1. Canadian Diabetes Association Clinical Practice Guidelines Acute Coronary Syndromes and Diabetes Chapter 26 Jean-Claude Tardif, Phillipe L. L’Allier, David H. Fitchett

2. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Acute Coronary Syndrome Checklist SCREEN for DM among patients with ACS USE anti-platelet therapies, prasugrel or ticagrelor, instead of clopidogrel in patients with DM undergoing percutaneous coronary intervention (PCI) AVOID both hyper- and hypoglycemia among patients with DM admitted with ACS 2013

3. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Screen for DM Among Patients with ACS Diabetes is a strong risk factor for cardiovascular disease A significant proportion of patients with ACS have undiagnosed DM Screening for DM is essential among patients with ACS – Can use FPG, A1C or 75g OGTT – Consider standardized order sets

4. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Radke P W,et al. Eur Heart J 2010;31:2971-3. ACS Mortality in Diabetes vs. No Diabetes: Changes Across the Eras

5. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association All patients with DM and ACS should receive the same treatments as those without DM … with some differences

6. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Dual Anti-platelet Therapy in Patients with DM Diabetes  ↑ risk of recurrent atherothrombotic events, including stent thrombosis Low dose ASA (75-150 mg) is effective for secondary prevention Dual anti-platelet therapy (ASA + clopidogrel) has been standard of care for non-ST elevation acute coronary syndrome (NSTE ACS) but recurrent events continue to occur, especially in diabetes

7. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association TRITON Study: Prasugrel vs. Clopidogrel Days % of Patients 0 5 10 15 0306090180270360450 HR: 0.81 (0.73-0.90) p <.001 Prasugrel (n=6813) 12.1% 9.9% NNT = 46 Modified from Wiviott SD, et al. N Engl J Med. 2007;357(20):2001-2015. CV Death/MI/Stroke at 15 months n =13,608: ACS (STEMI or NSTE ACS) and Planned PCI CLOPIDOGREL 300 mg LD/ 75 mg MD PRASUGREL 60 mg LD/ 10 mg MD CV Death / MI / Stroke ACS = Acute Coronary Syndrome; STEMI = ST-elevation Myocardial Infarction; NSTE ACS = Non-ST-elevation Acute coronary Syndrome; PCI = Percutaneous Coronary Intervention; LD = Loading Dose; MD = Maintenance Dose; NNT = Number Needed to Treat; CV = Cardiovascular

8. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association 0 2 4 6 8 10 12 14 16 18 0306090180270360450 Days Endpoint (%) CV Death / MI / Stroke TIMI Major Non CABG Bleeds 17.0% 12.2% Modified from Wiviott SD et al. Circulation 10-14-2008;118:1626-1636 TRITON: Diabetes Subgroup - Prasugrel 30% n = 3146 ACS (STEMI or NSTE ACS) & Planned PCI PRASUGREL 2.6% 2.5% CLOPIDOGREL HR: 0.70 p <0.001 NNT 21 ACS = Acute Coronary Syndrome; STEMI = ST-elevation Myocardial Infarction; NSTE ACS = Non-ST-elevation Acute coronary Syndrome; PCI = Percutaneous Coronary Intervention; LD = Loading Dose; MD = Maintenance Dose; NNT = Number Needed to Treat; CV = Cardiovascular

9. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Days after Randomisation 0 60 120180240300360 12 11 10 9 8 7 6 5 4 3 2 1 0 Cumulative incidence (%) 9.8% 11.7% TICAGRELOR Modified: Wallentin et al. New Eng J Med 2009; 361(11): 1045-1057 PLATO Study: Ticagrelor vs. Clopidogrel n = 18,624 ACS CLOPIDOGREL NNT = 56 HR: 0.84 (0.77-0.92) p <0.001 CV Death / MI / Stroke ACS = Acute Coronary Syndrome; PCI = Percutaneous Coronary Intervention; NNT = Number Needed to Treat; CV=Cardiovascular

10. Dual Anti-platelet Therapy in Patients with DM and ACS Prasugrel if About to undergo PCI Clopidogrel-naïve <75 yrs of age >65 kg weight No history of stroke OR RATHER THAN Ticagrelor if Clopidogrel to further reduce ischemic events No history of hemorrhagic stroke No extreme bradycardia guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association

11. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association ClopidogrelPrasugrelTicagrelor Dosing Oral, once daily Oral, twice daily Onset2-6 hours<1 hour VariabilityHighLow ReversibleNo Yes Plt Inhibition~ 50%70% at 1 hr95% at 2hrs Comparison of Anti-platelet Therapies

12. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Glycemic Control Among Patients with ACS Hyperglycemia during the first 24 to 48 hours after admission  ↑ early mortality in patients with ACS Evidence to support treatment of elevated blood glucose after ACS = inconclusive Patients with acute MI and blood glucose (BG) on admission of >11 mmol/L  likely benefit from maintaining BG 7.0 -10.0 mmol/L – Insulin therapy may be required – Helpful to have protocols

13. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Recommendation 1 1.Patients with ACS should be screened for diabetes with a fasting plasma glucose, A1C or 75 gram OGTT prior to discharge from hospital. [Grade D consensus] 2013

14. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Recommendation 2 2.All patients with diabetes and ACS should receive the same treatments that are recommended for patients with ACS without diabetes since they benefit equally [Grade D, consensus].

15. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Recommendation 3 3.Patients with diabetes and ACS undergoing PCI should receive antiplatelet therapy with prasugrel (if clopidogrel-naïve, 65kg and no history of stroke) [Grade A, Level 1] or ticagrelor [Grade B, Level 1], rather than clopidogrel, to further reduce recurrent ischemic events. Patients with DM and non-STE ACS and higher risk features, destined for a selective invasive strategy should receive ticagrelor, rather than clopidogrel [Grade B level 2] 2013

16. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Recommendation 4 4. Patients with diabetes and non-STE ACS and high risk features should receive an early invasive strategy rather than a selective invasive approach to revascularization to reduce recurrent coronary events, unless contraindicated [Grade B Level 2]. 2013

17. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Recommendation 5 5.In patients with diabetes and STE-ACS, the presence of retinopathy should not be a contraindication to fibrinolysis [Grade B, Level 2].

18. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Recommendation 6 6.In-hospital management of diabetes in ACS should include strategies to avoid both hyperglycemia and hypoglycemia: – Blood glucose should be measured on admission and monitored throughout the hospitalization [Grade D, Consensus] – Patients with acute MI and blood glucose on admission of >11 mmol/L may receive glycemic control in the range of 7.0 to 10.0 mmol/L followed by strategies to achieve recommended glucose targets long term [Grade C, Level 2]

19. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Recommendation 6 (continued) 6.In-hospital management of diabetes in ACS should include strategies to avoid both hyperglycemia and hypoglycemia: – Insulin therapy may be required to achieve these targets [Grade D, consensus]. A similar approach may be taken in those with diabetes and admission blood glucose <11.0 mmol/L [Grade D, consensus] – An appropriate protocol should be developed and staff trained to ensure the safe and effective implementation of this therapy and to minimize the likelihood of hypoglycemia [Grade D, Consensus].

20. CDA Clinical Practice Guidelines www.guidelines.diabetes.cawww.guidelines.diabetes.ca – for professionals 1-800-BANTING (226-8464) www.diabetes.ca www.diabetes.ca – for patients guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association