
BMI
Diabetes
ACS
Cardiogenic shock
Smoking
• Co-medication:
PPI (proton pump inhibitors)
Calcium-cannel blockers
Statins
Genetic factors
• CYP2C19 gene variants
CYP2C19*2
CYP2C19*17 (↑bleeding risk)
CYP2C19*3, *4, *5, *6, *7, *8
• CYP3A4 gene variants
• CYP3A5 gene variants
• ABCB1/MDR1 gene variants
• P2Y12 gene variants
• Paraoxonase-1 (PON-1 Q192R) gene
variants
 HTPR and risk for recurrent CV
events

Matetzky S, et al. Circulation2004;109:3171

 GRAV TAS
Results
CV death, MI, or Stent Thrombosis, %

4
• Same rate of CV death, MI, or stent
thrombosis in 2 groups (P = 0.98)
(P = 0.98)
• GUSTO moderate or severe bleeding:
1.4% HD vs. 2.3% standard, respectively
2.3 2.3
(P = 0.10)
2

0
primary outcome
High
clopidogrel
dose
ARCTIC TRIAL 2012
Personalized medicine is an important goal for both patients
And physicians, but it appears that it is difficult goal to reach
for antiplatelet therapy
Conclusions
• Patients with high residual platelet
reactivity after PCI with DES did not
benefit from high-dose clopidogrel
• High-dose clopidogrel for 6 months did
Standard not reduce the primary ischemic outcome
clopidogrel dose
• GUSTO moderate or severe bleeding was
not increased
• Routine testing of platelet reactivity after
PCI is not warranted

Presented by Dr Matthew Price at AHA 2010

Adapted from http://www.cardiosource.org/Science-And-Quality/Clinical-Trials.aspx
 Question 10
• Which of the following statements are not true
regarding CYP2C19 polymorphism gentotype in
clopidogrel metabolism?
• A) Testing for 2C19 alleles has been shown to alter
clinical outcomes and can be tested in ~1 hour
• B) Clopidogrel is a pro-drug that is activated through a 2
step hepatic process
• C) Carriers of CYP2C19*2 reduced function allele have
significantly reduced active thiol metabolite of clopidogrel
• D) Carriers of *2 allele have higher rates of stent
thrombosis.
• E) All of the above
 Question 10
• Which of the following statements are not true
regarding CYP2C19 polymorphism gentotype in
clopidogrel metabolism?
• A) Testing for 2C19 alleles has been shown to alter
clinical outcomes and can be tested in ~1 hour
• B) Clopidogrel is a pro-drug that is activated through a 2
step hepatic process
• C) Carriers of CYP2C19*2 reduced function allele have
significantly reduced active thiol metabolite of clopidogrel
• D) Carriers of *2 allele have higher rates of stent
thrombosis.
• E) All of the above
 Genetic Variations and Clinical
Outcomes in Patients Taking Clopidogrel
1 Efficacy Outcome Stent Thrombosis

Definite or Probable Stent Thrombosis (%)

12.1 3
12 Carriers of 2C19
11 reduced-function 2.6
allele Carriers of 2C19
CV death, MI or stroke (%)

10 P = 0.01 reduced-function
9 allele
8.0 2
8
7 P = 0.02
6 Non-carriers of 2C19
reduced-function allele
5
Non-carriers of 2C19
4 1 reduced-function allele 0.8
3
2
1
0 0
0 30 90 180 270 360 450 0 30 90 180 270 360 450
Days Since Randomization Days Since Randomization

Mega JL, et al. & Sabatine MS. N Engl J Med. 2009;360:354-362.

 Genotyping & Platelet Function Testing
What are we left with?
• 2011 ACCF/AHA Focused Update UA/NSTEMI
(Updating the 2007 Guideline)
– Class IIb recommendation for platelet
function testing in patients undergoing PCI
– “A selective, limited approach to platelet
genotype assessment and function testing is
the more prudent course until better clinical
evidence exists to provide a more
scientifically derived recommendation.”

Wright, et al. J AM Coll Cardiol. 2011

 Question 11
• A 65 year-old female with prior GI bleeding
presents with a STEMI and is taken
emergently to the cath lab where a
thrombotic 95% proximal LAD is found.
• She undergoes a bare metal stent
placement (BMS).
• Which of the following is true regarding
this patient’s post-PCI antiplatelet
regimen?
 Question 11
• A) Aspirin 81mg indefinite and clopidogrel
75 mg daily for 1 year.
• B) Aspirin 81mg indefinitely and
clopidogrel 75mg for 1 month
• C) Aspirin 81mg for 1 year and clopidogrel
75mg for 1 month
• D) Aspirin 81mg and clopidogrel 75mg
indefinitely
 Antiplatelet Therapy to Support
Primary PCI for STEMI
I IIa IIb III
Aspirin 162 to 325 mg should be given before primary PCI.

I IIa IIb III

After PCI, aspirin should be continued indefinitely.
 Antiplatelet Therapy to Support
Primary PCI for STEMI
I IIa IIb III P2Y12 inhibitor therapy should be given for 1 year to
patients with STEMI who receive a stent (BMS or DES)
during primary PCI using the following maintenance doses:

• Clopidogrel 75 mg daily; or
• Prasugrel 10 mg daily; or
• Ticagrelor 90 mg twice a day*

*The recommended maintenance dose of aspirin to be used with ticagrelor is 81 mg

daily.
 Question 12
• Which of the following statements is false regarding
treatment of UA/NSTEMI?
• A) The proportion of ACS (UA/NSTEMI) patients
worldwide who are managed medically without
revascularization (PCI or CABG) is 40–60%.
• B) An early invasive strategy is indicated in initialy
stabalized UA/NSTEMI patients who have an
elevated risk for clinical events.
• C) In a UA/NSTEMI patients treated conservatively,
compared to clopidogrel, prasugrel significantly
reduced the frequency of death from CV causes, MI
or stroke.
 Question 12
• Which of the following statements is false regarding
treatment of UA/NSTEMI?
• A) The proportion of ACS (UA/NSTEMI) patients
worldwide who are managed medically without
revascularization (PCI or CABG) is 40–60%.
• B) An early invasive strategy is indicated in initialy
stabalized UA/NSTEMI patients who have an
elevated risk for clinical events.
• C) In a UA/NSTEMI patients treated conservatively,
compared to clopidogrel, prasugrel significantly
reduced the frequency of death from CV causes, MI
or stroke.
 TRILOGY-ACS

Treatment Decision for N = 7,800 < Treatment Decision

Medical Management 75 yrs, determined > 24 hrs OR
determined < 24 hrs chronic Clopidogrel Rx
N ~ 2,500 
75 yrs

Randomize < 24 h
Start/Continue Clopidogrel < 24 h

Randomize between
Clopidogrel Prasugrel 1-7 days
300 mg LD 30 mg LD
75 mg MD 10/5 mg MD* Clopidogrel Prasugrel
75 mg MD 10/5 mg MD*
* 5 mg MD of prasugrel for age  75 yrs or weight < 60 kg

Median duration of treatment ~ 18 months

 Primary Efficacy Endpoint and
TIMI Major Bleeding Through 30 Months
(Age < 75 years; 7243)

HR (95% CI):
Endpoint (%)

0.91 (0.79, 1.05)

P = 0.21

HR (95% CI):
1.31 (0.81, 2.11)
P = 0.27

Roe MT et al NEJM 2012

Good Luck!!