Complex CAD (5) PVD-P Valv. CM. Sub-Clinical Arterial (2) DBD/Frailty (2) Health Political (1) Personal (3)

Transcription

1 1. A Transition From Disease to Health 2. Heart Brain Integration 3. Imaging / Omics / Regeneration / Life Style Complex CAD (5) PVD-P Valv. CM AF Sub-Clinical Arterial (2) DBD/Frailty (2) Health Political (1) Personal (3)

2 Revascularization for Coronary Artery Disease Medical vs PCI vs CABG 1980 s. The Rule of 2 / 3 CABG - Moderate <LVEF Severe? (No, STICH) - Severe Ischemia Moderate? (? ISCHEMIA) - 3 Vessel Disease 2vd, Prox LAD? (Yes, CG) 1990 s. The Rule of 2 / 3 PCI? 2010 s. 2020,s. Medical Therapy >, PCI <, CABG > (Diabetes) Anatomical & Ischemic Score - Non Invasive

3 Revascularization for Coronary Artery Disease Medical vs PCI vs CABG 1980 s. The Rule of 2 / 3 CABG - Moderate <LVEF Severe? (No, STICH) - Severe Ischemia Moderate? (? ISCHEMIA) - 3 Vessel Disease 2vd, Prox LAD? (Yes, CG) 1990 s. The Rule of 2 / 3 PCI? 2010 s. 2020,s. Medical Therapy >, PCI <, CABG > (Diabetes) Anatomical & Ischemic Score - Non Invasive

4 COMPLEX CHRONIC CORONARY DISEASE TRIAL MVD DM INTERV. MT. EP.-R SYNTAX FAME BARI COURAGE Data CABG > PCI SYNTAX Score?. PCI? ISCHEMIA Score? CABG / PCI = MT X.OV.ER 42% PCI = MT ISCHEMIA >10% -Events FREEDOM (+) + CABG > PCI No Freedom of Choice? Conclusions Methods-Interests Concerns

5 SYNTAX - CABG Vs PCI - MVD and/or LMD: 5-year Follow-up Of The Randomized SYNTAX (FW Mohr, PW Serruys et. al.) Lancet 2013; 381: 629 SS > 22 MI, DEATH, STROKE REPEAT REVASC. MACCE

6 Syntax Score is purely an anatomic score of the extent of CAD (>50%) in a pt Each lesion is assigned a numerical number and then sum of all lesions score for a patient is calculated to come up with the final numerical Syntax score Pt are divided in 3 groups: Low <22 Intermediate High >32 Sianos, P Serruys et. al. EuroInterv. 2005;1:219. Serruys P et al. NEJM 2009;360:961.

7 Baseline SYNTAX Score Tercile -CABG Cumulative Event Curves For MACCE SYNTAX (FW Mohr, PW Serruys et. al.) Lancet 2013; 381: 629

8 COMPLEX CHRONIC CORONARY DISEASE TRIAL MVD DM INTERV. MT. EP.-R SYNTAX FAME BARI COURAGE Data CABG > PCI SYNTAX Score?. PCI? ISCHEMIA Score? CABG / PCI = MT X.OV.ER 42% PCI = MT ISCHEMIA >10% -Events FREEDOM (+) + CABG > PCI No Freedom of Choice? Conclusions Methods-Interests Concerns

9 Coronary Flow Reserve (CFR) Measures integrated hemodynamic effects of epicardial CAD, diffuse atherosclerosis, vessel remodeling and microvascular dysfunction on myocardial tissue perfusion CFR = MBF peak hyperemia MBF rest VR Taqueti and MF Di Carli 2014

10 FFR As A Surrogate For Inducible Myocardial Ischaemia FAME I (FFR>0.8) - OMT of Non-Isch.Lesions Prevent MI/Death FAME II (FFR<0.8) - PCI of Isch. Lesions Prevent MI/Death TP van de Hoef Nat. Rev. Cardiol. 2013;10:439 FAME 2 (B De Bruyne) NEJM 2014; 371:1208

11 Evolving Concepts Of Angiogram: Fractional Flow Reserve Discordances In 4000 Coronary Stenoses G Toth et. al. Eur Heart J. 2014;35:2831

12 JACC 2014;63: JACC 2014;63:799 - JACC Imag. 2014;7: 1936

13 Impact of CFR Measured by PET on the Prognosis in Diabetic Individuals VL Murthy et. al. Circulation. 2012;126:1858 (Brigham, Boston) S Achenbach et. al. J Am Coll Cardiol Img 2013;6:714 BP., Hgb A1Cc

14 Diabetes M., Prediabetes (N= 9051, x2 on 6yrs, FU14 yrs ) Incidence of Subclinical Myoc. Damage & Clinical Events ARIC (E Selvin et. al.) Circulation 2014;130:1374

15 Proportion of Outcome Events by Achieved SBP - ONTARGET Trial ONTARGET (J Redon et. al.)j ACC2012;59:74 Microvasculature, Underperfusion?

16 Mortality in the ACCORD Population Over a Wide Range of Average On-treatment HbA1c Values ACCORD (MC Riddle et al) Circ 2010;122:844 - Microvascular / Catecholamines?

17 Effects of Intensive Glycaemic Control on Ischaemic Heart Disease: Analysis of Data from the ACCORD Trial We assessed 10,251 adults aged years with 2 diabetes, mean HbA1c 8.3%, and risk factors for CAD enrolled in the ACCORD trial. Participants were assigned to intensive or standard therapy (target HbA1c less than 6.0% or %). We assessed fatal or non-fatal MI, coronary revascularization, unstable angina, and new angina during active treatment (mean 3.7 years) plus a further mean 1.2 years. MI was less frequent in the intensive than in the standard group during active treatment (hazard ratio [HR] 0.80; p=0.015). Findings were similar for combined MI, coronary revascularization, and unstable angina (active treatment HR 0.89) and for coronary revascularization alone (0.84) and unstable angina alone (0.81) during full follow-up. Raised glucose concentration is a modifiable risk factor for CAD in middle-aged people with type 2 diabetes and other CV risk factors. ACCORD (HC Gerstein et al.) Lancet 2014; 384:1936

18 PCI versus CABG in Insulin and Non-Insulin Treated Diabetic Patients: Results from the FREEDOM Trial FREEDOM (GD Dangas, V Fuster et. al.) JACC 2014 (In Press)

19 COMPLEX CHRONIC CORONARY DISEASE TRIAL MVD DM INTERV. MT. EP.-R SYNTAX FAME BARI COURAGE Data CABG > PCI SYNTAX Score?. PCI? ISCHEMIA Score? CABG / PCI = MT X.OV.ER 42% PCI = MT ISCHEMIA >10% -Events FREEDOM (+) + CABG > PCI No Freedom of Choice? Conclusions Methods-Interests Concerns

20 COMPLEX CHRONIC CORONARY DISEASE TRIAL MVD DM INTERV. MT. EP.-R SYNTAX FAME BARI COURAGE Data CABG > PCI SYNTAX Score?. PCI? ISCHEMIA Score? CABG / PCI = MT X.OV.ER 42% PCI = MT ISCHEMIA >10% -Events FREEDOM (+) + CABG > PCI No Freedom of Choice? Conclusions Methods-Interests Concerns

21 COMPLEX CHRONIC CORONARY DISEASE TRIAL MVD DM INTERV. MT. EP.-R SYNTAX FAME BARI COURAGE Data CABG > PCI SYNTAX Score?. PCI? ISCHEMIA Score? CABG / PCI = MT X.OV.ER 42% PCI = MT ISCHEMIA >10% -Events FREEDOM (+) + CABG > PCI NO FREEDOM CHOICE? Conclusions Methods-Interests Concerns

22 Diabetes, Carotid Disease-PET/MRI Inflammatory, Hemorrhagic, Diffuse V Fuster et al., NEJM 1992; 326: :310 Moreno PR.,Fuster V, et al. Circ 2000;102:2180 K-P Purushothaman, V Fuster, PR Moreno, et al.,jacc 2012;60:112- R Corti & V Fuster EHJ 2011 (April 19) JD Spence. Circ. 2013;127:739

23 FREEDOM Design Eligibility: DM patients with MV-CAD eligible for stent or surgery Exclude: Patients with acute ACS, LM Disease, Severe CHF Randomized 1:1 MV-Stenting With Drug-eluting CABG With or Without CPB Primary Outcome: Composite of earliest occurring of: All cause mortality, Non-fatal MI, and Non-fatal Stroke New Engl J Med 2012;367:2375

24 BASELINE CHARACTERISTICS BY TREATMENT ASSIGNMENT Characteristic PCI/DES CABG P-value* No. of Patients Age at randomization yr 63.2 ± ± Male sex 73% 70% 0.08 Body mass index gm/m ± ± Duration of diabetes yrs 10.1 ± ± Hemoglobin A1c - % 7.8 ± ± Current smoker 15% 17% 0.31 Previous myocardial infarction 26% 25% 0.56 Previous stroke 4% 3% 0.31 History of hypertension 85% 85% 0.75 Congestive heart failure 26% 28% 0.25 Hyperlipidemia 84% 83% 0.66 Cath PCI Registry (GJ Dehmer et al.) JACC 2012; 20:2007 Overweight (BMI 25 kg/m2) 79.5 % - Diabetes mellitus 36.2%

25 Death/Stroke/MI, % FREEDOM TRIAL MI / DEATH 1 / STROKE 30 PCI/DES CABG Logrank P= PCI/DES CABG Year Event Rates: 26.6% vs. 18.7% Years Post-randomization New Engl. J. Med. 2012; 367: 2375

26 Stroke, % STROKE 2 Severely Disabling Scale CABG PCI/DES NIH > 4 55% 27% Rankin >1 70% 60% CABG PCI/DES Logrank P= CABG 5.2% 0 PCI/DES 2.4% Years post-randomization PCI/DES N CABG N

27 Freedom from Event (%) PRIMARY ENDPOINT DEATH / STROKE / MI TREATMENT / SYNTAX INTERACTION Freedom from Event (%) Freedom from Event (%) SYNTAX Score 22 (N=669) 5-Year Event Rates: 23.2% 17.2% PCI/DES CABG SYNTAX Score (N=844) 5-Year Event Rates: 27.2% 17.7% PCI/DES CABG Years post-randomization Years post-randomization SYNTAX Score 33 (N=374) 5-Year Event Rates: 30.6% 22.8% PCI/DES CABG Years post-randomization Average SYNTAX Score 26

28 PRE-SPECIFIED SUBGROUP ANALYSES PCI/DES Beneficial CABG Beneficial Treatment x Subgroup Interaction 5-yr Rate (%) PCI/DES CABG ALL SUBJECTS SYNTAX SYNTAX SYNTAX P= Males 1356 Females 544 P= Caucasian 1452 African-American 119 P= Vessel Disease Vessel Disease 1573 LVEF < 40% 32 LVEF 40% 1259 No LAD involved 151 LAD involved 1737 Hx stroke 65 No Hx stroke 1835 Renal insuff. 129 No Renal insuff HbA1c < 7% 630 HbA1c 7% 1119 N. American Site 770 Non-N. American 1130 P=0.75 P=0.37 P=0.83 P=0.57 P=0.62 P=0.99 P= Hazard Ratio for Death/Stroke/MI

29 MEETING TARGETS FOR RISK FACTOR CONTROL? Risk Factors - Proportion of Participants at Goal % 1 year Trials LDL SBP DBP Hb A1C Meet Goals Base FU BARI-2D COURAGE FREEDOM Freedom, Bari-2D, Courage Investigators, JACC 2013;61:1607 PURE (S Yusuf et al.) Lancet 2011; Aug 28 - Poor Countries,7%!!! NHANES, AHA, NHLBI-JNC-7, NHLBI-NCEP P Muntner, V Fuster et al., AHJ 2011; 161: seconds!!!!

30 Conclusion In patients with diabetes and advanced coronary disease, CABG was of significant benefit as compared to PCI. MI & all cause mortality were independently decreased, while stroke was slightly increased No significant interaction between the treatment effect of CABG on the primary endpoint according to SYNTAX score or any other prespecified subgroup. CABG surgery is the preferred method of revascularization for patients with diabetes & multivessel CAD. And long term, it appears Cost-Effective FREEDOM (ME Farkouh, V Fuster et al.) New Engl J Med 2012;367:2375 FREEDOM (EA Magnuson, V Fuster, DJ Cohen et. al.) Circ. 2013;127:820

31 1. Circ Cardiovasc Interv. 2014;7:518

32 2. Plots For Binary Region Indicator - World Vs. Canada/US For Stroke From FREEDOM Trial MJ Domanski, V Fuster et. al (Subm).

33 3. Recommendations for CAD Revascularization To Improve Survival Circulation. 2014;130:1749

34 Specific Recommendations For Revascularization In Patients With Diabetes The Task Force on Myocardial Revascularization of the ESC and the EACTS (S Windecker et. al.) Eur Heart J. 2014;35:2541

35 4. CNIC-F/S*-FERRER POLYPILL, 2ary PREVENTION. FOCUS 1 & 2 Argentina Brazil Paraguay Italy Spain FREEDOM AETNA EU 2020 BIO-EQUIVALENCE PHARMACODINAMIC INTERACTION WITH RAMIPRIL PHARMACODYNAMIC INTERACTION WITH SYMVASTATIN FOOD INTERACTION PHARMACOKINETIC INTERACTION WITH ASPIRIN ASA, Statin, ACE-Inhibitor PHARMACOKINETIC INTERACTION WITH SYMVASTATIN PHARMACOKINETIC INTERACTION WITH RAMIPRIL PHARMACODYNAMIC INTERACTION WITH ASPIRIN Am. H J 2011;162:811 Semin.Thor.Cardiov.Surg 2011;23:24 JACC, 2014-In Press - Approved in 22 Countries * Fuster - Funding: European Community

36 Revascularization for Coronary Artery Disease Medical vs PCI vs CABG 1980 s. The Rule of 2 / 3 CABG - Moderate <LVEF Severe? (No, STICH) - Severe Ischemia Moderate? (? ISCHEMIA) - 3 Vessel Disease 2vd, Prox LAD? (Yes, CG) 1990 s. The Rule of 2 / 3 PCI? 2010 s. 2020,s. Medical Therapy >, PCI <, CABG > (Diabetes) Anatomical & Ischemic Score - Non Invasive

37 Future For PCI & CABG Procedure PCI OMT CABG SCAAR (ML Fokkema et.al.) JACC 2013;61: Swedish Registry (VF.Modified)