PROTECTING YOUR SWEET HEART

Transcription

1 PROTECTING YOUR SWEET HEART Cardiovascular risk reducdon in diabetes too many choices and so much confusion! Dr. Arden Barry, BSc, BSc(Pharm), PharmD, ACPR Clinical Pharmacy and Research Specialist, Chilliwack Primary Care Clinic, Lower Mainland Pharmacy Services Assistant Professor (Partner), Faculty of PharmaceuDcal Sciences, University of BriDsh Columbia

2 NO COI

3 ObjecDves 1. Review the CV risk assessment tools for padents with DM; 2. Review the effect of intensive glycemic control on CV outcomes in padents with DM; 3. Review CV outcomes associated with individual andhyperglycemic agents with a focus on DPP- 4 inhibitors; 4. Review other CV risk reducdon strategies in padents with DM including lipid- lowering therapy, andplatelet agents and BP control.

4 380 MILLION 6 TO 7 YEARS DOUBLE TROUBLE Lancet 2014;383:

5 CV RISK

6 CV Risk Risk calculators: Framingham Risk Score UKPDS Risk Engine ASCVD Risk EsDmator High- risk DM padents: Macrovascular disease Age 40 >15 yr duradon and age 30 Microvascular disease Can J Cardiol 2013;29:151-67

7 forms

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9 hjp://chd.bestsciencemedicine.com/calc2.html

10 A1c AND CV RISK

11 CONTROL Meta- analysis of 4 trials (ACCORD, ADVANCE, UKPDS, VADT) N = 27,049 Follow- up: 4.4 yr Diabetologia 2009;52:

12 CONTROL Major CV events More- intensive Less- intensive HR 95% CI Severe hypoglycemia (no) Diabetologia 2009;52:

13 CDA Guidelines Can J Diabetes 2013;37(suppl 1):S1- S212

14 HOW TO LOWER A1c

15 CDA Guidelines Melormin as inidal therapy for all padents Can J Diabetes 2013;37(suppl 1):S1- S212 Lancet 1998;352:854-65

16 SPREAD- DIMCAD Design PopulaEon IntervenEon Control MC, R, DB T2DM with CAD Melormin 500 mg PO Dd Glipizide 10 mg PO Dd 1 outcome All- cause death, CV death, nonfatal MI, nonfatal stroke, arterial revascularizadon Follow- up 5 yr Diabetes Care 2013;36:

17 SPREAD- DIMCAD N = 304 MeLormin Glipizide HR 95% CI 1 outcome (%) All- cause death (%) NSS Hypoglycemia (%) NSS Diabetes Care 2013;36:

18 CDA Guidelines Other andhyperglycemic agents should be added to melormin if glycemic targets are not met, taking into account the following: Can J Diabetes 2013;37(suppl 1):S1- S212

19 AnDhyperglycemics Acarbose DPP- 4 inhibitors GLP- 1 receptor agonists Insulin MegliDnides Sulfonylureas Thiazolidinediones

20 Rosiglitazone N Engl J Med 2007;356: Arch Intern Med 2010;170:

21 Rosiglitazone Meta- analysis of 56 trials N = 35,531 OR 95% CI MI CV death Arch Intern Med 2010;170:

22 Pioglitazone Design PopulaEon IntervenEon Control MC, R, DB, PC T2DM with macrovascular disease Pioglitazone 45 mg PO daily Placebo 1 outcome All- cause death, ACS, stroke, coronary/peripheral endovascular/surgical intervendon, above- ankle amputadon Follow- up 2.9 yr Lancet 2005;366:

23 Pioglitazone N = 5,238 All- cause mortality, nonfatal MI, stroke (%) Pioglitazone Placebo HR 95% CI Lancet 2005;366:

24 Insulin Glargine Design R, MC, OL PopulaEon Age 50 with T2DM, IFG or IGT IntervenEon Insulin glargine SC daily to target FBG 5.3 mmol/l Control Standard care 1 outcome CV death, nonfatal MI, nonfatal stroke Follow- up 6.2 yr N Engl J Med 2012;367:319-28

25 Insulin Glargine N = 12,537 Insulin Standard p Severe hypoglycemia (no/100- person yr) <0.001 N Engl J Med 2012;367:319-28

26 Sulfonylureas Cochrane Database Syst Rev 2013;4:CD009008

27 Sulfonylureas Meta- analysis of 72 trials N = 22,589 DuraDon: 24 wk 10.7 yr Second- generaeon sulfonylureas Comparator All- cause mortality CV mortality Nonfatal MI Placebo - - Melormin Insulin MegliDnides NSS NSS NSS IncreDn- based intervendons Cochrane Database Syst Rev 2013;4:CD009008

28 DPP- 4 Inhibitors Inhibit endogenous degradadon of GLP- 1 Lower A1c by % Low propensity to cause hypoglycemia Weight- neutral Available agents: aloglipdn, linaglipdn, saxaglipdn and sitaglipdn CV outcome trials: SAVOR- TIMI 53, EXAMINE Ann Pharmacother 2013;47:

29 SAVOR- TIMI 53 Design MC, R, DB, PC PopulaEon T2DM with or at risk for CVD IntervenEon SaxaglipDn 5 mg PO daily (2.5 mg PO daily if egfr 50 ml/min) Control Placebo 1 outcome CV death, MI, ischemic stroke Follow- up 2.1 yr N Engl J Med 2013;369:

30 SAVOR- TIMI 53 Baseline characterisecs N 16,492 A1c (%) 8.0 Age (yr) 65 egfr 50 ml/min (%) 16 Male (%) 67 Melormin (%) 70 HTN (%) 82 ASA (%) 75 ASCVD (%) 79 ACEI/ARB (%) 82 Dyslipidemia (%) 71 StaDn (%) 78 Non- inferiority analysis 1.30 SaxaglipDn bejer Placebo bejer N Engl J Med 2013;369:

31 SAVOR- TIMI 53 N Engl J Med 2013;369:

32 SAVOR- TIMI 53 SaxaglipEn Placebo HR 95% CI All- cause death (%) CV death (%) MI (%) NSS Ischemic stroke (%) HF hospitalizadon (%) SaxaglipEn Placebo p Hypoglycemia (%) <0.001 Renal abnormality (%) Skin reacdon (%) PancreaDDs (%) NSS N Engl J Med 2013;369:

33 EXAMINE Design PopulaEon MC, R, DB, PC T2DM with ACS within days IntervenEon AloglipDn 25 mg PO daily (12.5 mg PO daily if egfr ml/ min, 6.25 mg PO daily egfr <30 ml/min) Control Placebo 1 outcome CV death, nonfatal MI, nonfatal stroke Follow- up 1.5 yr N Engl J Med 2013;369:

34 EXAMINE Baseline characterisecs N 5,380 A1c (%) 8.0 Age (yr) 61 egfr <60 ml/min (%) 29 Male (%) 68 Melormin (%) 66 HTN (%) 83 ASA (%) 91 Prior MI (%) 88 ACEI/ARB (%) 82 Index MI (%) 77 StaDn (%) 90 Non- inferiority analysis 1.30 AloglipDn bejer Placebo bejer N Engl J Med 2013;369:

35 EXAMINE N Engl J Med 2013;369:

36 EXAMINE AloglipEn Placebo HR 95% CI All- cause death (%) CV death (%) Nonfatal MI (%) NSS Nonfatal stroke (%) AloglipEn Placebo p Hypoglycemia (%) Renal dialysis (%) NSS Acute pancreadds (%) HF hospitalizadons and skin reacdons not reported N Engl J Med 2013;369:

37 DPP- 4 Inhibitors Meta- analysis of 50 trials N = 55,141 Mean intervendon Dme: 45.3 wk Cardiovasc Ther 2014;32:147-58

38 DPP- 4 Inhibitors DPP- 4 inhibitor vs comparator: RR 95% CI All- cause mortality CV mortality ACS Stroke HF outcomes HF hospitalizadon Cardiovasc Ther 2014;32:147-58

39 DPP- 4 Inhibitors Meta- analysis of 60 studies N = 353,639 Raw event rate: 0.11% Risk of pancreadds: OR 1.11 (95% CI ) Did not include SAVOR- TIMI 53 or EXAMINE BMJ 2014;348:g2366

40 DPP- 4 Inhibitors hjp:// sc.gc.ca/dhp- mps/medeff/bulledn/carn- bcei_v24n4- eng.php

41 AnDhyperglycemics Ongoing CV outcomes trials: BI CANVAS CAROLINA CARMELINA DECLARE- TIMI 58 DEVOTE ELIXA Ertugliflozin EXSCEL ITCA650 LEADER MK REWIND SUSTAIN6 TECOS TOSCA IT Lancet 2014;383:

42 WHAT ELSE?

43 StaDn Design MC, R, DB, PC PopulaEon T2DM IntervenEon AtorvastaDn 10 mg PO daily Control Placebo 1 outcome ACS, coronary revascularizadon, stroke Follow- up 3.9 yr Lancet 2004;364:685-96

44 StaDn N = 2, % vs 9.0% (NNT = 32) HR 0.63 (95% CI ) Lancet 2004;364:685-96

45 ASA Meta- analysis of 6 trials (including POPADAD and JPAD) N = 10,117 Follow- up: yr BMJ 2009;339:b4531

46 ASA ASA vs control/placebo: RR 95% CI All- cause mortality CV mortality Major CV events MI Stroke Any bleeding GI bleeding BMJ 2009;339:b4531

47 BP Control Design MC, R, OL PopulaEon T2DM with CAD or 2 CV risk factors IntervenEon SBP <120 mmhg Control SBP <140 mmhg 1 outcome CV death, nonfatal MI, nonfatal stroke Follow- up 4.7 yr N Engl J Med 2010;362:

48 BP Control N = 4,733 HR 0.88 (95% CI ) SBP <120 mmhg SBP <140 mmhg p Serious adverse events (no) <0.001 Hypotension (no) 17 1 <0.001 Bradycardia (no) N Engl J Med 2010;362:

49 BP Control Meta- analysis of 4 trials N = 2,580 DBP <85 vs mmhg All- cause mortality: Cochrane Database Syst Rev 2013;10:CD008277

50 CDA Guidelines StaDn therapy for all high- risk padents ASA should not roudnely be used in primary prevendon SBP <130 mmhg and DBP <80 mmhg Can J Diabetes 2013;37(suppl 1):S1- S212

51 STENO- 2 Design PopulaEon R, OL T2DM with microalbuminuria IntervenEon Intensive therapy (A1c <6.5%, TC <4.5 mmol/l, TG <1.7 mmol/l, BP <130/80 mmhg, ACEI/ARB, low- dose ASA) Control ConvenDonal therapy 1 outcome Death from any cause Follow- up 13.3 yr (treatment 7.8 yr + observadon 5.5 yr) N Engl J Med 2008;358:580-91

52 STENO- 2 N = 130/160 All- cause mortality: 30% vs 50% (NNT = 5) HR 0.54 (95% CI ) N Engl J Med 2008;358:580-91

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