DECLARATION OF CONFLICT OF INTEREST

Transcription

1 DECLARATION OF CONFLICT OF INTEREST

2 How to manage antiplatelet treatment in patients with diabetes in acute coronary syndrome Lars Wallentin Professor of Cardiology, Chief Researcher Cardiovascular Science Uppsala Clinical Research Centre, Uppsala University, Uppsala, Sweden

3 Disclosures for Lars Wallentin AstraZeneca Boehringer Ingelheim Bristol-Myers Squibb GlaxoSmithKline Schering-Plough Eli Lilly & Co. Research grant Research grant Research grant Research grant Research grant Research grant Regado Biosciences Athera Biotechnologies Evolva Consultancy Consultancy Consultancy

4 Acute Coronary Syndrome ECG. Troponin. Aspirin + P2Y12 inhib Beta-blocker + Nitrate ACC/AHA/ESC ACS treatment guidelines Persistent ST-segment elevation Primary PCI + GpIIb/IIIa inh Or Thrombolysis High risk + GpIIb/IIIa inh. Cor angio urgent PCI/CABG No persistent ST-elevation + Fonda/LMWH UFH/Bivalirudin Intermediate risk Cor angio 1 7 days Aspirin + P2Y12 inhib + Betablocker + Statin + ACE-inhib Low risk Stress test Pos Neg Aspirin (+ Statin)

5 Prospective study of glucose metabolism in patients with Acute Myocardial Infarction in Sweden Age < 80 years At hospital discharge At 3 months after discharge 28% 20% 20% 32% Norhammar et al, Lancet 2002; 359: 2140

6 Diabetes mellitus in IHD 399,006 patients in RIKS-HIA

7 Prevalence of Diabetes Mellitus in Patients with STEMI According to International Registers Hospitals: RIKS-HIA 67 (85%); BLITZ 296 (87%); NRMI 1432 (19%); EuroHeart 103 in 25 Eur countries; ENACT 390 in 29 Eur countr.

8 Mortality, % Cumulative Incidence of All-Cause Mortality Through 1 Year After ACS Diabetes Subgroup Analysis 11 TIMI Trials, >62,000 pts 10,613 diabetics (17.1%) 14 STEMI Diabetes No Diabetes UA/STEMI Diabetes No Diabetes P< STEMI P< P< P< UA/NSTEMI 0 No. at Risk STEMI Diabetes No diabetes UA/NSTEMI Diabetes No diabetes Donahoe SM et al. JAMA. 2007;298: Days after ACS

9 Probability of death One year mortality Kaplan-Meier 1- survival analysis in all patients Adjusted RR = 1.48 ( ); p<0.001 Diabetes n = No diabetes n = days

10 1-year mortality (%) in three different age groups of AMI patients. % No Diabetes OR = OR = < >=75 Age (years) Diabetes OR = 1.7 Norhammar et al. European Heart Journal 2003; 24:

11 Randomised trials N patients Composite endpoint of MI, stroke, and cardiovascular death RR (95% CI) Fibrinolytic ACE-inhibitor Aspirin Clopidogrel FTTC HOPE ATC CURE Beta-blocker Statin GPIIb/IIIa MIAMI HPS Epic, Epilog, Epistent Diabetes Yes No Therapy better Therapy worse

12 Multiple adjusted treatment effects on one year mortality Reperfusion Heparin/Lmwh Aspirin Betablockade Lipidlowering ACE-inhibition Revasc <14 d OR Diabetes Yes No

13 Probability of death or MI FRISC II: Diabetes mellitus.30 DM Noninvasive (n=144) DM Invasive (n=155) Noninvasive (n=1091).05 Invasive (n=1067) Lancet 2000; 356: 9-16

14 Odds/hazard ratio Diabetes as Predictor of Stent Thrombosis at 1 Year in the Era of DES 5 4 OR=2.0 ( ) OR=2.8 ( ) HR=3.7 ( ) HR=2.03 ( ) IDDM IDDM Diabetes Diabetes Kuchulakanti et al. Circulation 2006 Urban et al. Circulation 2006 Iakovou et al. JAMA 2005 Daemen et al. Lancet 2007

15 % 2,0 Stenttrombos i SCAAR 1,5 Diabetes n=7722 1,0 No diabetes n= ,5 0,0 0 1 År 2

16 CURE: Outcomes With Clopidogrel in Various Subgroups Characteristic Percentage of Patients with Event No. of Patients Clopidogrel + ASA Placebo + ASA Overall Associated MI No associated MI Male sex Female sex yr old > 65 yr old ST-segment deviation No ST-segment deviation Enzymes elevated at entry Enzymes not elevated at entry Diabetes No diabetes Low risk Intermediate risk High risk History of revascularization No history of revascularization Revascularization after randomization No revascularization after randomization Yusf S et al. N Engl J Med. 2001;345: Relative Risk (95% CI) Clopidogrel Better Placebo Better

17 Efficacy of New Drugs/Approaches in Reducing Adverse Outcomes in Diabetes Mellitus From Large-Scale Clinical Trials Study % of Events Hazard Ratio (95% confidence interval) Standard New Drug/Approach TRITON-TIMI ( ) PLATO ( ) CURRENT OASIS ( ) (PCI Cohort) New Drug/Approach Better Standard Clopidogrel Better CURRENT-OASIS= Clopidogrel Optimal Loading Dose Usage to Reduce Recurrent Events Optimal Antiplatelet Strategy for Interventions; PCI=percutaneous intervention; PLATO= A Study of Platelet Inhibition and Patient Outcomes; TRITON- TIMI= Trial To Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel Thrombolysis in Myocardial Infarction. Reprinted with permission from Ferreiro JL, Angiolillo DJ. Circulation In press

18 TRITON TIMI-38: CV Death/MI/Stroke by Diabetic Status Pras Clop Reduction in Risk No DM 9.2% 10.6% 14% DM No Insulin 11.5% 15.3% 26% DM on Insulin 14.3% 22.2% 37% Prasugrel better Clopidogrel better Wiviott SD, Braunwald E, Angiolillo DJ et al. Circulation. 2008;118:

19 Endpoint (%) TRITON: Diabetic Subgroup CV Death / MI / Stroke TIMI Major NonCABG Bleeds HR 0.70 P<0.001 NNT = Days N=3146 Clopidogrel Prasugrel Prasugrel Clopidogrel

20 CV death, MI, or stroke (%) PLATO diabetes: Primary composite endpoint Diabetes Ticagrelor (n=2326) Clopidogrel (n=2336) HR (95% CI) = 0.88( ) 16.2% 14.1% 10 p for interaction = % 8.4% 5 0 Days after randomisation No diabetes Ticagrelor (n=6999) Clopidogrel (n=6952) HR (95% CI) = 0.83( ) Primary endpoint benefit with ticagrelor was consistent with the overall PLATO trial results No interaction between diabetes status and treatment was observed (p=0.49) CI, confidence interval; CV, cardiovascular; HR, hazard ratio; MI, myocardial infarction. James S, et al. Eur Heart J 2010;31:

21 All-cause mortality (%) PLATO diabetes: All-cause mortality Diabetes Ticagrelor (n=2326) Clopidogrel (n=2336) HR (95% CI) = 0.82( ) p for interaction = % 7.0% 5.0% 3.7% 2 0 Days after randomisation CI, confidence interval; HR, hazard ratio. James S, et al. Eur Heart J 2010;31: No diabetes Ticagrelor (n=6999) Clopidogrel (n=6952) HR (95% CI) = 0.77( ) All-cause mortality benefit with ticagrelor was consistent with the overall PLATO trial results No interaction between diabetes status and treatment was observed (p=0.66)

22 Major bleeding (%) 15 PLATO diabetes: Major bleeding 14.8% 14.1% 10 p for interaction = % 10.0% 5 Diabetes Ticagrelor (n=2305) Clopidogrel (n=2316) HR (95% CI) = 0.95( ) No diabetes Ticagrelor (n=6928) Clopidogrel (n=6870) HR (95% CI) = 1.08( ) Days after randomisation Bleeding occurred with similar frequency in the ticagrelor and clopidogrel groups, independent of diabetes status No interaction between diabetes status and treatment was observed (p=0.21) CI, confidence interval; HR, hazard ratio. James S, et al. Eur Heart J 2010;31:

23 Conclusions Diabetes mellitus patients with ACS have times higher mortality women <60 years 5 times higher have same or better effect of platelet inhibitors and other ACS treatments might be undertreated with platelet inhibition and other ACS treatments

24 Treatment of arterial thrombosis Risk for ischemic events Risk for bleeding