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Resistance to Anti-Platelet Therapy in CAD. Rabih R. Azar, MD, MSc, FACC Associate Professor of Medicine Director of Cardiovascular Research Division of Cardiology Hotel Dieu de France Hospital. Resistance to Anti-Platelet Therapy in CAD. Role of platelets in coronary artery disease - PowerPoint PPT Presentation
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Resistance to Anti-Platelet Therapy in CADResistance to Anti-Platelet Therapy in CAD
Rabih R. Azar, MD, MSc, FACCRabih R. Azar, MD, MSc, FACC
Associate Professor of MedicineAssociate Professor of Medicine
Director of Cardiovascular ResearchDirector of Cardiovascular Research
Division of CardiologyDivision of Cardiology
Hotel Dieu de France HospitalHotel Dieu de France Hospital
Resistance to Anti-Platelet Therapy in CADResistance to Anti-Platelet Therapy in CAD
1.1. Role of platelets in coronary artery diseaseRole of platelets in coronary artery disease
2.2. Aspirin resistanceAspirin resistance
3.3. Clopidogrel resistanceClopidogrel resistance
4.4. New anti-platelet drugsNew anti-platelet drugs
5.5. How to detect resistance to anti-platelet agentsHow to detect resistance to anti-platelet agents
6.6. How to manage resistant patientsHow to manage resistant patients
Role of the Platelets in ThrombosisRole of the Platelets in ThrombosisRole of the Platelets in ThrombosisRole of the Platelets in Thrombosis
UA/NQMI:Partially-occlusive thrombus
(primarily platelets)
Intra-plaque thrombus (platelet
dominated)
Plaque core
ST MI:occlusive thrombus (platelets,
red blood cells, and fibrin)
Intra-plaque thrombus (platelet dominated)
Plaque core
SUDDEN DEATHAdapted from Davies MJ. Circulation. 1990; 82 (supl II): 30-46.
Aspirin is as important as streptokinase in AMI
ISIS 2: Lancet ISIS 2: Lancet 1988;2:3491988;2:349
Aspirin in Primary and Secondary Prevention TrialsAspirin in Primary and Secondary Prevention Trials
Currently Available Antiplatelet Agents
11Antiplatelet Trialists’ Collaboration. Antiplatelet Trialists’ Collaboration. BMJ.BMJ. 1994;308:81–106. 1994;308:81–106.
22Diener HC et al. Diener HC et al. J Neurol Sci. J Neurol Sci. 1996;143:1–13. 1996;143:1–13. 33Schafer AI. In: Smith TW, ed. Schafer AI. In: Smith TW, ed. Cardiovascular Therapeutics. Cardiovascular Therapeutics. Philadelphia, PA: WB Saunders; 1996:chap 27.Philadelphia, PA: WB Saunders; 1996:chap 27.44Schafer AI. Schafer AI. Am J Med. Am J Med. 1996;101:199–209.1996;101:199–209.
AspirinAspirin
Ticlopidine/Ticlopidine/
clopidogrelclopidogrel
DipyridamoleDipyridamole
MechanismMechanismof Actionof Action
TXATXA22
ADP binding ADP binding to receptorto receptor
cAMPcAMP
EfficacyEfficacy
25%25%11
33%33%11
16%16%22
Significant Significant Side EffectsSide Effects
GI bleeding,GI bleeding,
GI intoleranceGI intolerance33
Severe neutropenia,Severe neutropenia,
rash, diarrhearash, diarrhea44
GI distress, GI distress, headacheheadache44
CAPRIE StudyMI, Ischemic Stroke, or Vascular Death
Months of Follow-UpMonths of Follow-Up
Cu
mu
lati
ve
Ev
en
t R
ate
, %
Cu
mu
lati
ve
Ev
en
t R
ate
, %
00
44
88
1212
1616
00 33 66 99 1212 1515 1818 2121 2424 2727 3030 3333 3636
5.83%5.83%
ClopidogrelClopidogrel
AspirinAspirin
5.33%5.33%
Overall Overall RiskRisk
ReductionReduction
8.7%8.7%
Event Rate per YearEvent Rate per Year
P P = 0.045= 0.045
0.00
0.02
0.04
0.06
0.08
0.10
0.12
0.14
Cum
ula
tive
Haz
ard R
ate
Clopidogrel Clopidogrel + ASA*+ ASA*
33 66 99
Placebo Placebo + ASA*+ ASA*
Months of Follow-UpMonths of Follow-Up
11.4%11.4%
9.3%9.3%
20% RRR20% RRRPP < 0.001 < 0.001
N = 12,562N = 12,562
00 1212
* In combination with standard therapy
The CURE Trial InvestigatorsThe CURE Trial Investigators. N Engl J Med. 2001;345:494-502.
CURE Study: Clopidogrel on the top of aspirinPrimary End Point - MI/Stroke/CV Death
Resistance to Anti-Platelet Therapy in CADResistance to Anti-Platelet Therapy in CAD
1.1. Role of platelets in coronary artery diseaseRole of platelets in coronary artery disease
2.2. Aspirin resistanceAspirin resistance
3.3. Clopidogrel resistanceClopidogrel resistance
4.4. New anti-platelet drugsNew anti-platelet drugs
5.5. How to detect resistance to anti-platelet agentsHow to detect resistance to anti-platelet agents
6.6. How to manage resistant patientsHow to manage resistant patients
Prevalence of ASA Resistance
Gum PA et al. Am J Cardiol 2001;88:230-235
ASA-R: mean aggregation ASA-R: mean aggregation ≥70% with µM 10 ADP & ≥70% with µM 10 ADP & ≥20% with 0.5 mg/ml AA ≥20% with 0.5 mg/ml AA
325 patients with stable CVD taking ASA 325 mg >7days325 patients with stable CVD taking ASA 325 mg >7days
Aspirin Usage In the US
Percentage of Use
37.6
23.3
13.812.2
14.1
0
10%
20%
30%
40%
Heart Disease
Arthritis Headache Body Ache
Other
26,000,000 Americans receive chronic aspirin therapy for
cardioprotection.
26,000,000 Americans receive chronic aspirin therapy for
cardioprotection.
Definitions of Aspirin and Clopidogrel Definitions of Aspirin and Clopidogrel ResistanceResistance
• Clinical:– Failure to prevent clinical events
• Biological:– Failure to adequately inhibit platelet aggregation
– Aspirin:• Aggregation > 70% on 5 µmol/L ADP• Aggregation > 70% on 10 µmol/L ADP• Aggregation > 20% on 0.5mg/mL arachidonic acid
– Clopidogrel:• Baseline – post-treatment ADP aggregation < 10% • ADP aggregation < 14% (Plateletworks)
J Am Coll Cardiol 2006;47:27-33
ASA Resistance and Clinical Outcome in CVD Patients
Gum PA, et al. J Am Coll Cardiol 2003; 41:961-965
ASA-R: mean aggregation ≥70% with 10 µM ADP & ≥20% with 0.5 mg/ml AA
326 CVD patients on ASA 325 mg 326 CVD patients on ASA 325 mg >> 7 days 7 days
p=0.03
Chen et al. J Amer Coll Cardiol 2004;43:1122-6
ASA Resistance in PCI
RPFA-ASA, ASA/clopidogrel (n=151), 19.2% ASA resistant
Possible Mechanisms for Variability in Response to Aspirin
• Decreased bioavailability
– Non-compliance
– Concomitant NSAIDs
• Platelet function
– Accelerated platelet turnover
– Increased platelet COX-2
• Platelet Receptor Polymorphisms
• Other factors
DeGaetano G. J Thromb Haemost 2003;1:2048-50
Metabolic Pathways of Arachidonic Acid
Membrane Phospholipids
ARACHIDONIC ACID
Prostaglandin H2
COX-1
Thromboxane A2 Platelet Aggregation
- Vasoconstriction
Prostacyclin Platelet Aggregation
- Vasodilitation
12-Lipoxygenase
12-HETE, 12-HPETE- Platelet Adhesivity
Non-EnzymaticLipid Peroxidation Catalyzed by Free
Radicals
Isoprostanes- Amplifies platelet response to other agonists. - Vasoconstrictor- Plasma levels 1-2 orders of magnitude > COX -derived metabolites.
Aspirin
Resistance to Anti-Platelet Therapy in CADResistance to Anti-Platelet Therapy in CAD
1.1. Role of platelets in coronary artery diseaseRole of platelets in coronary artery disease
2.2. Aspirin resistanceAspirin resistance
3.3. Clopidogrel resistanceClopidogrel resistance
4.4. New anti-platelet drugsNew anti-platelet drugs
5.5. How to detect resistance to anti-platelet agentsHow to detect resistance to anti-platelet agents
6.6. How to manage resistant patientsHow to manage resistant patients
ACC/AHA Guidelines (2005)ACC/AHA Guidelines (2005)Percutaneous Coronary Interventions: Percutaneous Coronary Interventions:
Oral Antiplatelet TherapyOral Antiplatelet Therapy
Prevalence of inadequate response to Prevalence of inadequate response to clopidogrel 4% to 30%clopidogrel 4% to 30%
Nguyen et al. J Am Coll Cardiol 2005;45:1157-64Nguyen et al. J Am Coll Cardiol 2005;45:1157-64
Adapted from Angiolillo DJ et al. Am J Cardiol. 2006;97:38-43.
Individual Response Variability to Dual Individual Response Variability to Dual AntiplateletAntiplateletTherapy in the Steady State Phase of TreatmentTherapy in the Steady State Phase of Treatment
% % PlateletPlatelet AggregationAggregation (LTA(LTA--ADP 20ADP 20mol/L)mol/L)
97.597.5
92.592.5
87.587.5
82.582.5
77.577.5
72.572.5
67.567.5
62.562.5
57.557.5
52.552.5
47.547.5
42.542.5
37.537.5
32.532.5
27.527.5
22.522.5
17.517.5
12.512.5
7.57.5
2.52.5
2020
1515
1010
55
00
Nu
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f o
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en
tsP
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en
ts
Bleeding riskBleeding risk Ischemic riskIschemic risk
Clinical RelevanceFunctional ParameterN
Post-PCI ischemic events (30 days)
↑ platelet aggregation292Cuisset et al.JACC 2006
Post-PCI ischemic events (30 days)
Post-PCI ischemic events (3 months)
Post-PCI ischemic events (12 months)
↑ platelet aggregation (3rd & 4th quartiles)
↓ platelet inhibition
↑ platelet aggregation
802
379
100
Hocholzer et al.JACC 2006
Geisler et al.Eur Heart J 2006
Bliden et al.JACC 2007
Post PCI-myonecrosis↑ clopidogrel/aspirin-resistant patients120Lev et al.JACC 2006
Post-PCI ischemic events (30 days)
↑ platelet aggregation106Cuisset et al.J Thromb Haemost2006
Myonecrosis and inflammation marker release
↑ periprocedrual platelet aggregation 120Gurbel et al.Circulation 2005
Post-PCI ischemic events(6 months)
↑ periprocedrual platelet aggregation 192Gurbel et al.JACC 2005
Post-primary PCI ischemic events (6 months)
↑ platelet aggregation (4th quartile)60Matezky et al.Circulation 2004
Angiolillo DJ et al. Am J Cardiov Drugs. 2007.
PostPost-- Stent Ischemic Events and Stent Ischemic Events and PeriproceduralPeriprocedural InfarctionInfarction
Clinical Relevance Clinical Relevance of Clopidogrel Nonof Clopidogrel Non--responsivenessresponsiveness
Importance of clopidogrel resistance in ST elevation MI
• Patients with ST elevation MI were divided in 4 quartile according to their response to clopidogrel compared to baseline
• First quartile = Poor responder
• 4th quartile = Excellent responder
• Cardiovascular event rate was higher in the first quartile
Clopidogrel resistance is associated with increased recurrent atherothrombotic events in patient with acute MI
(Circulation 2004;109:3171-3175)
69
58
33
0
10
20
30
40
50
60
70
80
90
100
1st Qtr 2nd Qtr 3rd Qtr 4th Qtr
40
6.7
0 00
5
10
15
20
25
30
35
40
45
1st Qtr 2nd Qtr 3rd Qtr 4th Qtr
% %
Quartiles of mean platelet aggregation Recurrent cardiovascular events
as compared to baseline
Cellular FactorsCellular Factors• Accelerated platelet turnoverAccelerated platelet turnover
•• Reduced CYP3A metabolic activityReduced CYP3A metabolic activity•• Increased ADP exposure Increased ADP exposure •• UpUp--regulation of the P2Yregulation of the P2Y1212 pathwaypathway•• UpUp--regulation of the P2Yregulation of the P2Y11 pathway pathway •• UpUp--regulation of P2Yregulation of P2Y––independent pathwaysindependent pathways
(collagen, epinephrine, TXA(collagen, epinephrine, TXA22, thrombin), thrombin)
Clinical FactorsClinical Factors• Failure to prescribe/poor complianceFailure to prescribe/poor compliance
•• UnderUnder--dosing dosing •• Poor absorptionPoor absorption•• DrugDrug--drug interactions involving CYP3A4drug interactions involving CYP3A4•• Acute coronary syndromeAcute coronary syndrome•• Diabetes mellitus/insulin resistanceDiabetes mellitus/insulin resistance•• Elevated body mass indexElevated body mass index
Genetic FactorsGenetic Factors• Polymorphisms of CYPPolymorphisms of CYP
•• Polymorphisms of Polymorphisms of GPIaGPIa•• Polymorphisms of P2YPolymorphisms of P2Y1212
•• Polymorphisms of Polymorphisms of GPIIIaGPIIIa
Clopidogrel Response VariabilityClopidogrel Response Variability
Angiolillo DJ et al. J Am Coll Cardiol. 2007; 49: 1505-1516 .
Clopidogrel MetabolismClopidogrel Metabolism
• Clopidogrel is a prodrug
• It requires oxidation by the hepatic cytochrome P450 to generate the active metabolite
• Only a small proportion of clopidogrel undergoes metabolism by CYP450
• Clopidogrel is mostly hydrolyzed by esterases to an inactive carboxylic acid derivative that accounts for 85% of clopidogrel-related circulating compounds
• Any drugs that affects CYP450 may affect the efficacy of clopidogrel
Resistance to Anti-Platelet Therapy in CADResistance to Anti-Platelet Therapy in CAD
1.1. Role of platelets in coronary artery diseaseRole of platelets in coronary artery disease
2.2. Aspirin resistanceAspirin resistance
3.3. Clopidogrel resistanceClopidogrel resistance
4.4. New anti-platelet drugsNew anti-platelet drugs
5.5. How to detect resistance to anti-platelet agentsHow to detect resistance to anti-platelet agents
6.6. How to manage resistant patientsHow to manage resistant patients
≈≈ 95% 95% (few minutes)(few minutes)
≈≈ 95% 95% (2(2--4 hours)4 hours)
≈≈ 70% 70% (<1 hour) (<1 hour)
Mean Platelet Mean Platelet InhibitionInhibition
((Time RequiredTime Required))
CHAMPIONCHAMPION
PLATOPLATO
TRITONTRITON
TrialsTrials(Phase III)(Phase III)DoseDoseActionActionRouteRouteTypeTypeDrugDrug
4 4 μμg/kg/ming/kg/minCompetitive Competitive bindingbindingParenteral Parenteral ATP analogue ATP analogue ––
Direct inhibition Direct inhibition CangrelorCangrelor(ARC(ARC--669931MX)669931MX)
90 mg bid90 mg bidCompetitive Competitive bindingbinding
OralOral
CyclopetylCyclopetyl--triazolopytriazolopy--rimidinerimidine ––
Direct inhibitionDirect inhibitionAZD6140AZD6140
60 mg 60 mg loading loading
dose, 10 mg dose, 10 mg maintenance maintenance
dosedose
Irreversible Irreversible bindingbindingOralOral
Thienopyridine Thienopyridine (3(3rdrd gengen) ) ––
requires hepatic requires hepatic conversion to conversion to
active metabolite active metabolite
PrasugrelPrasugrel(CS(CS--747)747)
Novel P2YNovel P2Y1212 ADP Receptor AntagonistADP Receptor Antagonist
More potent and less variability!!More potent and less variability!!
Angiolillo DJ et al. J Am Coll Cardiol. 2007; 49: 1505-1516 .
Adapted from Angiolillo DJ et al. Am J Cardiol. 2006;97:38-43.
Individual Response Variability to Dual Individual Response Variability to Dual AntiplateletAntiplateletTherapy in the Steady State Phase of TreatmentTherapy in the Steady State Phase of Treatment
% % PlateletPlatelet AggregationAggregation (LTA(LTA--ADP 20ADP 20mol/L)mol/L)
97.597.5
92.592.5
87.587.5
82.582.5
77.577.5
72.572.5
67.567.5
62.562.5
57.557.5
52.552.5
47.547.5
42.542.5
37.537.5
32.532.5
27.527.5
22.522.5
17.517.5
12.512.5
7.57.5
2.52.5
2020
1515
1010
55
00
Nu
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Nu
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f o
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ts
Bleeding riskBleeding risk Ischemic riskIschemic risk
Sanofi-aventis-BMS Confidential- For Internal Purposes Only- Not for Further Copying or Distribution
TRITON: Primary Efficacy and Safety Endpoints TRITON: Primary Efficacy and Safety Endpoints in Entire ACS Cohort at 15 Monthsin Entire ACS Cohort at 15 Months
Wiviott SD, et al. N Engl J Med 2007;357:2001-15
0
5
10
15
0 30 60 90 180 270 360 450
Prasugrel
Clopidogrel
Days
En
dp
oin
t (%
)
12.1
9.9
Prasugrel
Clopidogrel1.82.4
CV Death / MI / Stroke
TIMI Major NonCABG Bleeds
HR 0.81(0.73-0.90)
P<0.001
138events
NNT = 46
HR 1.32(1.03-1.68)
P=0.03
35events
NNH = 167
Resistance to Anti-Platelet Therapy in CADResistance to Anti-Platelet Therapy in CAD
1.1. Role of platelets in coronary artery diseaseRole of platelets in coronary artery disease
2.2. Aspirin resistanceAspirin resistance
3.3. Clopidogrel resistanceClopidogrel resistance
4.4. New anti-platelet drugsNew anti-platelet drugs
5.5. How to detect resistance to anti-platelet agentsHow to detect resistance to anti-platelet agents
6.6. How to manage resistant patientsHow to manage resistant patients
How to Measure Platelets Aggregation?
• Platelets function is measured in vitro by light transmission aggregometry
• This method is considered the gold standard
• Disadvantages:
– Limited reproducibility
– Complex sample preparation
– Cannot be routinely performed
WHAT ARE THE ALTERNATIVES WHAT ARE THE ALTERNATIVES TO LIGHT TRANSMISSION TO LIGHT TRANSMISSION
AGGREGOMETRY?AGGREGOMETRY?
Newer Platelet Function Tests
(PFA)-100 Whole blood + Primary Limited range-most ptshemostasis after GP IIb/IIIa inhibitors have
(high shear closure times >300 sec, so may adhes/aggreg) not be able to discern diff. Used
to assay ADP antagonist
Clot Signature Whole blood + Adhesion, Large instrument for routine useAnalyzer aggregation and interpretation of results is
complex
Rapid platelet Whole blood + Aggregation GP IIb/IIa: baseline sample req. function assay Clinical outcome data (GOLD)
Aspirin: AA-like agonist
Harrison P. Br J Hematology 2000;111:733-744Mukherjee D & Moliterno DJ. Clin Pharmacokinet 2000;39(6): 445-458
Flow cytometry Whole blood - Platelet GP, Flexible & powerful. Requires activation markers, specialized operator. ExpensivePlatelet function
AssayAssay Substrate BedsideSubstrate Bedside PrinciplePrinciple Comments Comments
Plateletworks: Kit for measurement of Plateletworks: Kit for measurement of platelets aggregationplatelets aggregation
Photo-optical (turbidometric) platelet Photo-optical (turbidometric) platelet aggregometryaggregometry
Excellent Correlation Between Light Transmission Excellent Correlation Between Light Transmission Aggregometry and Plateletworks Test Aggregometry and Plateletworks Test ((Cathet Cardiovasc Intervent Cathet Cardiovasc Intervent
2001;53:346-351)2001;53:346-351)
PlateletWorks: Values in Healthy Patients*
Agonist % aggregation % inhibtion
Collagen > 70% < 30%
ADP > 86% < 14%
Arach. Acid > 60% < 40%Healthy patients = patients with normal platelets and not on anti-platelet therapy
Resistance to Anti-Platelet Therapy in CADResistance to Anti-Platelet Therapy in CAD
1.1. Role of platelets in coronary artery diseaseRole of platelets in coronary artery disease
2.2. Aspirin resistanceAspirin resistance
3.3. Clopidogrel resistanceClopidogrel resistance
4.4. New anti-platelet drugsNew anti-platelet drugs
5.5. How to detect resistance to anti-platelet agentsHow to detect resistance to anti-platelet agents
6.6. How to manage resistant patientsHow to manage resistant patients
How to Manage Aspirin Resistant Patients
• Assess compliance with treatment
• Eliminate drugs that interfere with aspirin (NSAID)
• Increase the dose of aspirin?– May increase toxicity without improving response
• Add clopidogrel
How to Manage Clopidogrel Resistant Patients
• Assess compliance with treatment
• Eliminate drugs that interfere with the metabolism of clopidogrel (Cytochrome P 450 inhibitors)
• Increase the dose of clopidogrel
*ASA=250-500 mg on admission, then 100 mg/day plus other standard care
Randomized, multicenter, open-label trial with blind centralized laboratory assessment in patients aged 18 85 years with NSTE-ACS (onset < 48 h)
n=35
LMWH and ASA*
Clopidogrel 300 mg LD then 75 mg qd
Clinical follow-upat 30 days
R
Clopidogrel 600 mg LD then 75 mg qd
Clopidogrel 900 mg LD then 75 mg qd
n=34
n=34
D2
D2
D2
0 2 3 4 5 6 2411/2
Sampling Time
Hours post-LD
LD
Variability of response: dose, Variability of response: dose, 300, 600 vs 900300, 600 vs 900
G. Montalescot et al. JACC 2006
P < 0.05 vs. 300 mg LD
A Faster Onset of Action Was Seen with Higher Clopidogrel Loading Regimens
A Faster Onset of Action Was Seen with Higher A Faster Onset of Action Was Seen with Higher ClopidogrelClopidogrel Loading RegimensLoading Regimens
The ALBION trial
0
10
20
30
40
50
1 2 3 4 5 6
300 mg LD600 mg LD900 mg LD
Maximum Inhibition of Platelet Aggregation (5 µM ADP)
Time (h)
(%) Inhibition
Shortened time to reach the highest level of inhibition of the 300 mg LD
Montalescot G et al. J Am Coll Cardiol 2006;48:931-8
Dual Resistance to Aspirin and Clopidogrel in Dual Resistance to Aspirin and Clopidogrel in Patients Undergoing PCIPatients Undergoing PCI
• 150 patients referred for elective PCI
• All were on aspirin 81 to 325 mg/day for > 1 week
• Clopidogrel was given immediately following PCI
• The response to clopidogrel was tested at 24 hours post loading dose
• 12.7% resistant to aspirin
• 24% resistant to clopidogrel
• 47% of aspirin resistant patients were also resistant to clopidogrel
J Am Coll Cardiol 2006;47:27-33
ACC/AHA Guidelines (2005)ACC/AHA Guidelines (2005)Percutaneous Coronary Interventions: Oral Antiplatelet Percutaneous Coronary Interventions: Oral Antiplatelet
TherapyTherapy
CLASS I:CLASS I:
- After the PCI procedure, in patients with neither - After the PCI procedure, in patients with neither aspirin resistanceaspirin resistance, , allergy, nor increased risk of bleeding, aspirin 325 mg daily should be allergy, nor increased risk of bleeding, aspirin 325 mg daily should be given for at least 1 month after BMS implantation, 3 months after given for at least 1 month after BMS implantation, 3 months after sirolimus-eluting stent implantation, and 6 months after paclitaxel-sirolimus-eluting stent implantation, and 6 months after paclitaxel-eluting stent implantation, after which daily chronic aspirin use should eluting stent implantation, after which daily chronic aspirin use should be continued indefinitely at a dose of 75 to 162 mg.be continued indefinitely at a dose of 75 to 162 mg.
CLASS IIb:CLASS IIb:
- In patients in whom subacute thrombosis may be catastrophic or - In patients in whom subacute thrombosis may be catastrophic or lethal, lethal, platelet aggregation studiesplatelet aggregation studies may be considered and the dose of may be considered and the dose of clopidogrel increased to 150 mg per day if less than 50% inhibition of clopidogrel increased to 150 mg per day if less than 50% inhibition of platelet aggregation is demonstrated.platelet aggregation is demonstrated.
Aspirin and Clopidogrel Effects Should Be Aspirin and Clopidogrel Effects Should Be MonitoredMonitored
• 75 year old male
• HTN, treated with ramipril BP: 120/70 mm Hg
• Diabetes, treated with insuline HbA1c: 6.8%
• Hyperlipidemia, treated with atorvastatin LDL: 88 mg/dL
• S/P stent, aspirin and clopidogrel ????????????
Do you want to be sure that aspirin and clopidogrel are working?
Aspirin and Clopidogrel Effects Should Be Aspirin and Clopidogrel Effects Should Be MonitoredMonitored
• 75 year old male
• HTN, treated with ramipril BP: 120/70 mm Hg
• Diabetes, treated with insuline HbA1c: 6.8%
• Hyperlipidemia, treated with atorvastatin LDL: 88 mg/dL
• S/P stent, aspirin and clopidogrel ????????????
Do you want to be sure that aspirin and clopidogrel are working?