Mega JL, et al. N Engl J Med 2009;360:354-62. Genetic Effects on Pharmacokinetic and Pharmacodynamic Responses to Clopidogrel Mega JL, et al. N Engl J.

Slides:

Advertisements

Similar presentations

Description of Each Study in the Cross Trial Safety Analysis Solomon SD, et al. Circulation 2008 [Epub Mar 31]

Advertisements

Montalescot G, et al. Lancet 2009;373: Trial profile Montalescot G, et al. Lancet 2009;373:

Prospective Evaluation of On-Clopidogrel Platelet Reactivity Over Time in Patients treated with Percutaneous Coronary Intervention. Relationship with Gene.

Montalescot G et al. Lancet 2008;372:1-9. Mid- and long-term outcomes of STEMI patients treated with prasugrel, compared with clopidogrel and undergoing.

Trial profile Fox K et al. Lancet 2008;372:

Giuseppe Biondi-Zoccai Division of Cardiology, University of Turin, Turin, Italy.

COURAGE: Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation Purpose To compare the efficacy of optimal medical therapy (OMT)

Randomized, double-blind, multicenter, controlled trial.

PRO-GR: A Prospective, Randomized, Crossover Study of Maintenance High-Dose Clopidogrel vs. Prasugrel in Clopidogrel Resistant Patients With and Without.

The Influence of Proton Pump Inhibitors on Clinical Outcomes After Successful Percutaneous Coronary Intervention Kishore J. Harjai, MD, FACC Chetan Shenoy,

Effect of Switching Antithrombin Agents for Primary Angioplasty in Acute Myocardial Infarction The HORIZONS-SWITCH Analysis HORIZONS AMI Dangas G, et al.

Naotsugu Oyama, MD, PhD, MBA A Trial of PLATelet inhibition and Patient Outcomes.

The ACTIVE Investigators. N Engl J Med 2009 Apr 3 [Epub]

CARDIOLOGIA INV 1 CAREGGI - FIRENZE Objective To determine whether nonresponsiveness to clopidogrel as revealed by high in vitro residual platelet reactivity.

Mechanism of Action of Aspirin Carlo Patrono, et al, N Engl J Med 2005;353:

The ILLUMINATE Study: Enrollment and Outcomes Philip Barter, et al. N Engl J Med 2007;357:

¨ 8 European countries, 48 centres Stent implantation Double-blind randomisation n = 1005 Clopidogrel 300mg od Aspirin 325mg od Clopidogrel 75mg od Aspirin.

NSTE Acute Coronary Syndromes

Trial profile Prakash Deedwania, et al. Lancet 2006; 368:

- Published online December 23, 2008 DOI: /S (08) Study sponsored and funded by Assistance Publique.

Baseline Characteristics of the Patients* - Part I The ONTARGET Investigators. N Engl J Med 2008 [Epub on Mar 31]

TRITON TIMI-38 STEMI cohort Primary End Point (CV death, MI and stroke at 15 months) Adapted from Montalescot et al. ESC Time (days)

Enrollment and Outcomes Duckworth W, et al. N Engl J Med 2009;360:

TRITON TIMI-38 STEMI cohort Clopidogrel Under Fire: Is Prasugrel in Primary PCI or Recent MI Superior? Insights From TRITON-TIMI-38 Gilles Montalescot,

Date of download: 7/8/2016 Copyright © 2016 American Medical Association. All rights reserved. From: Reduced-Function CYP2C19 Genotype and Risk of Adverse.

Date of download: 7/8/2016 Copyright © The American College of Cardiology. All rights reserved. From: The Year in Non–ST-Segment Elevation Acute Coronary.

(p for noninferiority = 0.01)

New Anti-platelet Agents

The SPRINT Research Group

Flow of Individuals Through the Vitamin E and Vitamin C Components of the Physicians’ Health Study II Howard D. Sesso et al. JAMA 2008;300:

Bedside monitoring to adjust antiplatelet therapy for Coronary stenting N Engl J Med Nov 29;367: Prof. Soo-Joong Kim / R3 Yu Ho Lee.

Trial profile SAS denotes the Simvastatin in Aortic Stenosis Study

Figure 1 Ischaemic endpoints

Anne Masich, PharmD PGY1 Resident University of Maryland

LEADER trial: Primary Outcome

CYP2C19 Genotyping to Individualize Anti-platelet Therapy: Which one should we perform? How to interpret data? Is it ready for clinical practice? Alan.

The GRAVITAS trial Matthew J. Price MD, FACC, FSCAI

TNT: Baseline and final LDL cholesterol levels

Learning Objectives. Learning Objectives Variable Response to Clopidogrel.

11/12/2018 CYP2C19-Clopidogrel Development of these slides was supported by funding from the IGNITE Network. When using or adapting any of these slides.

11/12/2018 CYP2C19-Clopidogrel Development of these slides was supported by funding from the IGNITE Network. When using or adapting any of these slides.

A PRAGMATIC RANDOMIZED TRIAL OF CYP2C19 GENOTYPING IMPLEMENTATION FOLLOWING PERCUTANEOUS CORONARY INTERVENTION (PCI) Sony Tuteja, PharmD, MS

Table. Clinical Efficacy and Safety

ATLANTIC Trial design: Participants with STEMI being transported for primary PCI were randomized in the ambulance to ticagrelor 180 mg (n = 909) vs. placebo.

Robert W. Yeh et al. JACC 2017;70:

TNT Study: Baseline Characteristics of the Patients

Impact of clopidogrel loading dose on the safety and effectiveness of bivalirudin in patients undergoing primary angioplasty for acute myocardial infarction:

Impact of Platelet Reactivity Following Clopidogrel Administration

P2Y12 blockade versus placebo; risk ratio with 95% CIs for the primary composite end point of cardiovascular death, non-fatal myocardial infarction and.

Simon T, et al. N Engl J Med 2009;360:363-75

Enrollment and Outcomes

Inclusion Criteria for Patients with Multiple Atherothrombotic Risk Factors and for Those with Established Cardiovascular Disease Deepak L.Bhatt, et al,

Overall (n=301) Acute/Subacute (n=149) Late (n=152) p Presentation

Flow diagram for exclusions of trials identified RCT indicates randomized controlled trial Hulten E, et al. Arch Intern Med 2006;166:

Baseline Characteristics of the Study Participants

Baseline Characteristics, Blood Pressures, and Laboratory Values

Baseline Characteristics of the Subjects*

Women’s Health Study: Baseline Characteristics Part 1

Collet JP, et al. Lancet 2009;373:309-17

Age-Standardized Rates of Death from Any Cause According to the Estimated GFR among 1,120,295 Ambulatory Adults Alan S.Go et al. N Engl J Med 2004; 351:

Entry, Randomization, and Follow-up of Patients in the Hypertension in the Very Elderly Trial Of the 461 patients who did not meet the protocol criteria,

Baseline Characteristics of Elderly Participants in the Cardiovascular Health Study,According to Quintiles of Cystatin C Michael G.Shlipak et al N Engl.

Baseline Characteristics of the Patients – Part I

Baseline Characteristics of the Patients - Part I

The ACCORD Study Group. NEJM 2010; Epub March 14

Comparison of Baseline Characteristics by Primary End Point

EMPA-REG OUTCOME: Cumulative incidence of the primary outcome

Ticagrelor versus prasugrel; risk ratio with 95% CIs for the primary composite end point, primary composite end point in those undergoing PCI, myocardial.

Prasugrel versus clopidogrel; risk ratio with 95% CIs for the primary composite end point of cardiovascular death, non-fatal myocardial infarction and.

Prasugrel and ticagrelor versus clopidogrel; risk ratio with 95% CIs for the primary composite end point of cardiovascular death, non-fatal myocardial.

Presentation transcript:

Mega JL, et al. N Engl J Med 2009;360:354-62

Genetic Effects on Pharmacokinetic and Pharmacodynamic Responses to Clopidogrel Mega JL, et al. N Engl J Med 2009;360:354-62

Relationship between CYP2C19 Genetic Classification and Pharmacokinetic and Pharmacodynamic Responses after the Administration of Loading and Maintenance Doses of Clopidogrel in Healthy Subjects Mega JL, et al. N Engl J Med 2009;360:354-62

Association between Status as a Carrier of a CYP2C19 Reduced-Function Allele and the Primary Efficacy Outcome or Stent Thrombosis in Subjects Receiving Clopidogrel Mega JL, et al. N Engl J Med 2009;360: Among 1459 subjects who were treated with clopidogrel and could be classified as CYP2C19 carriers or noncarriers, the rate of the primary efficacy outcome (a composite of death from cardiovascular causes, myocardial infarction, or stroke) was 12.1% among carriers, as compared with 8.0% among noncarriers (hazard ratio for carriers, 1.53; 95% CI, 1.07 to 2.19) (Panel A). Among 1389 subjects treated with clopidogrel who underwent PCI with stenting, the rate of definite or probable stent thrombosis (a key prespecified secondary outcome, defined as per the Academic Research Consortium) was 2.6% among carriers and 0.8% among noncarriers (hazard ratio, 3.09; 95% CI, 1.19 to 8.00) (Panel B).

Efficacy and Safety Outcomes at 15 Months in Subjects Treated with Clopidogrel, According to Genotype Status* Mega JL, et al. N Engl J Med 2009;360:354-62

Healthy Subject Pharmacokinetic and Pharmacodynamic Studies Mega JL, et al. N Engl J Med 2009;360: Supplementary Appendix

Baseline Characteristics of Clopidogrel Allocated Subjects in the TRITON-TIMI 38 Genetic Study and the Overall Trial Mega JL, et al. N Engl J Med 2009;360: Supp App

Cytochrome P450 Genes and Measured Alleles Mega JL, et al. N Engl J Med 2009;360: Supplementary Appendix

Genotyping Results in Clopidogrel Allocated Subjects by Gene and Predicted Metabolic Phenotype Mega JL, et al. N Engl J Med 2009;360: Supplementary Appendix

Baseline Characteristics of CYP2C19 Carriers and Non-carriers in Clopidogrel Treatment Arm in TRITON-TIMI 38 Mega JL, et al. N Engl J Med 2009;360: Supp App

CYP2C19 Genetic Effects on Pharmacokinetics (AUC 0-t ) and Pharmacodynamics (∆MPA) Following Clopidogrel Loading Dose and Maintenance Dose, by Dose Mega JL, et al. N Engl J Med 2009;360: Supplementary Appendix

Schematic Representation of the Metabolic Activation Pathway for Clopidogrel Mega JL, et al. N Engl J Med 2009;360: Supplementary Appendix