Welcome
Cara Bilinsky
ACCELMED
Logistical Information
Track Number:
• Track 1 = Red travel packet
• Track 2 = Blue travel packet
Departure:
• Departure city = city on ID
Rotation:
• You will rotate sessions every 25 minutes
• 5-minute transition time between sessions
Logistical Information (cont’d)
Passport:
• Refer to your passport for the program slides,
faculty bios, and credit information
Brochures:
• 3 sessions have handouts for additional
information
Stations:
• Please stay with your assigned travel group
• After the 3 sessions, we will reconvene for the
conclusion
Logistical Information (cont’d)
Pre/Postsurvey:
• Located in the center of your travel packet
• Complete the presurvey prior to the first session
• After the last session, complete the postsurvey
Evaluation Form:
• Located in the center of your travel packet
• Turn in at the registration tables as you leave
Credit:
• Complete the information on the Evaluation Form,
and your certificate will be issued by mail
Welcome and Overview
Deepak L. Bhatt, MD, MPH, FACC, FAHA, FSCAI, FESC
Professor of Medicine, Harvard Medical School
Chief of Cardiology, VA Boston Healthcare System
Director, Integrated Interventional Cardiovascular Program
Brigham and Women's Hospital and VA Boston Healthcare System
Senior Investigator, TIMI Study Group
Boston, Massachusetts
Accreditation and Funding
Jointly sponsored by the Postgraduate Institute for Medicine (PIM) and
ACCELMED.
This activity is supported by an educational grant from Daiichi Sankyo, CO.,
LTD., and Lilly USA, LLC.
This educational activity may contain discussion of published and/or
investigational uses of agents that are not indicated by the FDA. PIM,
ACCELMED, Daiichi Sankyo CO., LTD., and Lilly USA, LLC do not
recommend the use of any agent outside of the labeled indications.
The opinions expressed in the educational activity are those of the
faculty and do not necessarily represent the views of PIM, ACCELMED,
Daiichi Sankyo CO., LTD. and Lilly USA, LLC. Please refer to the
official prescribing information for each product for discussion of
approved indications, contraindications, and warnings.
Accreditation and Funding (cont’d)
Physician Continuing Medical Education
Accreditation Statement
This activity has been planned and implemented in accordance with the
Essential Areas and policies of the Accreditation Council for Continuing Medical
Education through the joint sponsorship of Postgraduate Institute for Medicine
and ACCELMED. The Postgraduate Institute for Medicine is accredited by the
ACCME to provide continuing medical education for physicians.
Credit Designation
The Postgraduate Institute for Medicine designates this live activity for a
maximum of 2.0 AMA PRA Category 1 Credit(s)™. Physicians should claim
only the credit commensurate with the extent of their participation in the activity.
Faculty Disclosures
The faculty reported the following financial relationships or relationships to
products or devices they or their spouse/life partner have with commercial
interests related to the content of this CME activity:
Name of Faculty/Presenter
Deepak L. Bhatt, MD, MPH, FACC, FAHA,
FSCAI, FESC
Activity Chair
Reported Financial Relationship
Contracted Research: Amarin Corp.; AstraZeneca; Bristol-Myers Squibb
Company; Eisai, Inc.; Ethicon, Inc.; Medtronic; sanofi-aventis; The Medicines
Company
Dominick J. Angiolillo, MD, PhD, FACC, FESC, Consulting Fees: Abbott Vascular; Accumetrics; Arena Pharmaceuticals, Inc.;
FSCAI
AstraZeneca; Bristol-Myers Squibb Company/sanofi-aventis; Daiichi Sankyo,
CO., LTD./Lilly USA, LLC; Evolva; Medicure, Inc.; Merck & Co., Inc.; Novartis
International AG; Portola Pharmaceuticals, Inc.; The Medicines Company
Contracted Research: Boston Scientific; Bristol-Myers Squibb
Company/sanofi-aventis; Daiichi Sankyo, CO., LTD./Lilly USA, LLC;
GlaxoSmithKline; Otsuka America, Inc.
Speakers’ Bureaus: Abbott Vascular; AstraZeneca; Bristol-Myers Squibb
Company/sanofi-aventis; Daiichi Sankyo, CO., LTD./Lilly USA, LLC
Faculty Disclosures (cont’d)
Name of Faculty/Presenter
Reported Financial Relationship
Paul A. Gurbel, MD
Consulting Fees: Accumetrics; AstraZeneca; Bayer Healthcare Pharmaceuticals;
Boehringer Ingelheim GmbH; CSL Limited; Daiichi Sankyo, CO., LTD./Lilly USA,
LLC; Iverson Genetics Diagnostics, Inc.; Haemonetics Corporation; Medtronic;
Merck & Co., Inc.; Nanosphere, Inc.; Novartis International AG; POZEN, Inc.;
sanofi-aventis
Patents: Personalized antiplatelet therapy and interventional cardiology
Contracted Research: AstraZeneca; CSL Limited; Daiichi Sankyo, CO.,
LTD./Lilly USA, LLC; Duke Clinical Research Institute; Haemoscope; Harvard;
Medtronic; National Institutes of Health; POZEN, Inc.; sanofi-aventis
Speakers’ Bureaus: Daiichi Sankyo, CO., LTD./Lilly USA, LLC; Iverson Genetics
Diagnostics, Inc.; Merck & Co., Inc.; Nanosphere, Inc.; sanofi-aventis
Gilles Montalescot, MD, PhD
Consulting Fees: Abbott Vascular; AstraZeneca; Bayer Healthcare
Pharmaceuticals; Biotronik; Boehringer Ingelheim GmbH; Daiichi Sankyo, CO.,
LTD.; GlaxoSmithKline; Lilly USA, LLC; Iroko Pharmaceuticals, LLC; The
Menarini Group; MSD India; Nanosphere, Inc.; Novartis International AG; Pfizer,
Inc.; Portola Pharmaceuticals, Inc.; Roche Diagnostics; sanofi-aventis; The
Medicines Company
Contracted Research: AstraZeneca; Biotronik; Bristol-Myers Squibb Company;
Boston Scientific; Brahms; Daiichi Sankyo, CO., LTD; GlaxoSmithKline; Lilly USA,
LLC; Medtronic; Nanosphere, Inc.; Pfizer, Inc.; Roche Diagnostics; sanofi-aventis;
Spartan Bioscience, Inc.; Stago; STENTYS SA
Faculty Disclosures (cont’d)
Name of Faculty/Presenter
Reported Financial Relationship
E. Magnus Ohman, MD, FRCPI, FESC, FACC,
FSCAI
Consulting Fees: AstraZeneca; Boehringer Ingelheim GmbH; Bristol-Myers
Squibb Company; Gilead Sciences, Inc.; Janssen Global Services, LLC.;
LipoScience, Inc.; Merck & Co., Inc.; POZEN, Inc.; Roche Diagnostics; sanofiaventis; The Medicines Company; WebMD
Contracted Research: Daiichi Sankyo, CO., LTD./Lilly USA, LLC
P. Gabriel Steg, MD
Consulting Fees: Amarin Corp.; Astellas; AstraZeneca; Bayer Healthcare
Pharmaceuticals; Boehringer Ingelheim GmbH; Bristol-Myers Squibb
Company/sanofi-aventis; Daiichi Sankyo, CO., LTD./Lilly USA, LLC;
GlaxoSmithKline; Iroko Pharmaceuticals, LLC; Medtronic; MSD India; Novartis
International AG; Otsuka America, Inc.; Pfizer, Inc.; Roche Diagnostics; sanofiaventis; Servier; The Medicines Company
Contracted Research: NYU School of Medicine; sanofi-aventis; Servier
Ownership Interest: Aterovax
Learning Objectives
After completing this activity, the participant should be better able to:
1. Incorporate antiplatelet therapies at an optimal dose to maximize
benefit and minimize adverse events in the treatment of patients
with ACS
2. Evaluate the role of genetic testing and potential drug-drug
interactions on the choice of antiplatelet therapy
3. Appraise the current evidence on platelet function testing in
choosing or altering antiplatelet therapy appropriately in patients
Agenda
Please join us in your assigned track.
2000
1500
1000
500
0
ACS
MI
UA
Incidence Rate
(# of cases/100,000 person-yr)
Number of Hospitalizations
(x 1000)
Trend in Hospitalizations for ACS, MI, and UA
Age- and Sex-adjusted Incidence
Rates of AMI, 1999-2008
300
250
][
][
][
][
200
150
100
50
][
][
][
][
][
][
][
][
][
][
][
][
][
][
][
][
][
MI
][
][ ][
][
NSTEMI
STEMI
][ ][ ][
][
][
0
ACS = acute coronary syndromes. AMI = acute myocardial infarction. MI = myocardial infarction. NSTEMI = non-ST elevation myocardial infarction. STEMI = ST elevation
myocardial infarction. UA = unstable angina.
Error bars represent 95% confidence intervals. Based on ICD-9 Code Data from Kaiser Permanente Northern California Patient Database.
American Heart Association. Heart Disease and Stroke Statistics – 2005 Update. Available at:
http://www.americanheart.org/downloadable/heart/1105390918119HDSStats2005Update.pdf. Thom T, et al. Circulation. 2006;113:e85-e151. Rosamond W, et al. Circulation.
2007;115:e69-e171. Rosamond W, et al. Circulation. 2008;117:e25-e146. Lloyd-Jones D, et al. Circulation. 2009;119:e21-e181. Lloyd-Jones D, et al. Circulation. 2010;121:e46e215. Roger VL, et al. Circulation. 2011;123:e18-e209. Roger VL, et al. Circulation. 2011;123:e18-e209. Yeh RW, et al. N Engl J Med. 2010;362:2155-2165.
PCI is Inherently Thrombogenic
vWF, Tissue Factor
Thrombin Generation
• Indirect thrombin inhibitors:
– Unfractionated heparin
– LMWH
• Direct thrombin inhibitors:
– Bivalirudin
Collagen Exposed
Platelet Activation
• Aspirin
• P2Y12 inhibitors
• GP IIb/IIIa inhibitor
GP = glycoprotein. LMWH = low-molecular weight heparin. PCI = percutaneous coronary intervention. vWF = von Willebrand factor.
Antiplatelet Agents
ADP = adenosine diphosphate. PAR = protease-activated receptor. TxA2 = thromboxane A2.
Desai NR, Bhatt DL. JACC Cardiovasc Interv. 2010;3:571-583.
Clinically Relevant Dilemmas that We Face in
Managing Patients with ACS
• Optimal Dose of Oral Antiplatelet Therapies:
– What is the optimal dose of aspirin for patients with ACS?
– Is there an optimal dose of clopidogrel in ACS and should that
vary in patients after PCI?
– What is the optimal management strategy for medically
managed patients?
– What is optimal dose of prasugrel, especially in patients <60 kg
and older patients >75 years of age to decrease bleeding risk?
– Does the dose of aspirin play a role in patients treated with
ticagrelor?
Clinically Relevant Dilemmas that We Face in
Managing Patients with ACS (cont’d)
• Role of Platelet Function Testing in Choosing/altering
Antiplatelet Therapies:
– It has been well established that there is more variability in
response to clopidogrel than with the more potent agents
prasugrel and ticagrelor
– Recent evidence indicates that on-treatment platelet aggregation
predicts future risk of stent thrombosis or MACE
– Recent evidence also shows that increasing the loading or
maintenance dose of clopidogrel in hyporesponders improves
platelet response
– Is there evidence to support routine platelet function testing?
MACE = major adverse cardiovascular event.
Clinically Relevant Dilemmas that We Face in
Managing Patients with ACS (cont’d)
• Genetic Testing
– It has been well established that a family of cytochrome P450
enzymes metabolizes clopidogrel to its active form
– Recent evidence shows that patients who are treated with
clopidogrel and are carriers of loss-of-function CYP2C19
polymorphism have an increased CV risk that led to an FDA
warning
– Are there other polymorphisms besides CYP2C19 that need to
be tested?
– Is there evidence that warrants routine genetic testing?
CV = Cardiovascular. FDA = US Food and Drug Administration.
Clinically Relevant Dilemmas that We Face in
Managing Patients with ACS (cont’d)
• Potential Drug-drug Interaction:
– Ex vivo evidence using platelet function testing has shown that
PPIs decrease the efficacy of clopidogrel
– Registry analysis has shown that use of PPIs in patients on
clopidogrel increases their risk of future events
– Retrospective analyses of randomized trials has failed to show
that PPIs adversely affect the efficacy of clopidogrel
– A randomized prospective trial has shown that PPIs do not
adversely affect the efficacy of clopidogrel. The result has also
shown that PPI use provides better GI protection
– Should PPIs be used routinely in patients on clopidogrel or on
more potent antiplatelet agents?
GI = gastrointestinal. PPI = proton pump inhibitor.
Conclusions: Optimal Dose of Antiplatelet
Agents
• Evidence shows that low-dose aspirin seems to be as efficacious as
high-dose aspirin, with lower risk of GI bleeding and no difference in
major bleeding in PCI as well as non-PCI patients with ACS
• Evidence shows that high-dose clopidogrel is not beneficial in all
patients with ACS. However, it seems to be more efficacious in
lowering the risk of CV death/MI/stroke in patient with ACS
undergoing PCI, although the bleeding risk is also increased
• Prasugrel does not have a role in medical management of ACS,
though it does in patients with ACS undergoing PCI; when used, 5 mg
should be considered in the underweight and the elderly
• Patients with ACS managed invasively or medically on ticagrelor
should receive low-dose aspirin
Conclusions: Platelet Function Testing, Genetic
Testing, and PPI Interaction
• Current guidelines do not recommend routine platelet function
testing
• Current guidelines do not recommend routine genetic testing
• Current guidelines do not recommend routine use of PPIs;
however, use of PPIs in patients with high risk of GI bleeding
is advised
Thank You!
Pease turn in your survey and evaluation
as you depart.