Update on Dual Antiplatelet Therapy CME/Brochure… · Dual antiplatelet therapy...
Transcript of Update on Dual Antiplatelet Therapy CME/Brochure… · Dual antiplatelet therapy...
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Update on Dual Antiplatelet Therapy
Brian J. Corbett DO Assistant Professor of Medicine Cooper
Medical School of Rowan University
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Disclosures
• None
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Questions????????
• Which combination of DAPT?
• Optimal Duration of DAPT?
• Warfarin/NOAC Therapy?
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Platelet inhibition represents the cornerstone of cardiovascular therapy…
CARDIOVASCULAR MEDICINE – KARDIOVASKULÄRE MEDIZIN – MÉDECINE CARDIOVASCULAIRE 2017;20(7–8):169–175
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DAPT: Oral Agents Acetylsalicy
lic acid (ASA)
Ticlopidine hydrochloride
Clopidogrel bisulfate
Prasugrel hydrochloride
Ticagrelor
Trade Name Aspirin1-3 Ticlid®4 Plavix®5 Effient®6 Brilinta®7
Class Salicylate P2Y12 Receptor
Antagonist
P2Y12 Receptor
Antagonist
P2Y12 Receptor Antagonist
P2Y12 Receptor
Antagonist
Formulation Active Drug Active Drug Pro-Drug Pro-Drug Active Drug
Maintenance Dose
75-325 mg daily*
250 mg BID 75 mg daily 10 mg daily 90 mg BID
Reversible No No No No Yes
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Eur Heart J Suppl. 2008;10(suppl_I):I8-I13. doi:10.1093/eurheartj/sun041
Clopidogrel
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Less Bleeding Less Cost
Ischemia
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Why is DAPT so important ?
• Protect the stented vascular segment from the development of stent thrombosis while vascular healing and progressive strut endotheliazation – in-hospital mortality rate of 5% to 10% – 30-day mortality rate of 10% to 25%
JAMA. 2005;293:2126-2130
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Stent Implantation
Endothelial Denudation Medial Dissection Exposure of sub-intimal components Thrombogenecity of metal
Activation of platelets
Thrombosis
Reaction to stent struts (Macrophages and Giant Cells)
Production of: Cytokines Mitogens Chemotaxic factors
Activation of vascular smooth muscle cells
Proliferation and migration of vascular smooth muscle cells
Restenosis
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Stent thrombosis rates reduced with better technique and DAPT…
1. Schatz et al.Circulation. 1991;83:148;2. Fischman et al. N Engl J Med. 1994;331496; 3. Colombo et al. Circulation.1995;91:1676 4. Schomig et al. Circulation. 1994,90:2716; 5. Leon et al. N Engl J Med. 1998;339:1665; 6. Joner et al. J Am Coll Cardiol. 2006;48:193.
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Independent Risk Factors for ST
J. Am. Coll. Cardiol. 2009;53;1399-1409
DAPT
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Interindividual variability in platelet response to clopidogrel after stenting
Michelle O’Donoghue, and Stephen D. Wiviott Circulation. 2006;114:e600-e606
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Source: Wiviott SD et al. NEJM 2007;357:2001-2015
Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel (TRITON-TIMI 38)
0
5
9
60 90 180 270 360 450
HR 0.81, P=0.0004
Prasugrel
Clopidogrel
HR 0.80 P=.001
HR 0.77 P=.001
Days
CV
deat
h, M
I, or
str
oke
% 12.1
9.9 Bleeding Events
C (%) P (%) P-value TIMI major 1.8 2.4 .03 Life threatening 0.9 1.4 .01 Nonfatal 0.9 1.1 .23 Fatal 0.1 0.4 .002 ICH 0.3 0.3 .74
13,608 patients with high-risk ACS scheduled for PCI randomized to clopidogrel (300 mg LD and 75 mg MD) or prasugrel (60 mg LD and 10 mg
MD) for a median of 12 months
7
11
ACS=Acute coronary syndrome, ICH=Intracranial hemorrhage, LD=Loading dose, MD=Maintenance dose
0 30
Prasugrel reduces ischemic events with a higher rate of bleeding
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Net Clinical Benefit Bleeding Risk Subgroups
0.5 1 2
Prior Stroke / TIA
Age > 75
Wgt < 60 kg
Rel Risk
+37%
-1%
+3%
Prasugrell Better Clopidogrell Better
HR
Pint = 0.006
Pint = 0.18
Pint = 0.36
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PLATO: Primary Efficacy Endpoint
Days
9.8% 11.7%
0 60 120 180 240 300 360
12
10
8
6
4
2
0
%
No. at risk
Clopidogrel Ticagrelor
9,291 9,333
8,521 8,628
8,362 8,460
8,124 6,743 6,743
5,096 5,161
4,047 4,147 8,219
HR 0.84 (95% CI 0.77–0.92)
Clopidogrel
Ticagrelor
p=0.0003
Wallentin L: NEJM 2009; 361:1045-57
CV death, MI or stroke
N=18,624
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Time to major bleeding – primary safety event
No. at risk
Clopidogrel Ticagrelor
9,186 9,235
7,305 7,246
6,930 6,826
6,670
Days from first IP dose
5,209 5,129
3,841 3,783
3,479 3,433
0 60 120 180 240 300 360
10
5
0
15
Clopidogrel
Ticagrelor 11.20 11.58
6,545
HR 1.04 (95% CI 0.95–1.13), p=0.434
K-M
est
imat
ed ra
te (%
per
yea
r)
Wallentin L: NEJM 2009; 361:1045-57
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All patients Ticagrelor (n=6,732)
Clopidogrel (n=6,676) p value*
Dyspnea, %
Any dyspneaç event
Requiring discontinuation of study-
treatment
15.4 0.9
10.4 0.3
<0.0001 < 0.0001
Dyspnea
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Specific P2Y12 Inhibitors: Recommendations
Clopidogrel Prasugrel Ticagrelor Cangrelor
Route Oral Oral Oral IV
Onest 120 – 360 min 60 min 30 min 2 min
Offset 5 days 7 days 5 days 60 min
Reversible No No Yes Yes
Platelet Inhibition
20 – 60% 60 – 80% 70 – 95% 95%
Dosing for PCI LD: 600 mg MD 75 mg
LD 60 mg MD 10 mg
LD 180 mg MD 90 mg BID
LD 3 mcg/kg MD 4 mcg/kg/min
Dosing for Bridging
LD none MD 0.75 mcg/kg/min
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Duration of therapy still unclear?
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Eliano Pio Navarese et al. BMJ 2015;350:bmj.h1618
No significant differences in all cause mortality between short term and 12 month dual antiplatelet therapy
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Longer Duration: DAPT Trial
• 9961 patients • international, multicenter, randomized, placebo-
controlled trial
Mauri LM, et al. NEJM 2014;371:2155-66.
Myocardial infarction that was not related to stent thrombosis (P<0.001) accounted for 55% of the treatment benefit.
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Long DAPT after drug-eluting stent reduced the risks of stent thrombosis and MACE and cerebrovascular events but…
Mauri LM et al NEJM 2014;371:2155-66
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Development and Validation of a Prediction Rule for Benefit and Harm of Dual Antiplatelet Therapy Beyond 1 Year After Percutaneous Coronary
Intervention.
JAMA. 2016;315(16):1735-1749
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Q1 = Score -2 to 0 Q3 = Score Q2 = Score 1 Q4 = Score > 2
JAMA. 2016;315(16):1735-1749
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Optimal DAPT duration after PCI differs according to clinical presentation
GW Stone et al. European Heart Journal (2017) 0, 1–10
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So how do we decide?
Circulation. 2016;133:000–000
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So how do we decide?
Circulation. 2016;133:000–000
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What has really changed?
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European Heart Journal – Cardiovascular Pharmacotherapy (2015) 1, 191–197
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