Leadership. Knowledge. Community. USE OF ANTIPLATELET THERAPY IN PATIENTS WITH DIABETES Working Group: Maria E. Wolfs, MD, FRCP; Rémi Rabasa-Lhoret, MD,

Slides:



Advertisements
Similar presentations
Leadership. Knowledge. Community. Antiplatelet Therapy for the Primary Prevention of Vascular Events Working Group: Alan D. Bell, MD, CCFP and James D.
Advertisements

Update on Anti-platelets Gabriel A. Vidal, MD Vascular Neurology Ochsner Medical Center October 14 th, 2009.
THE ACTION TO CONTROL CARDIOVASCULAR RISK IN DIABETES STUDY (ACCORD)
PCI - A prospective, randomized, double- blind substudy of patients undergoing PCI in the CURE trial.
Keith A A Fox Royal Infirmary & University of Edinburgh CURE and PCI-CURE.
Leadership. Knowledge. Community. Canadian Cardiovascular Society Antiplatelet Guidelines COMBINATION WARFARIN + ASA THERAPY WHEN: TO USE, TO CONSIDER,
Anti thrombotics in STEMI Journal review Dr Nithin P G.
Canadian Diabetes Association Clinical Practice Guidelines Acute Coronary Syndromes and Diabetes Chapter 26 Jean-Claude Tardif, Phillipe L. L’Allier, David.
K Fox, W Remme, C Daly, M Bertrand, R Ferrari, M Simoons On behalf of the EUROPA investigators. The diabetic sub study of.
Canadian Cardiovascular Society Antiplatelet Guidelines
North of Tyne anti-platelet guidelines: use in primary care Jane S Skinner Consultant Community Cardiologist.
Leadership. Knowledge. Community. Canadian Cardiovascular Society Antiplatelet Guidelines HEART FAILURE Working Group: Alan D. Bell, MD, CCFP; James D.
CAPRIE: Clopidogrel versus Aspirin in Patients at risk of Ischemic Events Purpose To assess the relative efficacy of the antiplatelet drugs clopidogrel.
TNT: Study Design Treating to New Targets 2 5 years 10,001 Patients Clinically evident CHD LDL-C 130  250 mg/dL following up to 8-week washout and 8-week.
Giuseppe Biondi-Zoccai Division of Cardiology, University of Turin, Turin, Italy.
Luigi Oltrona Visconti Divisione di Cardiologia IRCCS Fondazione Policlinico S. Matteo Pavia Sindromi coronariche acute nei pazienti con fibrillazione.
Facts and Fiction about Type 2 Diabetes Michael L. Parchman, MD Department of Family & Community Medicine September 2004.
Canadian Diabetes Association Clinical Practice Guidelines Vascular Protection in People with Diabetes Chapter 22 James A. Stone, David Fitchett, Steven.
TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel TRITON-TIMI 38 TRITON-TIMI 38 Elliott M. Antman, MD.
VBWG IDEAL: The Incremental Decrease in End Points Through Aggressive Lipid Lowering Study.
Effect of Aspirin Dose on Platelet Reactivity in Diabetic Patients Effect of Aspirin Dose on Platelet Reactivity in Diabetic Patients Paul A. Gurbel, MD.
Leadership. Knowledge. Community. Antiplatelet Therapy for Secondary Prevention Beyond One Year Following ACS or PCI Working Group: Anil Gupta MD, FRCPC,
ACS is a major public health challenge In the US:  Over 1.5 million people experience ACS annually 1 In the EU:  ACS is the most common cause of death,
Clopidogrel in ACS: Overview Investigator, TIMI Study Group Associate Physician, Cardiovascular Division, BWH Assistant Professor of Medicine, Harvard.
Leadership. Knowledge. Community. Canadian Cardiovascular Society Antiplatelet Guidelines ANTIPLATELET THERAPY IN PATIENTS WITH CHRONIC KIDNEY DISEASE.
Leadership. Knowledge. Community. Canadian Cardiovascular Society Antiplatelet Guidelines Antiplatelet Therapy for Vascular Prevention in Patients with.
COURAGE: Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation Purpose To compare the efficacy of optimal medical therapy (OMT)
Combination Therapy in Acute Coronary Disease Elizabeth Gabrielle PA-S Lock Haven University February 2009.
Cardiovascular Disease in Women Module V: Prognosis and Treatment Outcomes.
VBWG CHARISMA Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance trial.
ACTIVE Clopidogrel plus Aspirin versus Aspirin in Patients Unsuitable for Warfarin.
C.R.E.D.O. C lopidogrel for the R eduction of E vents D uring O bservation Multicenter Multinational (USA, Canada) Prospective Randomized Double Blind.
PPAR  activation Clinical evidence. Evolution of clinical evidence supporting PPAR  activation and beyond Surrogate outcomes studies Large.
Prasugrel vs. Clopidogrel for Acute Coronary Syndromes Patients Managed without Revascularization — the TRILOGY ACS trial On behalf of the TRILOGY ACS.
Aspirin Resistance: Significance, Detection and Clinical Management of This Real Phenomenon Webcast May 10 th, 2004 Sponsored by.
Glycemic Control: When the Lower is Not the “Better”?
Aim To determine the effects of a Coversyl- based blood pressure lowering regimen on the risk of recurrent stroke among patients with a history of stroke.
ACCP Cardiology PRN Journal Club. Announcements Thank you attending the ACCP Cardiology PRN Journal Club – Thank you if you attended last time or have.
What’s New in Acute Coronary Syndromes? Claudia Bucci BScPhm, PharmD Clinical Coordinator, Cardiovascular Diseases Sunnybrook Health Sciences Centre 13.
The Relative Safety and Efficacy of Clopidogrel in Women and Men: A Sex-Specific Meta-Analysis Jeffrey S. Berger, Deepak L. Bhatt, Christopher P. Cannon,
Vorapaxar for Secondary Prevention in Patients with Prior Myocardial Infarction Benjamin M. Scirica, MD, MPH On behalf of the TRA 2°P-TIMI 50 Steering.
* Based on post hoc analysis of individual outcome events (N=19,185). 1 Data on file, Sanofi Pharmaceuticals, Inc. 2 Gent M. Circulation. 1997; 96 (suppl):
HOPE: Heart Outcomes Prevention Evaluation study Purpose To evaluate whether the long-acting ACE inhibitor ramipril and/or vitamin E reduce the incidence.
Naotsugu Oyama, MD, PhD, MBA A Trial of PLATelet inhibition and Patient Outcomes.
MANAGING ATHERO- THROMBOTIC RISK Early impact and long-term benefit of antiplatelet therapy What is the optimal duration of antiplatelet therapy? Giuseppe.
Cardiovascular Risk Diabetes And Aspirin A Closer look into the evidence-base Howard Van IM2 Ahraaz Wyne IM1 The University of Western Ontario London Health.
Pocket Guide to Anticoagulation in AF & Dual Antiplatelet Therapy in ACS Rumi Jaumdally 2015 This brief presentation will summarise the recently published.
A Review of – Clopidogrel and Aspirin versus Aspirin Alone for the Prevention of Atherothrombotic Ted Williams Pharm D Candidate Monday Lab.
C-1 Efficacy of the Combination: Meta-Analyses Donald A. Berry, Ph.D. Frank T. McGraw Memorial Chair of Cancer Research University of Texas M.D. Anderson.
Medical Management of Claudication: Just Walk it Off!!
Hypothesis: baseline risk status of the patients and proximity to a recent cardiovascular event influence the response to dual anti-platelet therapy. Patients.
ESPS-2: European Stroke Prevention Study s Multicentre, randomized, double-blind, placebo-controlled trial s 6,602 patients randomized within 3 months.
TRITON TIMI-38 STEMI cohort Primary End Point (CV death, MI and stroke at 15 months) Adapted from Montalescot et al. ESC Time (days)
Reduction in Ischemic Events with Ticagrelor in Diabetic Patients from the PEGASUS-TIMI 54 Trial Deepak L. Bhatt, MD, MPH, Marc P. Bonaca, MD, MPH, Sameer.
The Use of Aspirin for Primary Prevention of Cardiovascular Diseases
Date of download: 6/21/2016 From: Aspirin for the Primary Prevention of Cardiovascular Events: A Systematic Evidence Review for the U.S. Preventive Services.
수요저널 우종신. ACC/AHA Guideline Focused Update 2011 Class I 1. After PCI, use of aspirin should be continued indefinitely. (Level of Evidence.
_________________ Caitlin M. Gibson, PharmD, BCPS
Reducing Adverse Outcomes after ACS in Patients with Diabetes Goals
The Big Antiplatelet Debate Why I Prefer Prasugrel Over Ticagrelor
Learning Objectives. Learning Objectives Variable Response to Clopidogrel.
Comprehensive Diabetes Care
RAAS Blockade: Focus on ACEI
The Hypertension in the Very Elderly Trial (HYVET)
Would you recommend extending DAPT >1 year post-MI?
What oral antiplatelet therapy would you choose?
Factor Xa Inhibitors in Coronary Artery Disease
Comparison of outcomes in patients with versus patients without diabetes; primary outcome event rate (CV death, non-fatal MI and non-fatal CVA) as a percentage.
Section C: Clinical trial update: Oral antiplatelet therapy
Prasugrel and ticagrelor versus clopidogrel; risk ratio with 95% CIs for the primary composite end point of cardiovascular death, non-fatal myocardial.
Presentation transcript:

Leadership. Knowledge. Community. USE OF ANTIPLATELET THERAPY IN PATIENTS WITH DIABETES Working Group: Maria E. Wolfs, MD, FRCP; Rémi Rabasa-Lhoret, MD, PhD Canadian Cardiovascular Society Antiplatelet Guidelines

Objectives Interpret the Canadian Cardiovascular Society Guideline recommendations regarding the use of antiplatelet therapy in patients with diabetes. Appropriately use antiplatelet agents for primary and secondary vascular prevention. Recognize the difference in the effect of antiplatelet agents in patients with and without diabetes. Evaluate the evidence regarding the use of antiplatelet agents in patients with diabetes. © TIGC

Case A 65 year old man suffering from type 2 diabetes for 15 years Currently taking ramipril 10 mg OD, rosuvastatin 20 mg OD and metformin 500 mg TID He has no history of CAD, CVD or PAD. The physical examination is unremarkable. He is concerned about not taking any ASA. © TIGC

Antiplatelet management What antiplatelet therapy, if any, would you suggest ? A. No antiplatelet therapy B. ASA 80 mg C. Clopidogrel 75 mg D. ASA 80 mg + Clopidogrel 75 mg © TIGC

Mechanisms contributing to platelet dysfunction In patients with diabetes mellitus PKC ROS/NOS IRS-1 Ca ++ TF PGI 2 NO Endothelial cells H2OH2O P2Y 12 ADP HYPERGLYCAEMIA Increased P-selectin expression Osmotic effect Activation of PKC Decreased membrane fluidity by glycation of surface proteins DEFICIENT INSULIN ACTION Impaired response to NO and PGI 2 IRS-dependent factors: Increased intracellular Ca ++ degranulation ASSOCIATED METABOLIC CONDITIONS Obesity Dyslipidemia Inflammation OTHER CELLULAR ABNORMALITIES PLATELETENDOTHELIAL DYSFUNCTION Increased platelet turnover Upregulation of P2Y 12 signalling Increased intracellular Ca ++ Oxydative stress Increased P-selectin and GP expression Increased production of TF Decreased NO and PGI 2 production Ferreiro JL, Angiolllo DJ. Circulation 2011; 123:

Diabetes in “primary prevention” Antiplatelet agents Hayden M et al. U.S. Preventive Services Task Force. Ann Intern Med. 2002;136: The proportion of diabetic patients in primary prevention studies is SMALL. PPP: 17% HOT: 8% PHS: 2% BMD: 2% TPT: 2% Hayden M et al. U.S. Preventive Services Task Force. Ann Intern Med. 2002;136: < 20 %

Diabetes in“primary prevention”: Antiplatelet agents “Antithrombotic Trialists Collaboration” 2002 BMJ 2002, vol 24: Much of the new information comes from the early treatment diabetic retinopathy study, in which 3711 people with diabetes (and, generally, no history of myocardial infarction or stroke) were allocated to receive 650 mg aspirin dailyor placebo. % odds reduction 7%

Early treatment diabetic retinopathy Study report 14 © TIGC ETDRS Investigators. JAMA 1992; 268: CAD baseline : 8%

ASA and diabetes: 2008 JPAD © TIGC Ogawa H et al. JAMA 2008 (300) 18;

ASA and diabetes: 2008 JPAD: Baseline clinical characteristics © TIGC Ogawa H et al. JAMA 2008 (300) 18;

ASA and diabetes: 2008 JPAD: Primary end point © TIGC Ogawa H et al. JAMA 2008 (300) 18;

ASA and diabetes: 2008 JPAD: Secondary end point © TIGC Ogawa H et al. JAMA 2008 (300) 18;

ASA and diabetes: 2008 JPAD: Primary end point if 65 years or older © TIGC Ogawa H et al. JAMA 2008 (300) 18;

ASA and diabetes: 2008 JPAD: Subgroup analysis © TIGC Ogawa H et al. JAMA 2008 (300) 18;

ASA and diabetes: 2008 POPADAD (with PAD) © TIGC Belch J et al. BMJ 2008

ASA and diabetes: 2008 POPADAD (with PAD) © TIGC Belch J et al. BMJ 2008

Asymptomatic “PAD” and diabetes ASA ineffective (but ABI 0.9…) © TIGC POPADAD Belch J et al. BMJ 2008

Meta-analysis in primary prevention 2009 ASA and diabetes © TIGC De Berardis G et al. BMJ 2009; 399

Meta-analysis in primary prevention 2009 ASA and diabetes: Studies, dose and Tx duration De Berardis G et al. BMJ 2009; 399

Meta-analysis in primary prevention 2009 ASA and diabetes: Major CV events © TIGC De Berardis G et al. BMJ 2009; 399

Meta-analysis in primary prevention 2009 ASA and diabetes: MI © TIGC De Berardis G et al. BMJ 2009; 399

Meta-analysis in primary prevention 2009 ASA and diabetes: Stroke © TIGC De Berardis G et al. BMJ 2009; 399

Meta-analysis in primary prevention 2009 ASA and diabetes: CV death © TIGC De Berardis G et al. BMJ 2009; 399

Meta-analysis in primary prevention 2009 ASA and diabetes: Total mortality © TIGC De Berardis G et al. BMJ 2009; 399

ASA and primary prevention Comparison diabetics and non-diabetics © TIGC Calvin AD et al. Diabetes Care 2009; 32:

26 ®® Antiplatelet therapy in patients with diabetes Primary prevention 1.There is currently no evidence to recommend routine use of ASA at any dose for the primary prevention of vascular ischemic events in patients with diabetes (Class III, Level A). 2.For patients with diabetes aged more than 40 years and at low risk for major bleeding, low-dose ASA ( mg daily) may be considered for primary prevention in patients with other cardiovascular risk factors for which its benefits are established (Class IIb, Level B).

27 ®® Antiplatelet therapy in patients with diabetes Primary prevention

Case A 65 year old man suffering from type 2 diabetes for 15 years is currently taking ramipril 10 mg OD, rosuvastatin 20 mg OD and metformin 500 mg TID. He has no history of CAD, CVD or PAD. The physical examination is unremarkable. He is concerned about not taking any ASA. © TIGC

Antiplatelet management What antiplatelet therapy, if any, would you suggest ? A. No antiplatelet therapy B. ASA 80 mg C. Clopidogrel 75 mg D. ASA 80 mg + Clopidogrel 75 mg © TIGC

Diabetes and Secondary Prevention: CAPRIE 1996 Clopidogrel and ASA to reduce MI, IS and VD/ yr High-risk Population ASAClopidogrel Event rate % RRR (%) ARR (%) NNT Total CAPRIE population Patients with PAD Patients with multivascular territory involvement Patients with a history of more than one ischemic event NA Patients with diabetes NANANANA Patients with previous CABG Patients taking lipid-lowering agents NA

Diabetes and secondary prevention: CAPRIE 1996 Reduction MI, IS, VD and Hosp for isch or bleeding events/yr High-risk Population ASAClopidogrel Event rate %RRR (%)ARR (%)NNT Total CAPRIE population Patients with PAD NA Patients with multivascular territory involvement NA Patients with a history of more than one ischemic event 36.5 / 3yr Patients with diabetes Patients with previous CABG Patients taking lipid-lowering agents

Clopidogrel vs ASA in secondary prevention CAPRIE: Diabetic patient subgroup Events : MI, IS, VD, hospitalization for ischemic event / bleeding Events prevented / 1000 pts/yr over aspirin non-diabetic All diabetics With insulin Annual event rate (%) Annual event rate (%) ASAClopidogrel 12,7 % 11,8 % 17,7 % 15,6 % 21,5 % 17,7 % p = Bhatt et al. AJC 2002 Sep 15;90(6):625-8

Characteristic Hazard Ratio and 95% CI DiabetesYes No HypertensionYes No HypercholesterolemiaYes No History of CABGYes No History of PCIYes No History of MI Yes No History of Stroke Yes No RF Only (Asymptomatic) Documented AT (Symptomatic) CHARISMA 2006: Clopidogrel + ASA vs ASA only Primary endpoint (MI, IS and VD) by subgroups Clopidogrel Better Placebo Better Adapted from Bhatt DL, Fox KA, Hacke W, et al. 2006, in press. RF= Risk Factors AT= Atherothrombosis RF= Risk Factors AT= Atherothrombosis

34 ®® Antiplatelet therapy in patients with diabetes Secondary prevention 3.Low-dose ASA therapy ( mg daily) may be considered for secondary prevention in patients with diabetes and manifest vascular disease for which its benefits are established (Class I, Level A). 4.Clopidogrel 75 mg daily may be considered for secondary prevention in patients with diabetes who are unable to tolerate ASA (Class IIa, Level B).

35 ®® Antiplatelet therapy in patients with diabetes Secondary prevention

“What if” ACS The same 65 year old man comes back to your office after a hospitalization for ACS with two coated stents implanted. He is mixed up about his antiplatelet regimen and understands that ASA is important. How would that change your choice of antiplatelet therapy? © TIGC

A Roussin Kaplan–Meier curves for prasugrel versus clopidogrel Patients with DM vs no DM from the TRITON-TIMI 38 trial DM No DM Primary End Point TIMI Major Bleeding

Kaplan–Meier curves for prasugrel versus clopidogrel Patients with diabetes mellitus from the TRITON-TIMI 38 trial Wiviott SD et al. Circulation 2008;118(16):1626–36 Primary Efficacy End Point Primary Efficacy End Point n=3,146 End Point (%) Timi Major Non-CABG Bleeds Timi Major Non-CABG Bleeds Clopidogrel Prasugrel HR 0.70; p< Days Clopidogrel Prasugrel

PLATO (ticagrelor vs. clopidogrel) Diabetes substudy primary end point James S et al. European Heart Journal 2010 © TIGC

PLATO (ticagrelor vs. clopidogrel) Diabetes substudyTotal mortality James S et al. European Heart Journal 2010 © TIGC

PLATO (ticagrelor vs. clopidogrel) Diabetes substudyMajor bleeding James S et al. European Heart Journal 2010 © TIGC

PLATO (ticagrelor vs. clopidogrel) Diabetes substudy Primary end point according to baseline HbA1c James S et al. European Heart Journal 2010 © TIGC

PLATO (ticagrelor vs. clopidogrel) Diabetes substudy Major bleeding according to baseline HbA1c © TIGC James S et al. European Heart Journal 2010

Efficacy of Antiplatelet Therapies in ACS Results in the Diabetes Mellitus Subgroups (Adapted from Ferreiro JL et al. Circulation 2011; 123: ) Study# ptsRegimen Primary end- point Results overall # pts DM Results in DM Cure ASA+CL VS ASA CV death, non fatal MI, stroke at 1 yr 9.3 vs 11.4% RR= vs 16.7% RR=0.84 ns PCI- CURE ASA+CL VS ASA Cv death, MI or urgent TVR at 30 days 4.5 vs 6.4% RR= vs 16.5% RR=0.77 ns CREDO2 116 ASA+CL VS ASA Death, MI or stroke at 1 yr 8.5 vs 11.5% RRR=26.9% 560 % NA RRR=11.2% ns COMMIT ASA+CL VS ASA Death, reinfarct or stroke at discharge or 28 days 9.2 vs 10.1% OR=0.91 NA CLARITY3 491 ASA+CL VS ASA Occluded infarct-related artery on angiography or death or recurrent MI before angiography 15 vs 21.7% OR= NA PCI- CLARITY ASA+CL VS ASA CV death, recurrent MI or stroke at 30 days 3.6 vs 6.2% OR= vs 10.1% OR=0.61 ns TRITON- TIMI ASA+PRA VS ASA+CL CV death, non-fatal MI or non-fatal stroke at 15 mo. 9.9 vs 12.1% HR= vs 17% HR=0.70 PLATO ASA+TICA VS ASA+CL Death from vascular causes, MI or stroke at 12 mo. 9.8 vs 11.7% HR= vs 16.2% HR=0.88 ns

Ongoing Studies ASCEND and ACCEPT - D ASCEND UK ASA 100 mg and Omega-3 Randomized double blind for 5 years 10,000+ patients > 40 yrs ACCEPT – D Italy ASA 100 mg + simvastatine mg Randomized open for 5 years 5170 patients > 50 yrs © TIGC