Presentation on theme: "The bitter fate of acute coronary syndrome in diabetics: diabetics have more adverse outcomes after PCI Sergio Berti Fondazione CNR-Reg. Toscana G. Monasterio."— Presentation transcript:
1 The bitter fate of acute coronary syndrome in diabetics: diabetics have more adverse outcomes after PCISergio BertiFondazione CNR-Reg. Toscana G. MonasterioOspedale del Cuore, Massa
2 Diabetes in 2000 and forecast for 2030 500400Prevalenza mondiale (%)300forecast200100Wild S et al. Diabetes Care 2004; 27:
3 Diabetes in 2000 and forecast for 2030 Hossain P et al. N Engl J Med 2007; 356:
4 Early mortality of diabetic and non-diabetic patients with acute myocardial infarction: Historical perspective
5 UA/NSTEMI Diabetes CVD(+) Diabetes CVD(-) No Diabetes CVD(+) 69 Hosp PtsIl registro OASIS (Organization to Assess Strategies for Ischemic Syndromes)7 ha raccolto in maniera prospettica i dati relativi ai pazienti con angina instabilee IMA non Q, seguiti per 2 anni in 6 differenti paesi occidentali e in 69 centri ospedalieri. Degli 8013 pazienti oggetto dell’osservazione, il 21% (n = 1718)aveva una storia clinica di diabete mellito in trattamento dietetico o farmacologico (ipoglicemizzanti orali o insulina). I soggetti diabetici sono stati più spesso sottoposti a interventi di rivascolarizzazione chirurgica (23 vs 20%, p < 0.001), mentre le angiografie coronariche e l’angioplastica sono risultate ovrapponibili nei due gruppi. Il diabete si è confermato associato a un incremento significativo di mortalità globale e mortalità per cause cardiovascolari, ictus e scompenso cardiaco, sia nella fase intraospedaliera che durante l’intero follow- up. I pazienti diabetici hanno inoltre richiesto una permanenza media in ospedale superiore a quella dei soggetti non diabetici (11.4 ± 8 vs 10.3 ± 8 giorni, p < )OASIS RegistryMalmberg K et al,Circulation 2000;102:1014
6 Diabetes and Mortality Following Acute Coronary Syndromes Sean M Diabetes and Mortality Following Acute Coronary Syndromes Sean M. Donahoe, MD at al. JAMA. 2007;298(7):
7 Pooled TIMI Trials 11 study del TIMI group 62036 pts Sean M. Donahoe, MD at al. JAMA. 2007;298(7):
8 Cumulative Incidence of All-Cause Mortality Through 1 Year After ACS Sean M. Donahoe, MD at al. JAMA. 2007;298(7):
9 Cumulative Incidence of All-Cause Mortality Through 1 Year After ACS 30 days8.5%5.4%2.1%1.1%Sean M. Donahoe, MD at al. JAMA. 2007;298(7):
10 Cumulative Incidence of All-Cause Mortality Through 1 Year After ACS 13.2%8.1%7.2%3.1%Sean M. Donahoe, MD at al. JAMA. 2007;298(7):
14 Heart Hospital: STEMI network: Door to balloon Andamento del tempo tra insorgenza del dolore e angioplstica DtB sta per door to balloon (angioplastica)
15 Heart Hospital: STEMI network: 1 year follow-up mortality È l’andamento della mortalità ad un anno, circa il 7%, è un effetto della DIA precedente, riducendo i tempi di intervento migliora la mortalità
16 Patients presenting with STEMI our experience (1496 pts) *Mettere il numero di pazienti totali inseriti nel DB1518 totale293 diabetici1214 non diabetici (54 diabetici +74 prediabed= 128)Definizione di Prediabete LG esc Hb glicata tra 6-6,49 per gli americani tra 5,7 e 6,49*= HbA1c 6>x<6.49
17 Overall Mortality Patients presenting with STEMI our center experience DM-DM+Survival, %Se si riesce modificare il le curve di sopravvivenza con inviato nella precedente mail (perché i pazienti nel DB sono circa 1500 e ne compaiono meno di 1000?Log rank, p<0.001Follow-up, days
18 Overall Mortality Patients presenting with STEMI our center experience DM-*Pre-diabetesDM+Survival, %Se si riesce modificare il le curve di sopravvivenza con inviato nella precedente mailLog rank, p<0.001 for both comparisonsFollow-up, days*= HbA1c 6>x<6.49
19 …Worst outcome… WHY ?Widespread and more aggressive atherosclerotic disease in patients with DiabetesLower response to the antiaggreganting agentsGreater incidence of the “No reflow” phenomenonComorbiditiesLess aggressive treatment strategies in diabetic patients
20 Angiographic data in patients with and without Diabetes presenting with ACS All ACSP value < 0.001Sean M. Donahoe, MD at al. JAMA. 2007;298(7):
21 Angiographic data in patients with and without Diabetes presenting with ACS UA/NSTEMIP value < 0.001Sean M. Donahoe, MD at al. JAMA. 2007;298(7):
22 Angiographic data in patients with and without Diabetes presenting with ACS STEMI**P value < 0.001*P value 0.02Sean M. Donahoe, MD at al. JAMA. 2007;298(7):
23 Mechanisms contributing to platelet dysfunction In patients with diabetes mellitus HYPERGLYCAEMIAIncreased P-selectinexpressionOsmotic effectActivation of PKCDecreased membrane fluidity by glycation of surface proteinsDEFICIENT INSULINACTIONImpaired response toNO and PGI2IRS-dependent factors:Increased intracellular Ca++ degranulationASSOCIATEDMETABOLICCONDITIONSObesityDyslipidemiaInflammationOTHER CELLULARABNORMALITIESPLATELETENDOTHELIALDYSFUNCTIONIncreased platelet turnoverUpregulation of P2Y12 signallingIncreased intracellular Ca++Oxydative stressIncreased P-selectin andGP expressionIncreased production of TFDecreased NO and PGI2 productionPKCIRS-1Ca++P2Y12H2OADPROS/NOSFigure 1. Mechanisms involved in platelet dysfunction in patients with DM. Several mechanisms contribute to platelet dysfunction in diabetes mellitus (DM) patients, including hyperglycemia, insulin deficiency, associated metabolic conditions, and other cellular abnor- malities. Hyperglycemia may increase platelet reactivity by inducing P-selectin (a surface adhesion protein) expression, glycating plate- let surface proteins (decreasing membrane fluidity and, thus, increasing platelet adhesion), and activating protein kinase C (PKC; a mediator of platelet activation) and as a result of the osmotic effect of glucose. Insulin deficiency also contributes to platelet dysfunc- tion by different mechanisms. Some have been suggested to be IRS dependent such as the increase in intracellular calcium concentra- tion, which leads to enhanced platelet degranulation and aggregation. Other factors associated with insulin resistance are not depen- dent on IRS, eg, the impaired response to NO and PGI2, which enhances platelet reactivity. Some metabolic conditions frequently associated with DM may play a role in platelet hyperreactivity, including obesity, dyslipidemia, and enhanced systemic inflammation. In addition to being associated with insulin resistance, obesity contributes to platelet dysfunction, mainly in terms of adhesion and activa- tion, with factors like augmented cytosolic calcium concentration and increased oxidative stress. Abnormalities of the lipid profile, especially hypertriglyceridemia, also affect platelet reactivity by different mechanisms, which include inducing endothelial dysfunction. The presence of endothelial dysfunction is another characteristic feature associated with DM, which enhances platelet reactivity by decreasing the production of NO and PGI2 and contributes to a prothrombotic state through increased production of tissue factor (TF). Other platelet abnormalities present in DM patients can enhance platelet adhesion and activation, including increased expression of surface proteins (P-selectin and GP IIb/IIIa), augmented cytosolic calcium concentration, upregulation of certain pathways like P2Y12 signaling, increased platelet turnover, and oxidative stress, which causes an impairment in platelet function as a result of overproduc- tion of reactive oxygen (ROS) and nitrogen species (NOS).TFNOPGI2Endothelial cellsFerreiro JL, Angiolllo DJ. Circulation 2011; 123:23
24 Diabetes and Clopidogrel Angiolillo DJ et al Diabetes 2005; 54:2430-5Angiolillo DJ J Am Coll Cardiol 2006; 48:
25 Diabetes and Prasugrel TRITON TIMI 38 Tale problematica (resistenza a antiaggreganti) vede una, per lo meno parziale, soluzione nei nuovi antiaggreganti PRASUGREL (Triton timi 38) e..Wiviott SD Circulation 2008;118;
26 PLATO diabetes: All-cause mortality 108642[James 2010:H,I]DiabetesTicagrelor (n=2326)Clopidogrel (n=2336)HR (95% CI) = 0.82(0.66–1.01)8.7%7.0%p for interaction = 0.66All-cause mortality (%)5.0%3.7%No diabetesTicagrelor (n=6999)Clopidogrel (n=6952)HR (95% CI) = 0.77(0.65–0.91)Days after randomisationAll-cause mortality benefit with ticagrelor was consistent with the overall PLATO trial results[Wallentin 2009:J]No interaction between diabetes status and treatment was observed (p=0.66)[James 2010:G,H]CI, confidence interval; HR, hazard ratio.James S, et al. Eur Heart J 2010;31:3006–3016.
27 The “no reflow” phenomenon Multivariable Predictors of the No-Reflow PhenomenonIwakura et al. JACC Vol. 41, No. 1, 2003 January 1, 2003:1–7
28 The “no reflow” phenomenon Myocardial Blush GradeIncidence %Abhiram Prasad, MD at al. ACC Vol. 45, No. 4, 2005 February 15, 2005:508–14
30 Under utilization of an early invasive treatment strategy in diabetic patients with ACS A nationwide studyN= pts.The present study was performed to evaluate if diabetic patients with ACS are offered coronary angiography (CAG) and revascularisation to the same extent as patients without diabetes.The study is a prospective observational nationwide cohort study linking Danish national registers containing information on hospitalisation, revascularisation procedures, claiming of drug prescriptions, and coronary pathology revealed by CAG.The cohort comprises all patients hospitalized with ACS (both STEMI, non-STEMI and UAP) for the first time in Patients discharged or not surviving the day of admission were excluded.Patients were followed for 60 days.Diabetes was defined as claiming of a prescription of insulin and/or oralhypoglycaemic agents within 6 months prior to the ACS event.Information on comorbidity, medicine use, socioeconomic status and vital status was available for each patient. From the Danish Heart Registry invasive procedures (CAG) were identified.Cox proportional-hazard models were used to estimate the difference in the rate of CAG and subsequent revascularization (PCI or CABG) within 60 days of the admission adjusting for explanatory variables.
32 DES vs BMS in diabetic patients RestenosisTLRPatti G Am J Cardiol 2008;102:1328 –1334
33 DES vs BMS in diabetic patients DeathStentThrombosisMIPatti G Am J Cardiol 2008;102:1328 –1334
34 DES vs. BMS in Diabetic patients William B. Hillegass, MD, at al. Journal of the American College of Cardiology Vol. 60, No. 22, 2012
35 How to prevent cardiovascular events in diabetic patients? Better glycemic control?
36 Sospeso per mortalità elevata VADTACCORDSospeso per mortalità elevataADVANCETre studi molto recenti hanno dimostratoche l’ottimizzazione del controllo glicemico (HbA1C < 6,5%o < 7,0%) non ha portato a una riduzione significativa degli eventi cardiovascolari, anzi: in uno di essi e stato riportato un aumento della mortalita totale e cardiovascolare nel gruppo a controllo glicemico ottimizzato (3‑5). Tali risultati, tuttavia, sono almeno in parte riconducibili ai limiti intrinseci negli studi disponibili (inclusione di diabetici con lunga durata di malattia,alta percentuale di pazienti con neuropatia e altre complicanze croniche, eccessiva e rapida riduzione dell’HbA1c, aumento di frequenza dell’ipoglicemia, insufficiente durata del follow‑up).
38 Diabetes and ACS: “dangerous liasons” 65% of Diabetic Patients dies following cardiovascular events37% of ACS Patients is diabeticDiabetics with NSTEMI/UA, outcome is similar to non-diabetic patients with STEMIFuture risk cardiovascular events:Diabetic Patients = non-diabetic patients with previous MI
39 Conclusions Improve antithrombotic strategy 3939ConclusionsImprove antithrombotic strategyAcute and chronic tight glycemic controlOptimal revascularization strategyOptimal management of LV dysfunction39
40 The bitter fate of acute coronary syndrome in diabetics: diabetics have more adverse outcomes after PCISergio BertiFondazione CNR-Reg. Toscana G. MonasterioOspedale del Cuore, Massa
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