Transcript Prasugrel / Ticagrelor

Is time has come to forget
Clopidogrel and move to
Prasugrel & Ticagrelor?
Vinod Sharma
National Heart Institute
New Delhi
1
Fibrin
2
3
4
Antiplatelet Therapy in ACS-studies
ASA
ASA + Clopidogrel
ASA +
Prasugrel
Reduction
in
Ischemic
Events
- 22%
- 20%
- 19%
Placebo
+ 32%
+ 38%
+ 60%
APTC
CURE
Single
Dual
Antiplatelet Rx Antiplatelet Rx
Increase
in
Major
Bleeds
TRITON-TIMI 38
Higher
IPA
5
6
BLEEDING
THROMBOSIS
7
Optimal Antiplatelet Therapy in ACS
 The combination of Aspirin & Clopidogrel
has been main stay of ACS & PCI antiplatelet
therapy for the past decade.
 The use of this combination is suported by
several large scale studies & physicians
have a large amount of real-world experience
with this combination.
Yusuf S, Zhao F, Mehta SR et al: N Engl J Med. 2001: 345 (7): 494 - 502
8
Benefit of Clopidogrel
NSTEMI
-
CURE 2001
-
PCI – CURE (2001)
STEMI
-
CLARITY – TIMI 28 (2005)
-
PCI – CLARITY (2005)
-
COMMIT (2005)
 Elective PCI
-
THE CREDO Trial (2002)
Clopidogrel to be beneficial in a broad spectrum of CAD. Subground analysis suggest that
pretreatment before PCI provides additional benefit particularly if Clopidogrel is given at
least 6 hours in advance
9
Clopidogrel PreRx
Without GPI
Favors Favors
PreRx No PreRx
Trial
Clopi PreRx
No PreRx
PCI-CURE
27/1039 (2.6)
39/988 (3.9)
CREDO
26/473 (5.5)
34/519 (6.6)
PCI-CLARITY
22/639 (3.4)
30/615 (4.9)
OVERALL
75/2151 (3.5)
103/2122 (4.9)
OR 0.72
0.25
(0.53-0.98)
P=0.03
0.5
1.0
OR (95% CI)
With GPI
P=0.85 for
heterogeneity
by GPI use
Trial
Clopi PreRx
No PreRx
PCI-CURE
14/274 (5.1)
23/357 (6.4)
CREDO
29/427 (6.8)
32/396 (8.1)
PCI-CLARITY
12/288 (4.2)
28/310 (9.0)
OVERALL
55/989 (5.6)
83/1063 (7.8)
OR 0.69
0.25
Sabatine MS et al. ESC 2006
2.0
(0.47-1.00)
P=0.05
0.5
1.0
OR (95% CI)
2.0
10
Optimal Antiplatelet Therapy in ACS
(cont)
 Serious CV events recurs in approximately
11% of patients with ACS, most of which
occurs early after index event.
Wiviott SD, Braunwald E, McCabe CH et al: N Engl J Med 2007: 357 (20): 2001-2015
11
Potential Limitations of Clopidogrel
Requirement for metabolic activation
–Clopidogrel is a prodrug
Slow onset of antiplatelet effect
–Requiring 300-600mg loading doses in acute phase
–16% of patients achieved > 70% IPA by 2 hours
Moderate overall levels of platelet inhibition
–IPA at 2 hrs – 38%; Average IPA ~55%
High variability response within a population
–25-30% with very low levels of platelet inhibition
Irreversible P2Y12 receptor binding
–Require platelet replacement for return of activity
Gurbel PA, et al. Circulation. 2009;120:2577-2585; Plavix® [package insert]. Bridgewater, NJ: Bristol-Myers Squibb/Sanofi Pharmaceuticals
Partnership;2010; Plavix [Summary of product characteristics] Paris, France: Sanofi Pharma Bristol-Myers Squibb SNC; 2010.
12
Individual Response Variability of
Clopidogrel
Number of Patients
20
15
Bleeding risk
Ischemic risk
10
5
0
2.5
12.5
22.5
32.5
42.5
52.5
62.5
72.5
82.5
92.5
7.5
17.5
27.5
37.5
47.5
57.5
67.5
77.5
87.5
97.5
% Platelet Aggregation (LTA-ADP 20mmol/L)
13
Angiolillo DJ et al. Am J Cardiol. 2006;97:38-43.
Clopidogrel Resistance: Worldwide Data
Investigators
n
1. Jaremo et al
18
Patients
PCI
Clopidogrel (LD)
300
Resistance
28%
(J Invest Med. 2002;252:233)
2. Gurbel et al
92
PCI
300
31-35%
(Circulation 2003;107:2908)
3. Muller et al.
105
PCI
600
5-11%
(Thromb Haemost. 2003;89:783)
4. Mobley et al
50
PCI
300
30%
(Am J Cardiol. 2004;93:456)
5. Lepantalo et al.
50
PCI
300
40%
48
PCI
300
44%
60
PCI
300
25%
31
PCI
300
23%
192
PCI
300/600
150
PCI
300
(Eur Heart J. 2004;25-476)
6. Angiolillo et al.
(Thromb Res. 2005;115:101)
7. Matetzky et al.
(Circulation 2004;109:3171.)
8. Dzieweierz
(Kardiol Pol. 2005 ;62:108)
9. Gurbel et al.
8-32%
(J Am Coll Cardiol. 2005;45:1392)
10. Lev Et al.
24%
(J Am Coll Cardiol. 2006;47:27)
Total 616
5-44%
14
Clopidogrel Resistance: Indian Data
Investigators
n
Clopidogrel
Resistance
Clopidogrel
Semi Resistance
Poor
Responders
100
-----
19%
---
39
2.54%
12.70%
---
144
12.50%
----
19.44%
Kar Meena et al
Platelets. 2013;24(4):297-302.
doi:
10.3109/09537104.2012.69399
2. Epub 2012 Jun 21
Kumar S, Saran et al
Indian Heart Journal [2007,
59(2):152-156
Guha Sarder et al
Indian Heart J. 2009 JanFeb;61(1):68-73
15
Limitations – 2
Clopidogrel Resistance; What the studies say ???
Clopidogrel resistance leads to subacute stent thrombosis after
successful PCI
Clopidogrel resistance increases incidence of recurrent CV events (6month follow up period) compared with those without clopidogrel
resistance
without clopidogrel
resistance
with clopidogrel
resistance
0%
44%
Recurrent CV events
(6months follow up)
0% 10% 20% 30% 40% 50%
16
ERIN D. MICHOS, MD;Mayo Clin Proc. 2006;81(4):518-526
Switch To Prasugrel???
17
18
Pharmacology of Prasugrel Vs Clopidogrel
PRASUGREL
Metabolism
Single step process for
activation
CLOPIDOGREL
Hydrolysis by intestinal &
plasma esterases
Inactive terminal metabolite
Residual unhydrolysed drug
metabolism two step
(depends on Cytochrome
P450)
Time to Peak effect
80% of orally absorbed drug
is converted to active drug
10 – 20% of absorbed drug is
available as active drug
Loading dose  more than
80% of IPA by 30 minutes &
peak activity in 4 hours
With loading dose of 600 mg
 4 – 6 hours
Without loading dose  3 – 5
days
IPA at 30 minutes
IPA at 6 hours
19
Pharmacology of Prasugrel Vs Clopidogrel
(contd…)
PRASUGREL
Dose response
CLOPIDOGREL
10 times more potent than
Clopidogrel & 100 times than
Ticlopidine
IPA by 5 mg
75 mg
Significantly greater IPA &
fewer non-responders
--
20
Comparison with Higher
Dose Clopidogrel
IPA (%; 20 mM ADP)
N=201
P<0.0001 for each
IPA (%; 20 mM ADP)
P<0.0001
Prasugrel 60 mg
Clopidogrel 600 mg
Hours
Clopidogrel Prasugrel
150 mg
10 mg
14 Days
21
22
23
Primary Endpoint
CV Death,MI,Stroke
Primary Endpoint (%)
15
Clopidogrel
9.9 %
(643)
10
Prasugrel
5
0
HR 0.77
P=0.0001
HR 0.81
(0.73-0.90)
P=0.0004
NNT= 46
HR 0.80
P=0.0003
ITT= 13,608
0 30 60 90
Days
180
270
12.1 %
(781)
LTFU = 14 (0.1%)
360
450
Prasugrel reduced the primary endpint of CVdeath /MI / or stroke from 12.1 %
in the clopidogrel group to 9.9% over a median fu of 15 months.
24
Balance of
Efficacy and Safety
15
Clopidogrel
Endpoint (%)
CV Death / MI / Stroke
138
events
12.1 HR 0.81
9.9
10
Prasugrel
5
TIMI Major
NonCABG Bleeds
0
Prasugrel
Clopidogrel
0
30 60 90
180
Days
270
360
2.4
1.8
450
(0.73-0.90)
P=0.0004
NNT = 46
35
events
HR 1.32
(1.03-1.68)
P=0.03
NNH = 167
1. Significant reduction in the primary endpoint
2. The rate of TIMI major non CABG bleeds--a key safety endpoint-- which was
25
2.4% with prasugrel and 1.8% with clopidogrel
Diabetic Subgroup
N=3146
18
Clopidogrel
16
CV Death / MI / Stroke
14
Endpoint (%)
17.0
12.2
12
HR 0.70
P<0.001
NNT = 21
Prasugrel
10
8
6
TIMI Major
NonCABG Bleeds
4
2
0
0
30 60 90
Days
180
Clopidogrel
Prasugrel
270
360
2.6
2.5
450
Prasugrel reduced the rate of the primary endpoint in diabetic patients from
17% with clopidogrel to 12.2% of prasugrel patients.
26
Stent Thrombosis
(ARC Definite + Probable)
3
Any Stent at Index PCI
N= 12,844
2.4
(142)
Clopidogrel
Endpoint (%)
2
1.1
(68)
1
Prasugrel
HR 0.48
P <0.0001
NNT= 77
0
0 30 60 90
Days
180
270
360
450
27
Overall Net Clinical Benefit
Prasugrel 60 mg LD/10mg MD vs Clopidogrel 300 mg LD/ 75 mg MD
CV Death /
MI / Stroke
Stent
Thrombosis
uTVR
MI
0%
-10%
-20%
-19%
-24%
-30%
Risk Reduction
-34%
-40%
-50%
-52%
-60%
28
Prasugrel-Dosage
Higher IPA to Support PCI
Prasugrel 60 mg LD/10mg MD vs Clopidogrel 300 mg LD/ 75 mg MD
Efficacy
1. A significant reduction in:
CV Death/MI/Stroke
Stent Thrombosis
uTVR
MI
2. An early and sustained benefit
3. Across ACS spectrum
19%
52%
34%
24%
Safety
Significant
increase in
serious bleeding
(32% increase)
Avoid in pts with
prior CVA/TIA
Net clinical benefit significantly favored Prasugrel
Optimization of Prasugrel maintenance dosing in a minority of patients may help improve the
benefit : risk balance
31
Bleeding Risk Subgroups
Therapeutic Considerations
16%
4%
MD
10 mg
Significant
Net Clinical Benefit with
Prasugrel 80%
32
Prasugrel Boxed Warning
Prasugrel can cause significant, sometimes fatal,
bleeding.
Do not use in patients with active pathological
bleeding or a history of TIA or stroke.
Not recommended in patients > 75 years old because
of risk of fatal and intracranial bleeding and
uncertain benefit, except in high-risk patients
(diabetes or prior MI), in whom its effect appears to
be greater and its use may be considered.
Do not start in patients likely to undergo urgent
CABG, when possible, discontinue at least 7 days
33
before surgery.
Clopidogrel Vs Prasugrel in ACS
The early administrative strategy is hindered by the fact
that patients with ACS represents a heterogeneous
population in terms of risk & prognosis.
Most patients with ACS will undergo PCI but some will be
treated medically & 5-15% of patients will require CABG
TRITON – TIMI 38
99% patients underwent PCI &
94% patients received a minimum of 1 stent.
This study population does not represent the
diversity seen in ACS population.
34
Clopidogrel Vs Prasugrel in ACS
Prasugrel has not been compared with pretreatment with
Clopidogrel in patients with ACS.
TRITON – TIMI 38
-
When patients were administered an early loading
dose or pretreated, the clinical benefit of Prasugrel
over Clopidogrel was found to be non-existent.
Serebruany VL et al: Cardiovasc Revas Med 2011
35
Why importance of Medical Management?
 From EARLY-ACS substudy approximately half of all UA and NSTE
myocardial infarction (NSTEMI) patients do not undergo
revascularization during the initial hospitalization.
36
The TaRgeted platelet Inhibition to cLarify
the Optimal strateGy to medicallY
manage Acute Coronary Syndromes
(TRILOGY ACS) trial
37
38
39
Prasugrel Vs Clopidogrel for ACS without
Revascularization
TRILOGY ACS
Prasugrel was not shown to be superior to
Clopidogrel for reducing the primary end point
during 2.5 years of follow-up after a coronary event
in patients receiving medical therapy without
planned revascularization, even though signs of
intensified platelet inhibition were observed
in the Prasugrel group.
Similar risk of bleeding were observed in two
groups.
40
41
Ticagrelor Pharmacology
 It directly inhibits the P2Y12 receptor without first
undergoing hepatic activation.
 Promptly achieves higher and more consistent
inhibition of platelet aggregation than Clopidogrel
and produces significantly higher platelet inhibition
than Prasugrel.
Gurbel P, et al: ONSET / OFFSET STUDY Circulation 2009
42
Ticagrelor Pharmacology
 A portion of Ticagrelor is converted via CYP3A4 /
CYP3A5 into equipotent active metabolic & is
present at approx. 40% of parent drug concentration.
 Both Ticagrelor & active metabolite inhibits platelet
function by reversibly binding the P2Y12 receptor.
 Reversible binding enables the return of platelet
function upon
thrombopoiesis.
cessation
of
therapy
without
43
Ticagrelor Pharmacology
 Ticagrelor is effectively a precursor of adenosine.
After loss of propyl sulfate and benzodifluoride
structure, the resulting compound is essentially
adenosine.
 Adenosine, endogenous molecule with potential
therapeutic applications.
antiinflammatory
cardioprotective
cerebroprotective
antisclerotic & antifibrotic property
 Ticagrelor has a coronary vasodilatory response by
an adenosine – dependent mechanism.
44
Ticagrelor Pharmacology (Cont)
 The
maximum
antiplatelet
effect
of
Ticagrelor
produces approximately 90% platelet inhibition &
occurs
approximately
2
hours
following
administration of initial dose, whereas the maximal
antiplatelet
effect
of
Clopidogrel
generates
approximately 60% platelet inhibition & occurs 6 – 8
hours after administration of loading dose.
45
Ticagrelor Pharmacology
 The rate of offset of the pharmacodynamic effect of
Ticagrelor is faster than Clopidogrel.
 Platelet
function measurements are similar for
Ticagrelor at 3 days & for Clopidogrel at 5 days
following administration of last dose.
 Pharmacogenomic
variability, that is known to
influence the effect of Clopidogrel does not affect
ticagrelor pharmacology.
46
47
48
49
50
51
52
53
Kaplan-Meier estimated event rates from randomization through 360 days for the primary
efficacy outcome by blinded treatment, randomly assigned, and open-label median
maintenance aspirin (ASA) dose at investigator discretion.
Kenneth W. Mahaffey et al. Circulation. 2011;124:544-554
Geographic Regions - CV Death, MI, Stroke
Geographic
region
Total
patients
KM at month 12
Tic
Clop
HR (95% CI)
Asia /
Australia
1714
11.4
14.8
0.80 (0.61, 1.04)
Central America /
South America
1237
15.2 17.9
0.86 (0.65, 1.13)
Interaction
p-values
0.045
Europe /
13859
Middle East / Africa
8.8
11.0
0.80 (0.72, 0.90)
North America
11.9
9.6
1.25 (0.93, 1.67)
1814
0.01
0.5
1.0
Ticagrelor
better
2.0
Clopidogrel
better
Clopidogrel Vs Ticagrelor
PLATO TRIAL
 Aspirin exerts an antithrombotic effect through inhibition of
platelet cyclooxygenase, thus reducing thromboxane A2 release.
 It also inhibits endothelial release of prostacyclin in a dose-
dependent fashion at daily doses > 80 mg.
 Prostacyclin reduces platelet reactivity and may contribute
snergistically in vivo to the antiplatelet effects of P2Y12
inhibitors.
 Consequently, the therapeutic effects of a higher mean level of
P2Y12 inhibition, as achieved by ticagrelor in the PLATO study
compared with Clopidogrel, may be attenuated when
endogenous prostacyclin production is inhibited.
56
Ticagrelor in the Acute Setting can be Used Across a Broad
Spectrum of ACS Patients
Regardless of Diagnosis
Unstable
Angina
(UA)
Non ST-elevation
MI (NSTEMI)
√
√
ST-elevation
MI (STEMI)
Regardless of Treatment Strategy
Medical
Management
PCI
CABG
√
√
√
√
Across a range of patient characteristics
History of
(Ischemic)
stroke or TIA
Age in years
(18+)
Weight
√
√
√
Sex
Diabetes
status
Genotype
√
√
√
Ticagrelor does not require dose adjustment across ACS patient population
including age (18years and above) and weight
PCI: Percutaneous Coronary Intervention , TIA: Transient Ischemic Attack
ATLANTIC
Administration of Ticagrelor in the cath Lab or in the
Ambulance for New ST elevation myocardial Infarction
to open the Coronary artery
A 30-day study to evaluate the efficacy and safety
of pre-hospital versus in-hospital initiation of
ticagrelor therapy in STEMI patients planned for PCI
NCT01347580
58
ATLANTIC study population and design
STE-ACS planned for PCI
N=1770 (n=1862*)
Written informed consent in mobile care unit
Symptoms of acute MI or more than 30 min but less than 6 h
New persistent ST-segment elevation ≥1 mm in two or more contiguous ECG leads
Randomized, double-blind
Ticagrelor
180 mg loading dose
Pre-hospital
Placebo
loading dose
Placebo
loading dose
In-hospital
Ticagrelor
180 mg loading dose
Primary objective
≥70% ST-segment elevation
resolution pre-PCI
OR
TIMI flow grade 3 of MI culprit
vessel at initial angiography
Ticagrelor 90 mg/bid 30 days
*Consented and randomized
Montalescot G et al. Am Heart J 2013;165:515–522
Montalescot G et al. N Engl J Med September 1, 2014 [Epub ahead of print; DOI: 10.1056/NEJMoa1407024]
59
Definite acute stent thrombosis up to 30 days
Kaplan–Meier curves
Ticagrelor pre-hospital
Ticagrelor in-hospital
Event rate (KM %)
2
1
Ticagrelor pre-hospital 2/906 (0.2%) vs
ticagrelor in-hospital 11/952 (1.2%)
OR 0.19 (95% CI 0.04, 0.86), P=0.02
0
0
2
24 h
P=0.008
4
6
8 10 12 14 16 18 20 22 24 26 28 30
Time (days)
30 days
P=0.02
Montalescot G et al. N Engl J Med September 1, 2014 [Epub ahead of print; DOI: 10.1056/NEJMoa1407024]
60
Non-CABG-related bleeding events
PLATO definitions (safety population)
Pre-hospital
In-hospital
P=NS
P=NS
P=NS
P=NS
P=NS
Major
Minor
P=NS
Composite
of major
and minor
Within 48 h of first dose
Major
Minor
Composite
of major
and minor
After 48 h up to 30 d
Pre-hospital n=908; in-hospital n=950
Events occurring up the date of the last visit (to a maximum of 32 days) are included in the table. Patients could be on study treatment or not
when the event occurred. Patients may be counted in more than one bleeding event category
P values were calculated from Chi-square test
Montalescot G et al. N Engl J Med September 1, 2014 [Epub ahead of print; DOI: 10.1056/NEJMoa1407024]
61
ATLANTIC: summary of results
•
ATLANTIC was an international, multicentre, randomized, double-blind study
in 1862 patients with ongoing STEMI of less than 6 h, comparing pre-hospital
(in-ambulance) versus in-hospital (in-catheterization laboratory) treatment with ticagrelor or
placebo
•
Median time from randomization to angiography was 48 min and median time difference
between the two treatment strategies was 31 min
•
The two co-primary endpoints did not differ between the pre- and
in-hospital ticagrelor groups
•
Post-PCI ST-segment elevation resolution ≥70% was reported in 57.5% and 52.5% of
patients (P=0.055), respectively
• MACE were not different between the two groups
– Mortality was low and there was a numerical imbalance of deaths in the prehospital group vs the in-hospital group (3.3% vs 2.0%). Patient records have been
specifically examined and no treatment related effect can be discerned
– Definite stent thrombosis occurred less frequently in the pre-hospital
arm (0% vs 0.8% in the first 24 hours; 0.2% vs 1.2% at 30 days)
•
Major bleeding event rates at 48 h and 30 days were low and identical between the two
study groups whichever bleeding definitions were used
6262
Montalescot G et al. N Engl J Med September 1, 2014 [Epub ahead of print; DOI: 10.1056/NEJMoa1407024]
Impact of Clopidogrel and Potent P2Y12 inhibitors on
mortality and stroke in patients with ACS or undergoing
percutaneous coronary intervention: a systematic
review and meta-analysis
D Aradi, A Momocsi, A Vorobcsuk et al: Epub 2012:109 Nov.29
Prasugrel / Ticagrelor Vs Clopidogrel (five RCTs)
 Compared
with Clopidogrel, Prasugrel or Ticagrelor
significantly reduced the incidence of CV death (five RCTs),
Myocardial infarction (five RCTs) and the composite of CV
death / MI / stroke, but not stroke (five RCTs) or
intracranial haemorrhage (four RCTs).
 An inverse linear association was observed between the
potency of the P2Y12 receptor inhibitor and the risk of MI, and
CV mortality, but
not stroke
CONCLUSIONS:
Higher Potency P2Y12 receptor inhibition (Prasugrel/Ticagrelor)
was associated with a lower risk of CV death and MI, but not
stroke when compared with Clopidogrel (moderate potency
P2Y12 receptor inhibition)
63
Meta-analysis of RCTs pitting
Prasugrel / Ticagrelor Vs Clopidogrel
Endpoint
Myocardial
infarction
Clopidogrel
(events /
patients)
Prasugrel /
Ticagrelor
(events /
Patients)
ARD,
Prasugrel or
Ticagrelor
Vs
Clopidogrel
Odds ratio
(95% CI)
P value
1624 / 21,330
(7.61%)
1397 /
22,122
(6.32%)
- 1.29%
0.83 (0.74
– 0.93)
< .001
CV Death
926 / 21,330
(4.34%)
809 /
22,122
(3.66%)
- 0.68%
0.86 (0.78
– 0.94)
.002
Total Stroke
236 / 21,330
(1.11%)
253 /
22,122
(1.14%)
+ 0.03%
1.06 (0.88
– 1.26)
.55
Hemorrhagic
Stroke
50 / 20,878
(0.24%)
60 / 21,347
(0.28%)
+ 0.04%
1.16 (0.75
– 1.81)
.49
11.65%
9.97%
- 1.68%
0.85 (0.79
– 0.92)
< .001
Composite: CV
death, MI,
stroke
64
Adjusted indirect comparison meta-analysis of
Prasugrel Vs Ticagrelor for patients with ACS
Giuseppe Biondi Zoccai et al: Int J Cardiol. 2011: 150 (3): 325-331
CONCLUSIONS:
Prasugrel and Ticagrelor are superior to Clopidogrel
for ACS.
Head-to-Head comparison suggests similar efficacy
and safety of Prasugrel and Ticagrelor, but Prasugrel
appears more protective from stent thrombosis,
while causing more bleedings.
65
Prasugrel Vs Ticagrelor
Endpoint
Odds ratio (95% CI)
P value
Composite: death, MI, stroke
0.99 (0.86 – 1.33)
.86
Death
1.22 (0.96 – 1.55)
.11
MI
0.89 (0.75 – 1.06)
.20
Stroke
0.86 (0.55 – 1.33)
.49
Stent thrombosis, definite or
probable
0.64 (0.43 – 0.93)
.02
Major bleeding
1.43 (1.10 – 1.86)
.007
Major bleeding not related to
bypass
1.06 (0.77 – 1.45)
.74
4.30 (1.74 – 10.64)
.002
Major or minor bleeding
1.27 (1.04 – 1.55)
.02
Minor bleeding
1.07 (0.79 – 1.45)
.65
Drug discontinuation
1.03 (0.88 – 1.20)
.73
Major bleeding related to bypass
66
Clopidogrel Vs Presugrel Vs Ticagrelor







Pros of Choosing Clopidogrel
Affordable
Long history of use
Only agent with proven efficacy in patients
undergoing thrombolysis
Once daily dosing
Cons of Choosing Clopidogrel
Response variability with a poor response
associated with increased risk of thrombosis.
Susceptible to genetic variation and drug-drug
interactions.
Questions regarding appropriate dosing.
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Clopidogrel Vs Presugrel Vs Ticagrelor
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Pros of Choosing Prasugrel
Rapid and extensive platelet inhibition
Less susceptible to genetic variation and drug-drug interactions
Reduction in ischemic event rates following PCI Vs Clopidogrel.
Greatest efficacy in patients with diabetes and STEMI
Once daily dosing
Cons of Choosing Prasugrel
Expensive
High risk of major bleeding, especially in patients undergoing
CABG surgery
Coronary anatomy should be defined by angiography before
initiation.
Questionable utility in patients undergoing procedures other
than PCI
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Clopidogrel Vs Presugrel Vs Ticagrelor
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Pros of Choosing Ticagrelor
Rapid and extensive platelet inhibition
Reversible inhibition and rapid offset of effect
Less susceptible to genetic variation and drug-drug interactions
Reduction in ischemic event rates Vs Clopidogrel
Similar overall bleeding risk Vs Clopidogrel
Proven efficacy regardless of treatment strategy
Cons of Choosing Ticagrelor
Expensive
Increased risk of non-CABG surgery bleeding Vs Clopidogrel
Twice-daily dosing.
Dyspnea and ventricular pauses
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70
Is time has come to forget
Clopidogrel and move to
Prasugrel & Ticagrelor?
Ans: Probably not !!!
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An Ideal Drug…
Potent P2Y12
receptor blockade
Less variability in
response especially
in high risk subsets
Lesser drug –
drug interactions
Ideal
Drug
Effective reduction
in primary and
secondary
endpoints
Less (Minimal)
resistance
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Ideal Antiplatelet Drugs
Which of three drugs is best for a given patient?
The answer remains clouded by clinical uncertainty – and the sun
isn’t going to break through soon
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Selection of Antiplatelet Drugs in ACS
Either prasugrel or ticagrelor could be considered
instead of clopidogrel in ACS patients who aren’t at
high risk of bleeding.
Prasugrel appears to be more effective than
Ticagrelor in preventing stent thrombosis, in ACS
patients who are undergoing PCI with drug-eluting
stents and who aren’t at high risk of bleeding,
Prasugrel could be started at the time of PCI.
Ticagrelor could be best for ACS patients without
severe bleeding risk who are to be managed by an
initial conservative therapy.
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Selection of Antiplatelet Drugs in ACS
Ticagrelor may be a better choice than Prasugrel if
urgent CABG is likely.
Clopidogrel may remain the best choice for patients
with high risk of bleeding (e.g. history of stroke,
advanced age, severe renal impairment).
Owing to its low cost, Clopidogrel may be more
attractive than Prasugrel or Ticagrelor in patients
with low risk of ischemia or high risk of bleeding.
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THANK YOU
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