A importânciados novos tratamentosadjuvantesda ICP E. Infante de Oliveira

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1 A importânciados novos tratamentosadjuvantesda ICP E. Infante de Oliveira S. Cardiologia I, Hospital Santa Maria, CHLN Instituto de Fisiologia, Faculdade Medicina, UL

2 Disclosure Nothing to disclose unfortunately Menino da Lagrima by Coca-Cola

3 Groundbreaking innovation Wright brothers first flight - December 17, 1903

4 Groundbreaking innovation? Tobacco Smoke Enemas (1750s 1810s) The tobacco enema was used to infuse tobacco smoke into a patient s rectum for various medical purposes, primarily in the resuscitation of drowning victims.doubts about the credibility of tobacco enemas led to the popular phrase blow smoke up your ass.

5 15 minutes is not infinity Arman, Alarm Clocks (Reveils), Collection Museum of Contemporary Art, Chicago. Photo: Nathan Keay, MCA Chicago.

6 Time, options& compromise New oral antiplatelets Direct thrombin inhibitors Myocardial conditioning "The bad news is time flies. The good news is you're the pilot. Michael Altshuler

7 New P2Y12 antagonists Faster, greater potency, more predictable and some reversible AntmanEM et al. J Am CollCardiol May 27

8 New P2Y12 antagonists Faster, greater potency, more predictable and some reversible AntmanEM et al. J Am CollCardiol May 27

9 New P2Y12 antagonists Faster, greater potency, more predictable and some reversible AntmanEM et al. J Am CollCardiol May 27

10 New P2Y12 antagonists Faster, greater potency, more predictable and some reversible AntmanEM et al. J Am CollCardiol May 27

11 New P2Y12 antagonists Faster, greater potency, more predictable and some reversible AntmanEM et al. J Am CollCardiol May 27

12 New P2Y12 antagonists Faster, greater potency, more predictable and some reversible AntmanEM et al. J Am CollCardiol May 27

13 New P2Y12 antagonists Faster, greater potency, more predictable and some reversible AntmanEM et al. J Am CollCardiol May 27

14 New P2Y12 antagonists Faster, greater potency, more predictable and some reversible Cannon CP et al. Lancet 2009

15 New P2Y12 antagonists Faster, greater potency, more predictable and some reversible Cannon CP et al. Lancet 2009

16 New P2Y12 antagonists Faster, greater potency, more predictable and some reversible Cannon CP et al. Lancet 2009

17 New P2Y12 antagonists Faster, greater potency, more predictable and some reversible Cannon CP et al. Lancet 2009

18 New P2Y12 antagonists Faster, greater potency, more predictable and some reversible Cannon CP et al. Lancet 2009

19 New P2Y12 antagonists Faster, greater potency, more predictable and some reversible Cannon CP et al. Lancet 2009

20 New P2Y12 antagonists Faster, greater potency, more predictable and some reversible Cannon CP et al. Lancet 2009

21 Direct thrombin inhibitor Bivalirudin sweet spot between efficacy and safety? Trials REPLACE-2 ACUITY ISAR-REACT 3 HORIZONS ARMYDA-BIVALVE

22 Direct thrombin inhibitor Bivalirudin sweet spot between efficacy and safety? REPLACE-2 PCI 6010 patients; bivalirudin plus provisional GPI vs. UFH plus GPI Lincoff M. JAMA 2003

23 Direct thrombin inhibitor Bivalirudin sweet spot between efficacy and safety? REPLACE-2 PCI 6010 patients; bivalirudin plus provisional GPI vs. UFH plus GPI Lincoff M JAMA 2003

24 Direct thrombin inhibitor Bivalirudin sweet spot between efficacy and safety? ACUITY PCI NSTEMI patients with moderate-to-elevated bleeding risk Bivalirudin vs. UFH/LMWH plus GPI Stone G. N EnglJ Med2006

25 Direct thrombin inhibitor Bivalirudin sweet spot between efficacy and safety? ISAR-REACT 3 Elective PCI pre-loading 600 mg clopidogrel; Bivalirudin vs. UFH KastratiA. N EngJ Med 2008

26 Direct thrombin inhibitor Bivalirudin sweet spot between efficacy and safety? HORIZONS 30 days PCI STEMI 3602 patients; Bivalirudin vs. UFH plus GPI Stone GW. N EnglJ Med 2008

27 Direct thrombin inhibitor Bivalirudin sweet spot between efficacy and safety? HORIZONS 30 days PCI STEMI 3602 patients; Bivalirudin vs. UFH plus GPI Stone GW. N EnglJ Med 2008

28 Direct thrombin inhibitor Bivalirudin sweet spot between efficacy and safety? HORIZONS-AMI 3 years PCI STEMI 3602 patients; Bivalirudin vs. UFH plus GPI Stone GW. Lancet 2011

29 Direct thrombin inhibitor Bivalirudin sweet spot between efficacy and safety? ARMYDA-BIVALVE PCI ACS 401 patients with high bleeding risk (age >75; diabetes; CKD) Bivalirudin vs. low-dose UFH (75 IU/Kg) Patti G. ACC 2011

30 Direct thrombin inhibitor Bivalirudin sweet spot between efficacy and safety? EVENT registry PCI 7777 patients; bivalirudin vs. UFH vs. UFH plus GPI 30% composite bleeding reduction vs. UFH monotherapy 57% composite bleeding reduction vs. UFH plus GPI Bangalore et al. Circ Cardiovasc Interv. 2011

31 Myocardial conditioning Is this the way to go or is it just another tobacco smoke enema idea? Ischemia Reperfusion Infarct size reperfusion injury ischemic injury PreC coronary occlusion Postconditioning time Selon Garcia Dorado

32 Myocardial conditioning Is this the way to go or is it just another tobacco smoke enema idea? Zhao ZQ Am J PhysiolHeart Physiol2001

33 Myocardial conditioning Is this the way to go or is it just another tobacco smoke enema idea? Zhao ZQ Am J PhysiolHeart Physiol2001

34 Myocardial conditioning Postconditioning protects the human heart? Occluded coronary artery Reperfusion Control Direct stenting Postcond Balloon inflations - deflations Staat et al. Circulation. 2005;112:

35 Myocardial conditioning Postconditioning protects the human heart? CK release (AUC: arbitrary units) % (p < 0.05) Control Post-Cond 0 Adm. PTCA 4h 8h 24h 48h 72h Reperfusion Staat et al. Circulation. 2005;112:

36 Myocardial conditioning Postconditioning protects the human heart? 3 * 3 Blush grade 2 1 2,5 2 1,5 1 0,5 ST segment shift (mm) 0 C PostC C PostC 0 Staat et al. Circulation. 2005;112:

37 Myocardial conditioning Postconditioning protects the human heart? Lonborg, J. Circ Cardiovasc Interv. 2010;3:34-41.

38 Myocardial conditioning Preconditioning protects the human heart? Elective PCI ctniat 24 hours after and MACCE at six months Blood pressure cuff repeatedly inflated (200 mmhg) and deflated on the upper arm in 5-minute intervals for a total of 3 times Hoole SP et al. Circulation 2009; 119:

39 Myocardial conditioning Preconditioning protects the human heart? Remote ischemic preconditioning increases myocardial salvage during acute MI Blood pressure cuff repeatedly inflated (200 mmhg) and deflated on the upper arm in 5-minute intervals for a total of 4 times End point PCI plus remote conditioning, median (IQR) PCI alone, median (IQR) p Salvage index* 0.75 ( ) 0.55 ( ) Area at risk, % of left ventricle 26 (20 40) 28 (22 42) 0.97 Salvage, % of left ventricle 16 (10 25) 12 (5 23) Final infarct size, % of left ventricle 4 (1 14) 7 (1 21) 0.1 Bøtker HE et al. Lancet 2010; 375:

40 Myocardial conditioning Pharmacological conditioning protects the human heart? Mechanical Conditioning PCI or thrombolysis Pharmacologycal Conditioning adenosine, NO, K + ATPopeners, insulin, survival kinases mptpinhibitors,.. Drug

41 Myocardial conditioning Pharmacological conditioning protects the human heart?

42 Myocardial conditioning Pharmacological conditioning protects the human heart?

43 Myocardial conditioning Pharmacological conditioning protects the human heart?

44 Myocardial conditioning Pharmacological conditioning protects the human heart?

45 Myocardial conditioning Pharmacological conditioning protects the human heart? STEMI < 12 hrs LAD or RCA Ciclosporine A (or saline) 2.5 mg/kg IV bolus 10 min before PCI direct stenting CK / TnIreleaseday1-3 & MRI day CK release Control CsA (UI/L) Piot et al. NEJM 2008;359:473-81

46 Myocardial conditioning Pharmacological conditioning protects the human heart? Does Cyclosporine ImpRove Clinical outcome in ST elevation myocardial infarction CIRCUS - < 12 hrs LAD STEMI Endpoints: all-cause mortality, cardiovascular death, hospitalization for HF, LV remodelling Hospices Civils de Lyon; PI: Michel Ovize Cyclosporine A (or placebo) (2.5 mg/kg, IV bolus) t -10 min t 0 Echo 1M 3M FU 6M Echo 1Y

47 A importânciados novos tratamentosadjuvantesda ICP E. Infante de Oliveira S. Cardiologia I, Hospital Santa Maria, CHLN Instituto de Fisiologia, Faculdade Medicina, UL