Il Dr. Giampaolo Niccoli dichiara di non aver ricevuto negli ultimi due anni compensi o finanziamenti da Aziende Farmaceutiche e/o Diagnostiche:

Dichiara altresì il proprio impegno ad astenersi, nell’ambito dell’evento, dal nominare, in qualsivoglia modo o forma, aziende farmaceutiche e/o denominazione commerciale e di non fare pubblicità di qualsiasi tipo relativamente a specifici prodotti di interesse sanitario (farmaci, strumenti, dispositivi medico-chirurgici, ecc.).

Standards of care nel trattamento dell’IMA

Dr. Giampaolo Niccoli

Department of Cardiovascular MedicineCatholic University of the Sacred Heart – Rome

Department of Cardiovascular Sciences

Glycemic disorders in cardiovascular diseases

Lancet 2010;375:2215–22

J Am Coll Cardiol 2004; 43:585-91

LA MALATTIA CORONARIOCA NEL DIABETICO E’ PIU’ SEVERA

LA MALATTIA CORONARIOCA NEL DIABETICO E’ PIU’ ESTESA

Niccoli G et al, EHJ, 2013

LA MALATTIA CORONARIOCA NEL DIABETICO E’ PIU’ VULNERABILE

Niccoli G et al, EHJ, 2013

Diabete: aumentato rischio di mortalità a lungo termine

STEMI

NSTEMI

Piccolo et Al - Effect of Diabetes Mellitus on Frequency of Adverse Events in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention Am J Cardiol 2016;118:345e352

Piccolo et Al - Effect of Diabetes Mellitus on Frequency of Adverse Events in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention Am J Cardiol 2016;118:345e352

Which are the therapeutic objectives in acute phase of ACS in diabetic patients?

1. Glycemic control

2. Antiaggregation

3. Revascularization

1. Glycemic control - 2017 ESC Guidelines on STEMI

2017 ESC Guidelines for the management of acute myocardial infarction in patients presentingwithST-segmentelevation - European Heart Journal (2018) 39, 119–177 doi:10.1093/eurheartj/ehx393

1. Glycemic control - 2015 ESC Guidelines on NSTEMI and 2013 ESC guidelines on diabetes and CVD

2013 ESC guidelines on diabetes

2015 ESC guidelines on NSTEMI

ESC Guidelines on diabetes, pre-diabetes,

and cardiovascular diseases developed in collaboration with the

EASD - European Heart Journal (2013) 34, 3035–

3087 doi:10.1093/eurheartj/e

ht108

2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting

without persistent ST-segment elevation - European Heart Journal

(2016) 37, 267–315 doi:10.1093/eurheartj/ehv320

2015

Suscettibilita’ all’ostruzione microvascolare Predisposizione acquisita

(Timmer et al, AJC, 2005)

(Iwakura et al, JACC, 2003)

Diabetes and acute hyper-glycaemia

Which are the therapeutic objectives in acute phase of ACS in diabetic patients?

1. Glycemic control

2. Antiaggregation

3. Revascularization

2. Antiaggregation (and DM)

Patti and al. -Antiplatelet Therapy in DM - Circulation Journal Vol.78, January 2014

)

18624 patients with ST-segment elevation or non-ST-segment elevation ACS. Among them 4662 (25%) were reported as having DM by the investigators

European Heart Journal (2010) 31, 3006–3016

Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562) (J Am Coll Cardiol 2016;67:2732–40)

Circulation. 2008;118:1626-1636

13 608 subjects eligible for enrollment if they had moderate- to high-risk unstable angina (UA/NSTEMI), after medical treatment for STEMI with coronary anatomy known to be suitable for PCI, or before cardiac catheterization with planned primary PCI for STEMI

Circulation. 2008;118:1626-1636

Circulation. 2016;133:1772-1782. DOI: 10.1161/CIRCULATIONAHA.115.016783

Which are the therapeutic objectives in acute phase of ACS in diabetic patients?

1. Glycemic control

2. Antiaggregation

3. Revascularization

SYNTAX Trial: Death, Stroke and Myocardial infarction

Kappetein et al. EJCTS 2013

Huang et al. CARDIOLOGY 2014, Harskamp et al. Cardior Ther. 2013

The probability of several DES and BMSproducing the best outcomes in termsof efficacy and safety endpoints forpatients with diabetes.

Harskamp et al. Cardior Ther. 2013

Optimal Choice of Stent Type in Diabetic Patientswith Coronary Artery Disease

BMS(bare metal stent)

ZES(Zotarolimus-eluting stent)

PES(Paclitaxel-eluting

stent)

SES(Sirolimus-eluting

stent)

EES(Everolimus-eluting stent)

Conclusions

- A large part of patients presenting with NSTEMI-ACS and STEMI is affected by diagnosed or undiagnosed diabetes mellitus.

- A correct management of many factors in the acute phase of ACS, like correction of hyperglicemia, use of appropriate antiaggregation and a correct choice of revascularization can have an important impact on prognosis

- Discharge tehrapy should be probably tailored in diabetics including prolonged DAPT and new antglycemic drugs with cardioprotective outcome data

Thanks for your attention

Department of Cardiovascular Sciences

ESC guideline son myocardial revascularization: recommendations in diabetics

EHJ 2014

Huang et al. CARDIOLOGY 2014, Harskamp et al. Cardior Ther. 2013

Current evidence for optimal revascularizationstrategy in the diabetes patients ; RCT

3. Revascularization – 2013 ESC guidelines on diabetes,prediabetes and CVD

ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD - European Heart Journal (2013) 34, 3035–3087 doi:10.1093/eurheartj/eht108

3. Revascularization – 2015 ESC guidelines on NSTEMI

2015 ESC Guidelines for the management of acute coronary syndromes in

patients presenting without persistent ST-segment

elevation - European Heart Journal (2016) 37, 267–315

doi:10.1093/eurheartj/ehv320

Freedom Trial

CONCLUSION

- In patients with diabetes and advanced coronary disease,CABG was of significant benefit as compared to PCI. MI & allcause mortality were independently decreased, while strokewas slightly increased

- There was no significant interaction between the treatmenteffect of CABG on the primary endpoint according to SYNTAXscore or any other prespecified subgroup.

- CABG surgery is the preferred method of revascularization for patients with diabetes & multi-vessel CAD

Farkouh ME, et al. N Engl J Med.2012 Dec 20;367(25):2375-84

J Am Coll Cardiol 2010;55:432–40

2. Antiaggregation- 2015 ESC Guidelines on NSTEMI and 2017 ESC focused update on dual antiplatelet therapy

2015 ESC Guidelines for the management of acute coronary syndromes in patients

presenting without persistent ST-segment elevation - European Heart Journal (2016) 37,

267–315 doi:10.1093/eurheartj/ehv320

2017 ESC focused update on dual antiplatelet therapy n coronary artery disease developed in collaboration with EACTS - European Heart Journal (2018) 39, 213–254 doi:10.1093/eurheartj/ehx419

Circulation 2011; 123:798-813

2. Antiaggregation (and DM)

Patti and al. -Antiplatelet Therapy in DM - Circulation Journal Vol.78, January 2014

n engl j med 360;13 nejm.org march 26, 2009

Glycaemic control in acute coronary syndromes:prognostic value and therapeutic options

De Caterina et al- European Heart Journal (2010) 31, 1557–1564 doi:10.1093/eurheartj/ehq162 n engl j med 360;13 nejm.org march 26, 2009

Glycaemic control in acute coronary syndromes:prognostic value and therapeutic options

De Caterina et al- European Heart Journal (2010) 31, 1557–1564 doi:10.1093/eurheartj/ehq162

DIGAMI – 1 . 620 patients with DM and acute MI to a ≥24-h insulin –glucose infusion, followed by multi-dose insulin, or to routine glucose- lowering therapy.326 Mortality after 3.4 years was 33% in the insulin group and 44% (P 1⁄4 0.011) in the control group

DIGAMI 2 failed to demonstrate prognostic benefits.

1. Glycemic control – DIGAMI 1 and DIGAMI 2

What about the prognosis of patients with diabetes after AMI ?

Donahoe Sean M. et al- Diabetes and Mortality Following Acute Coronary Syndromes - JAMA, August 15, 2007—Vol 298, No. 7

Cumulative Incidence of All-Cause Mortality Through 1 Year After ACS

Donahoe Sean M. et al- Diabetes and Mortality Following Acute Coronary Syndromes - JAMA, August 15, 2007—Vol 298, No. 7

Introduction (1)

• Acute coronary syndromes (NSTE-ACS and STE-ACS) represent the main manifestationof ischemic heart desease, the most frequent cause of morbidity and mortality inEurope and worldwide.

• However in Europe there has been an overall trend for a reduction in ischaemic heartdisease mortality over the past three decade ischaemic heart disease now accountsfor almost 1.8 million annual deaths, or 20% of all deaths in Europe.

European Society of Cardiology: Cardiovascular Disease Statistics 2017 European Heart Journal (2017) 0, 1–72

Female Male

1. Standards of Medical Care in Diabetes 2018 Diabetes Care 2018;41(Suppl. 1):S86–S104 | https://doi.org/10.2337/dc18-S009

2. Piccolo et Al - Effect of Diabetes Mellitus on Frequency of Adverse Events in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention Am J Cardiol 2016;118:345e352

3 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation – Web Addenda

- Atherosclerotic cardiovascular disease is the leading cause of morbidity and mortality for individuals with diabetes and is the largestcontributor to the direct and indirect costs of diabetes1.

- Myocardial infarction represents the most common diabetes-relatedcomplication2.

- About 20-30% of European patients with NSTEMI-ACS have knowndiabetes mellitus; but a similar proportion of people may haveundiagnosed diabetes or impaired glucose tolerance3.

Introduction (2)

Glycemic disorders in cardiovascular diseases

State of the Art in Diabetes Management Lars Rydén Department of Medicine Karolinska Institutet Stockholm, Sweden –World Diabetes Day 14° November 2017

Diabetes and pathogenesis of CVD

ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD - European Heart Journal (2013) 34, 3035–3087 doi:10.1093/eurheartj/eht108

Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: full text - European Heart Journal Supplements (2007) 9 (Supplement C), C3–C74 doi:10.1093/eurheartj/ehl261

Which are the therapeutic objectives after discharge indiabetic patients with recent ACS?

1. Risk factors control and CV therapy

2. Use of antidiabeticdrugs with evidence of CV benefits

1. Risk factor control – 2013 ESC guidelines on diabetes,prediabetes and CVD

ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD - European Heart Journal (2013) 34, 3035–3087 doi:10.1093/eurheartj/eht108

1. Risk factor control - Glycemic ControlImpact of intensive vs. conventional glucose-lowering therapy

Significant improvement in end-stage renal disease was observed but no other difference in other microvascular end points. †Diabetes-related mortality

ACCORD, Action to Control Cardiovascular Risk in Diabetes; ADVANCE, Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation; CV, cardiovascular; HbA1c, glycosylated haemoglobin; N/R, not reported;

UKPDS, UK Prospective Diabetes Study; VADT, Veteran’s Affairs Diabetes Trial1. UKPDS Group. Lancet 1998;352:837–853; 2. Holman et al. N Engl J Med 2008;359:1565–1576; 3. Gerstein et al. N Engl J Med

2008;358:2545–2559; 4. ACCORD study group Diabetes Care 2016;39:701–708; 5. Patel et al. N Engl J Med 2008;358:2560–2572; 6. Zoungas et al. N Engl J

Med 2014;371:1392–1406; 7. Duckworth et al. N Engl J Med 2009;360:129–139; 8. Hayward et al. N Engl J Med 2015;372:2197–2206

n engl j med 358;6 www.nejm.org february 7, 2008

n engl j med 358;6 www.nejm.org february 7, 2008

Gæde P et al Diabetologia 2016;59:2298‒2307.

Cardiovascular therapy

Which are the therapeutic objectives after discharge indiabetic patients with recent ACS?

1. Risk factors control and CV therapy

2. Use of antidiabeticdrugs with evidence of CV benefits

Conclusions

Cardiovascular Disease and RiskManagement: Standards of Medical Care in Diabetesd2018 Diabetes Care 2018;41(Suppl. 1):S86–S104

| https://doi.org/10.2337/dc18-S009

n engl j med 373;22 nejm.org November 26, 2015

CANVAS/CANVAS-R

HR and 95% CI were estimated using Cox regression models with stratification according to trial and history of CVD for all canagliflozin groups combined versus placebo. CI, confidence interval; CV, cardiovascular; CVD, cardiovascular

disease; HF, heart failure; HR, hazard ratio; MI, myocardial infarction; PY, person-years; SGLT-2i, sodium-glucose cotransporter-2 inhibitor

Neal B et al. N Engl J Med 2017; doi: 10.1056/NEJMoa1611925

n engl j med 375;4 nejm.org July 28, 2016

n engl j med 375;19 nejm.org November 10, 2016

CI, confidence interval; CV, cardiovascular; MACE, major adverse cardiac event; MI, myocardial infarction

1. Marso SP et al. N Engl J Med 2016;375:311–322; 2. Marso SP et al. N Engl J Med 2016;375:1834–1844; 3. Zinman B et al. Cardiovasc Diabetol 2014;13:102; 4. Neal B et al. N Engl J Med 2017; doi:

10.1056/NEJMoa1611925

2016 European Guidelines on cardiovascular disease prevention in clinical practice

European Heart Journal (2016) 37, 2315–2381