Is triple antiplatelet therapy the optimal way forward?

Transcription

Is triple antiplatelet therapy
the optimal way forward?
Sasko Kedev MD, PhD, FESC, FACC
University Clinic of Cardiology Skopje
Macedonia
[email protected]
Triple antiplatelet therapy
in ACS: STEMI/NSTEMI
Sasko Kedev MD, PhD, FESC, FACC
University Clinic of Cardiology Skopje
Macedonia
[email protected]
Progression of Atherosclerosis
Atherothrombosis
Normal
Fatty
Streak
Occlusive
Plaque
Rupture
and
thrombus
formation
Angina
MyocardiaI
Infarction
Sudden
Coronary
Death
Plaque rupture
Time
Platelet activation,
aggregation, and
thrombus formation
Adapted from Libby P. Circulation 2001;104:365-372; Used with Permission. Copyright held by American Heart Association,
see Lippincott Williams & Wilkins www.lww.com; Farb A, et al. Circulation 1996;93:1354-1363
Characteristics of Vulnerable Plaque
Plaque
rupture
♦ Vulnerable plaque
• A thin fibrous cap
Lipid core
• Large lipid-rich core
Thrombus
• High concentration of
inflammatory cells
• Higher probability of plaque
rupture
Fibrous cap
− The cause of the majority
of cardiac events
Platelet Cascade in Thrombosis
Formation
1.) Plaque Rupture,
Release of Platelet
Activators, and Adhesion
Collagen
GP la/lla
la/lla
bind
TXA2
Platelets
GP lb binds von
Willebrand
Factor
Lipid
core
Thrombin
ADP
2.) Platelet Activation
5HT
Lipid
core
Activated
GP llb/llla
3.) Platelet Aggregation
ADP=Adenosine diphosphate; 5HT=5-hydroxytryptamine;
TXA2=Thromboxane 2
Fibrinogen
Lipid
core
Adapted from Schafer AI. Am J Med. 1996;101:199-209
Platelet Activation Pathways
5HT
Thromboxane A2
5HT
ADP
Collagen
ADP
ADP
Coagulation
TPα
Thrombin
GPV1
5HT2A
Par4
ATP
ATP
P2Y1
P2X1
Par1
Platelet
Activation
Thrombin
generation
Dense
granule
P2Y12
Shape change
Alpha
granule
Amplificati
on
αIIbβ3
Coagulation factors
Inflammatory mediators
αIIbβ3
P2Y12 is critical
for
amplification
Aggregation
αIIbβ3
Fibrinogen
Adapted from Storey RF. Curr Pharm Des 2006;12:1255-1259
Platelet Adhesion and Aggregation
Under HighHigh-shear Flow
Flowing
disc-shaped,
dormant
platelet
Rolling
ball-shaped
platelet
Activated, aggregating platelets
illustrating fibrin strands
Hemisphere-shaped
platelet
Reversible Adhesion
Spreading
platelets
Irreversible Adhesion
Antiplatelet Therapy: Targets
Clopidogrel bisulfate
Ticlopidine hydrochloride
Prasugrel hydrochloride
Dipyridamole
Phosphodiesterase
ADP
ADP
Gp 2b/3a Inhibitors
Gp IIb/IIIa
(Fibrinogen
Receptor)
Activation
COX
Collagen
Thrombin
TXA2
TXA2
Aspirin
ADP=Adenosine diphosphate, COX=Cyclooxygenase, TXA2=Thromboxane A2
Source: Schafer AI. Antiplatelet Therapy. Am J Med 1996;101:199–209.
Acute Coronary Syndromes
ACS: Plaque rupture with superimposed thrombosis
and partial or total occlusion of an artery
No ST Elevation
ST Elevation
(STEMI)
Unstable NSTEMI
Angina
ACS=Acute coronary syndromes; NSTEMI=Non–ST-elevation
myocardial infarction; STEMI=ST-elevation myocardial infarction
Adapted from Alpert JS et al. J Amer Coll Cardiol 2000;36:959-969
Coronary Heart Disease
Acute Coronary Syndromes
Stable Angina
UA/NSTEMI
STEMI
Continuum of Severity
JJ
Adapted from Cannon CP. J Thrombolysis 1995:2:205-218
ECG Changes in ACS
T-Wave Inversion
• UA/NSTEMI
ST-T Depression
• UA/NSTEMI
ST-T Elevation
• STEMI
ACS=Acute coronary syndromes; UA=Unstable angina; NSTEMI=Non–ST-elevation myocardial infarction; STEMI=STelevation myocardial infarction
Diagnostic Coronary Angiography
Aorta
♦ Radiographic visualization
of the coronary vessels after
injection of radiopaque
contrast media
Aortic
valve
♦ Defines coronary anatomy
and degree of luminal
obstruction
♦ Assesses feasibility of
revascularization
♦ Confirms coronary disease
when diagnosis is uncertain
and cannot be reasonably
excluded by noninvasive
techniques
Right
coronary
artery
Catheter
entrance
Catheter
Coronary Angiography
- Sub occlusion LAD, TIMI 2 Flow
- Tight Stenosis OM1
- Occlusion RCA
- No Refractory Angina
Syntax score 26
Euroscore 3%
Percutaneous Transluminal Coronary
Angioplasty (PTCA)
Balloon is
expanded
several
times
Coronary artery occlusion
site
A balloon-tipped
catheter is
inserted in
coronary artery
Percutaneous Coronary Intervention
(PCI) With Stent
Stent
Vessel wall
Plaque
Catheter
Balloon
Expanded Stent
PCI of LAD
DES 2.75-28, 18 atm
Radial Access, EBU 4.5 Guiding 6F, 0.014 BMW Wire
PCI of Cx
DES 3.5-18, 18 atm
Radial Access, EBU 4.5 Guiding 6F, 0.014 BMW Wire
Coronary Artery Bypass Graft (CABG)
Radial artery
bypass
Internal mammary
artery bypass
Saphenous vein bypass
Sites of occlusion
Incidence of STEMI and NSTEMI
American Journal of Medicine 2011; 124:40-47
Mortality rates for STEMI and NSTEMI
American Journal of Medicine 2011; 124:40-47
Baseline Ischemia Risk Assessment and
Bleeding Risk
Armstrong, P. W. et al. J Am Coll Cardiol Intv 2010;3:1178-1180
Post-Procedural Bleeding and 1-Year Mortality
Ndrepepa, G. et al. J Am Coll Cardiol 2008;51:690-697
Less Bleeding Is Associated With Improved
Survival
OASIS-5
Lower bleeding in fondaparinux group vs enoxaparin group :
2.2% vs 4.1%; HR, 0.52 (95%Cl, 0.44-0.61)
Lower mortality in fondaparinux group: 6,5% vs 5,8% (P = .05)
HORIZONS-AMI
Lower bleeding in bivalirudin group vs UFH/GP IIb/IIIa
inhibitors: 4,9% vs 8,3%, P < .001
Lower cardiac-related mortality in bivalirudin group persisted
at 1 year (2.1% vs 3,8%; HR, 0.57 [95%Cl, 0.38-0.84], P=.005)
Bleeding is Associated With Death and
ischemic Events
Eikelboom JW, et al.Circulation. 2006;114:774-782.
The Spectrum of Coronary Artery Disease:
Matching Therapy with Pathophysiology
Increasing risk of thrombotic event
General
prevention
Symptomfree phase
High-risk
Stable
angina
Acute coronary
syndromes
Control Risk Factors
Diet
Exercise
Smoking cessation
+
Preventive Therapy
Aspirin +
Statin +
ACE inhibitor
+
Anti-ischemic Therapy
Nitroglycerin +
Beta-blockers +
Calcium channel blockers
Reperfusion Therapy
Percutaneous coronary
intervention or coronary
artery bypass graft
Adapted from Libby P et al. Circulation 2005;111:3481-3488;
Antman EM, et al. J Am Coll Cardiol 2004;44:E1-E211
+
Anti-thrombotic Therapy
Fibrinolytics (STEMI)
Heparins
Aspirin + clopidogrel
GPIIb/IIIa antagonist
Direct thrombin inhibitor
Factor Xa inhibitor
Pharmacological Treatment during PPCI
Antithrombotic therapy:
UFH / LMWH
Bivalirudin
Antiplatelet therapy:
ASA
Clopidogrel / Prasugrel / Ticagrelor
GP IIb/IIIa antagonists
27
Glycoprotein llb/llla Receptor Antagonists
28
TACTICS –TIMI 18
TACTICS –TIMI 18
HDB Tirofiban studies
in ACS PCI
ADVANCE
EVEREST
TRIPAS
STRATEGY
MULTI STRATEGY
DANZI
FATA
ON TIME 2
ADVANCE: Study Design
• Single-center, double-blind, placebo-controlled, randomized
• Patients with high-risk features undergoing elective/urgent
PCI
• non–ST-segment elevation ACS or
• diabetes mellitus and at least one coronary stenting or
• planned multivessel intervention (stenting of 2 lesions of least
70% coronary stenosis in different coronary vessels
Thienopyridine, ASA, and UFH
(500 mg ticlopidine/300 mg clopidogrel loading dose)
HDB Tirofiban
Placebo
25-µg/kg, bolus, 0.15-µg/kg infusion
(n=101)
(n=101)
Endpoints
• Primary: Death/NFMI/uTVR /GP IIb/IIIa bailout at 180 days
• Secondary: Effect on TnI levels; ± diabetes
Adapted from Valgimigli M, et al. J Am Coll Cardiol. 2004;44(1):14-19.
ADVANCE: Primary Endpoint at 6 Months
P=.048
% of Patients
P=.01
P=.29
P=.052
P=.60
Primary
Endpoint
MACE*
Death
*Death, MI, or TVR
MI
TVR
ADVANCE: Troponin I and CK-MB
ng/mL
P<.01
P=.001
Troponin I
CK-MB
ADVANCE: Safety
•
•
•
•
No incidence of major
bleeding
No RBC transfusions
No severe
thrombocytopenia
One mild thrombocytopenia
in each group
ADVANCE: Conclusion
• In at-risk patients undergoing PCI, HDB tirofiban + infusion
w/heparin compared with heparin alone significantly reduced:
– MACE (death, MI, or TVR)
– The Primary endpoint (death, MI, TVR, or thrombotic bailout)
• In subgroup analysis, patients who were diabetic or patients with
ACS significantly benefited from the addition of HDB tirofiban
• HDB tirofiban + infusion significantly reduced post-PCI elevations in
TnI or CK-MB as compared with heparin alone
• There were no major bleeds, RBC transfusions, or severe
thrombocytopenia in either group
EVEREST: Study Design
• Angina at rest within 12 h of
admission
• Unequivocal changes on
ECG during angina
• cTnI elevation
“In-Lab”
Abciximab
ASA/heparin
thienopyridine
High-risk
NSTEMI
ACS
“In-Lab”
HDB Tirofiban
“Upstream”
Tirofiban
ASA/heparin
thienopyridine
ASA/heparin
thienopyridine
tirofiban
Intent to PTCA/stent
24 - 48 hours
24 - 48 hours
24 - 48 hours
+ Abciximab
+ HDB tirofiban
Adapted from Bolognese L, et al. J Am Coll Cardiol. 2006;47(3):522-528.
EVEREST: Primary Endpoints
• Tissue-level perfusion based on:
– Corrected TIMI Frame Count (cTFC)
– TIMI Myocardial Perfusion Grade (TMPG)
– Intracoronary myocardial contrast echocardiography (MCE) before
and immediately after PCI and after cardiac troponin I (cTnI)
EVEREST: Tissue-Level Perfusion by
TMPG Pre- and Post-PCI
Pre-PCI
Post-PCI
n=93
P=.015
TMPG 0/1 (%)
TMPG 0/1 (%)
P=.0009
Upstream
Tirofiban
HDB
Abciximab
Tirofiban
Upstream
Tirofiban
HDB
Tirofiban
Abciximab
EVEREST: Tissue-Level Perfusion by
Myocardial Contrast Echocardiography (MCE)
MCE score index
n=93
Normal tissue-level
perfusion by MCE
P=.04
MCE Score Index
Patients Perfused (%)
P=.012
Upstream HBD Abciximab
Tirofiban Tirofiban
Upstream
HBD Abciximab
Tirofiban Tirofiban
EVEREST: Peak cTnI Levels Post-PCI
n=93
P=.0002
ng/mL
P=.015
Upstream
Tirofiban
HBD
Tirofiban
Abciximab
EVEREST: Conclusion
• In patients with high-risk NSTEMI ACS:
– HDB tirofiban (25 µg/kg bolus for 3 min followed by 0.15 µg/kg/min
infusion) initiated in-lab is similar to in-lab abciximab with regard to
various measures of myocardial perfusion
– Tirofiban (0.4 µ g/kg/min X 30 min followed by 0.1 µg/kg/min
infusion) initiated upstream is significantly better to in-lab
abciximab with regard to various measures of myocardial perfusion
– Tirofiban (0.4 µg/kg/min X 30 min followed by 0.1 µg/kg/min
infusion) initiated upstream is significantly better to both in-lab HDB
tirofiban and in-lab abciximab with regard to reducing peak cTnI
levels post-PCI
MULTISTRATEGY: Study Design
STEMI “all-comer” patients
•Aspirin + clopidogrel + UFH before arterial sheath insertion
•Coronary angiography ± PCI
•Stenting was the default strategy in patients with
RVD ≥2.5 mm at visual estimation
1:1
HDB Tirofiban*
Abciximab
1:1
1:1
SES
BMS
SES
BMS
*Given as a bolus of 25 µg/kg, followed by an 18- to 24-hour infusion at 0.15 µg/kg/min.
Clinical follow-up at 1, 4, and 8 months; 1 to 5 years
Adapted from Valgimigli M, et al. JAMA. 2008;299(15):1788-1799.
MULTISTRATEGY: Primary Endpoints
• Pharmacology Arm
Noninferiority basis
– ≥50% Σ ST-segment elevation resolution within 90 min after
last balloon inflation @ tt-EKG
• Stent Arm
Superiority basis
– Cumulative rate of MACE, defined as overall death,
reinfarction, or TVR within 8 months
MULTISTRATEGY: Primary Endpoint
% of Patients
P<.001 noninferiority
P=.53 superiority
H0: 85%
n=361
n=361
Abciximab
HDB Tirofiban
MULTISTRATEGY: 8-Month Outcomes
MACE (death, reinfarction, and TVR)
% of Patients
P=.004
n=372
Bare Metal Stent
n=372
Sirolimus Stent
MULTISTRATEGY: 8-Month Outcomes
MACE (death, reinfarction, and TVR)
% of Patients
P=.30
n=372
Abciximab
n=372
HDB Tirofiban
MULTISTRATEGY: Conclusion
• In STEMI patients managed with primary PCI with stenting HDB
tirofiban compared with abciximab:
– Is non-inferior in reducing ST-segment resolution 90 minutes postprocedure
– Demonstrated no significant difference in:
• MACE (death, reinfarction, or TVR) at 30 days and at 8 months
• TIMI major or TIMI minor bleeding
• The rate of late stent thrombosis
• Use of SES significantly reduced MACE at 8 months
– Primarily driven by a significant reduction in TVR
• There were significant increase in severe and any thrombocytopenia in
patients administered abciximab compared with HDB tirofiban
On-TIME 2: Study Design
STEMI
diagnosed in ambulance or
referral center
ASA + 600 mg clopidogrel + UFH
Placebo
N=984
Jun 2006–Nov 2007
HDB Tirofiban*
Transportation
Angiogram
PCI center
Angiogram
Provisional
HDB Tirofiban
PCI
Tirofiban
cont’d
*Bolus: 25 µg/kg and 0.15 µg/kg/min infusion.
Adapted from van ‘t Hof AWJ, et al. Lancet 2008;16;372(9638):537-46
On-TIME 2: Endpoints
Primary:
• Residual ST segment deviation (>3 mm) 1 hour after PCI
Key Secondary:
• Combined occurrence of death, recurrent MI, urgent TVR,
or thrombotic bailout at 30 days follow-up
• Safety (major bleeding)
On-TIME 2: ST-Segment >3 mm Deviation
1 Hour Post-PCI
% of Patients
P=.02
n=493
n=491
Placebo
HDB Tirofiban
On-TIME 2: Outcomes at 30 Days
On-TIME 2: Mortality at 1 Year
Primary PCI Subgroup
Adapted from presentation by Christen Hamm, MD, Kerckhoff Heart Center, Bad Nauheim,
Germany, at the American College of Cardiology (ACC) Annual Scientific Sessions, March 2009.
HDB Tirofiban in Primary PCI: Conclusion
• MULTISTRATEGY demonstrated that HDB tirofiban is as safe
and effective as Abciximab in patients with STEMI undergoing
primary PCI w/stenting at 30 days and at 8 months
– With significantly lower rates of thrombocytopenia at 30 days
• On-TIME 2 demonstrated the efficacy and safety of pre-hospital
administration of HDB tirofiban in patients with STEMI
w/planned primary PCI at 30 day
– With significant reductions in all-cause and cardiac mortality in the cohort
of patients undergoing primary PCI at 1 year
www.escardio.org/guidelines
Revascularization in NSTEMI Antithrombotic pharmacotherapy
European Heart Journal (2010) 31, 2501–2555
Revascularization in NSTEMI Antithrombotic pharmacotherapy
GPIIb–IIIa inhibitors should be used in patients with
high ischaemic risk undergoing PCI.
The greatest benefit of GPIIb–IIIa inhibitors vs.
placebo was demonstrated in earlier RCTs when
ADP receptor blockers were not routinely used.
The selective ‘downstream administration’ of
abciximab in the catheterization laboratory, in
combination with a 600 mg clopidogrel loading dose,
has been shown to be effective in troponin-positive
NSTE-ACS patients and might therefore be preferred
over upstream use.
Randomized trials of GP llb/llla inhibitors
(dark bars) VS control (open bars)
Recommendations for GP IIb/IIA Inhibitors (1)
In patients at intermediate to high risk, particularly
patients with elevated troponins, ST-depression, or diabetes, either
eptifibatide or tirofiban for initial early treatment are recommended in
addition to oral antiplatelet agents. (II-A)
The choice of combination of antiplatelet agents and
anticoagulants should be made in relation to risk of
ischaemic and bleeding events. (I-B)
Patients who received initial treatment with eptifibatide or
tirofiban prior to angiography, should be maintained on
the same drug during and after PCI. (Ila-B)
Recommendations for GP IIb/IIIA Inhibitors (2)
In high risk patients not pretreated with GP Ilb/IIIa inhibitors and
proceeding to PCI, abciximab is recommended immediately
following angiography. (I-A) The use of eptifibatide or tirofiban in
this setting is less well established. (IIa-B)
GP IIb/IIIa inhibitors must be combined with an anticoagulant. (I-A)
Bivalirudin may be used as an alternative to GP IIb/IIIa inhibitors
plus UFH/LMWH. (IIa-B)
When anatomy is known and PCI planned to be performed with in
24 hours with GP IIb/IIIa inhibitors, most secure evidence is for
abciximab (IIa-B)
Treatment Effect on 30-day Mortality Among Diabetic Patients
with NSTE ACS from Six Randomized Clinical Trials
ESC Guidelines for the Management of NSTE –ACS(112)
Recommendations for Diabetes
Tight glycaemic control to achieve normoglycaemia as soon as possible is
recommended in all diabetic patients with NSTE-ACS in the acute phase. (I-C)
Insulin infusion may be needed to achieve normoglycaemia in selected NSTEACS patients with high blood glucose levels at admission. (lla-C)
Early invasive strategy is recommended for diabetic patients with NSTE-ACS. (l-A)
Diabetic patients with NSTE-ACS should receive intravenous GP llb/llla inhibitors
as part of the initial medical management which should be continued through
the completion of PCI. (lla-B)
ESC Guidelines for the Management of NSTE –ACS(113)
2011 ACCF/AHA Focused Update of the
Guidelines for the Management of Patients With
Unstable Angina/Non ST-Elevation Myocardial
Infarction (Updating the 2007 Guideline)
J. Am. Coll. Cardiol. published online Mar 28, 2011; doi:10.1016/j.jacc.2011.02.009
Guidelines for NSTEMI
Patients with definite UA/NSTEMI at medium or high risk
and in whom an initial invasive strategy is selected should
receive dual-antiplatelet therapy on presentation.
(Level of Evidence: A)
ASA should be initiated on presentation. (Level: A)
The choice of a second antiplatelet therapy to be added
to ASA on presentation includes 1 of the following:
2011 ACCF/AHA UA/NSTEMI Guideline Update
EARLY and ACUITY support selective rather than
Provisional GP llb/llla
No upstream GP llb/llla use in low-risk patients
Early conservative strategy:Enoxaparin or
fondaparinux preferred over GP llb/llla inhibitors (Class
lla.LOE:B)
No planned PCI
No abciximab (Class lll,LOE:A)
Invasive strategy: As second antiplatelet agent, IV
eptifibatide or tirofiban preferred prior to angiography.
Guidelines for NSTEMI
Before PCI:
● Clopidogrel (Level: B); or
● An IV GP IIb/IIIa inhibitor. (Level: A)
IV eptifibatide or tirofiban are the preferred
GP IIb/IIIa inhibitors.
At the time of PCI:
● Clopidogrel if not started before PCI (Level: A); or
● Prasugrel (Level: B); or
● An IV GP IIb/IIIa inhibitor. (Level: A)
Use of Glycoprotein IIb/IIIa Receptor
Antagonists in STEMI
Modified
Recommendation
I IIa llb III
It is reasonable to start treatment with
glycoprotein IIb/IIIa receptor antagonists at the
time of primary PCI (with or without stenting) in
selected patients with STEMI:
abciximab
I IIa llb III
tirofiban and eptifibatide
Use of Glycoprotein IIb/IIIa Receptor
Antagonists in STEMI
Modified
Recommendation
I IIa llb III
The usefulness of glycoprotein IIb/IIIa receptor
antagonists (as part of a preparatory
pharmacologic strategy for patients with STEMI
prior to arrival in the cardiac catheterization
laboratory for angiography and PCI) is
uncertain.
Primary PCI
I
I
STEMI patients presenting to a hospital
with PCI capability should be treated with
primary PCI within 90 min of first medical
contact as a systems goal.
STEMI patients presenting to a hospital without
PCI capability, and who cannot be transferred to a
PCI center and undergo PCI within 90 min of
first medical contact, should be treated with
fibrinolytic therapy within 30 min of hospital
presentation as a systems goal, unless fibrinolytic
therapy is contraindicated.
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
If there is a delay to the Cath Lab,
should one give lytics to facilitate
reperfusion prior to PCI ?
FINESSE Trial:
All-Cause Mortality Through 1 Year
Ellis, S. G. et al. J Am Coll Cardiol Intv 2009;2:909-916
FINESSE Trial:
Primary End Point in High-Risk Subgroup
Herrmann, H. C. et al. J Am Coll Cardiol Intv 2009;2:917-924
CARESS-IN-AMI: Primary Outcome
primary outcome (composite of all cause mortality, reinfarction, & refractory MI within
30 days)
occurred significantly less often in the immediate PCI group vs. standard care/rescue
PCI group
10.7%
4.4%
HR=0.40 (0.21-0.76)
Di Mario et al. Lancet 2008;371:559
Reperfusion Strategies following fibrinolysis
Primary Endpoint : 30 Day Death, re-MI,CHF.
Severe Recurrent ischaemia, Shock
Cantor et al. N Engl J Med 2009;360:26.
TRITON TIMI-38 STEMI Cohort n=3534
15
CV Death / MI / Stroke
Clopidogr
el
12.4
%
9.5
%
Percent (%)
10
10.0
%
HR
6.5
%
HR
0.68
(0.54P=0.00
0.87)
2
5
(0.650.79
P=0.0
0.97)
NNT
2 = 42
Prasugre
l
TIMI Major
NonCABG Bleeds
2.4
Prasugre
l
Clopidogr
el
2.1
0
0
30
60
90
Montalescot et al Lancet 2008.
18
0
27
0
Days From Randomization
36
0
45
0
Antiplatelet Agents Shown to Reduce Stent
Thrombosis
Dixon, S. R. et al. J Am Coll Cardiol 2010;55:2272-2286
Tailoring Treatment with Tirofiban in pts
showing Resistance to Aspirin and/or
Clopidogrel (3T/2R)
Valgimigli M et al. Circulation 2009;119:3215-3222
Rates of periprocedural MI according to the
primary end-point definition
Rates of periprocedural myocardial damage according to multiples of the
upper limit of reference value in at least 1 (A and C) or 2 (B and D)
consecutive sample(s) for either troponin I or T (A and B) and CK-MB (C and
D)
Logarithmic (log) risk ratios and rates of
the primary end point
Why Radial or Ulnar
Artery Access
for Post Thrombolysis
PCI ?
Impact of Therapies on Outcomes
Ischemic events:
MI/CKMB↑
Stent Thrombosis
Bleeding
Post-Procedural Bleeding and 1-Year Mortality
Ndrepepa, G. et al. J Am Coll Cardiol 2008;51:690-697
Meta-analysis: Radial vs Femoral Access
RRR 29%
P=0.21
5
4.5
RRR 29%
P =0.058
4
23 random. trials
7.020 patients
3.5
3
RRR 73%
P < .001
RRR 26%
P =0.29
2.5
Radial
2
1.5
1
0.5
0
Major
Bleed
Death/MI
CVA
Death
Jolly et al. Am Heart J 2009
Fail to cross
Lesion W/B
Femoral
Bleeding and Vascular Complications of R-PCI and
F-PCI in Key Subgroups
Rao SV et al. J Am Coll Cardiol Intv 2008; 1:379-386
RIVAL Study Design
NSTE-ACS and STEMI
(n=7021)
Key Inclusion:
•Intact dual circulation of hand required
•Interventionalist experienced with both
(minimum 50 radial procedures in last year)
Randomization
UA (%) 44.3
NSTEMI (%) 28.5
STEMI (%) 27.2
Radial Access
(n=3507)
Femoral Access
(n=3514)
UA (%)
NSTEMI (%)
STEMI (%)
Primary Outcome: Death, MI, stroke
or non-CABG-related Major Bleeding at 30 days
Jolly SS et al. Lancet 2011;377:1409-20
45.7
25.8
28.5
RIVAL: Therapies at Initial Hospitalization
RIVAL: Sites of Non-CABG Major Bleeds
RIVAL: STEMI vs NSTE-ACS
Immediate PCI after successful TT
Case 4.
Case 5.
49 y.o. male: 1h from chest pain
49 y.o. male: FMC to BT – 2 h
LM 100%
PCI wire in LAD
DES 3.5/24 x 18
Final result
Conclusions
Weight risks for individual patients: Triple therapy vs DAPT
Patients undergoing PCI: Aggressive APT reduces stent
thrombosis rate
Balance between bleeding and ischemia/thrombosis risk
Triple therapy in pts with high ischemia risk and high
thrombotic burden undergoing PCI
More trial results to come
The Future -Expectations
New Agents:
Ticagrelor(P2Y12)
Dabigatran
Vorapaxar, Atopaxar (PAR - 1)
Higher risk patients
Elderly
Acute ACS
Radial Approach
Tailored combination
therapy to balance
thrombotic and bleeding risks
Take home points
Platelet inhibition is fundamental to PCI success
- not only long-term, but also short-term.
The benefit of GP2b3a receptor blockade is
greatest in high-risk patients.
Timing remains important, but the emphasis
should be on reducing time to PCI in all ACS.
Determining the balance of thrombosis risk and
bleeding complications requires careful thought.

Is triple antiplatelet therapy the optimal way forward?

Transcription

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