Il trattamento della Sindrome Coronarica Acuta nel paziente anziano

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1 Italian Elderly Il trattamento della Sindrome Coronarica Acuta nel paziente anziano ACS Network Stefano Savonitto Ospedale Manzoni Lecco

2 DISCLOSURE INFORMATION Stefano Savonitto negli ultimi due anni ho avuto i seguenti rapporti, anche di finanziamento, con soggetti portatori di interessi commerciali in campo sanitario: Astra-Zeneca, Bayer, Bristol Myers Squibb Daiici Sankio, Novartis, Pfizer

3 Age class distribution in ACS ANMCO registries, y N= 13,235 N= 15,039 De Luca L. Openheart 2014, epub December 17 De Luca L. J Am Heart Ass 2016;5:e004202

4 years Ospedale Manzoni - Lecco Comparing mean ages of Italian ACS registries and guideline-building trials NSTEACS STEMI women men women men BLITZ 4 Eur Heart J Acute CV Care 2012 TIMI 18 NEJM 2001 RITA III Lancet 2002 ICTUS NEJM 2005 BLITZ 4 Eur Heart J Acute CV Care 2012 HORIZONS NEJM 2008 TRITON Lancet 2009 PLATO Circulation 2011 Savonitto S. Rev Esp Cardiol 2014;67:564

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6 Our response to the call Italian ACS Elderly Network Prospective studies >2800 patients 63 Centers Prospective registries 14 years, >200 centers/registry >28,000 patients Italian Elderly ACS study (trial + registry) NCT Elderly ACS 2 trial NCT LADIES ACS study NCT Time trends across ANMCO registries

7 Italian Elderly ACS Network Distribution of study Centers

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9 Gender by Age class distribution in STEMI ANMCO registries, y %- 80%- men women 60%- 40%- 20% <55 N= 2, >55-64 N= 3, >65-74 N= 3, >75 N= 3,733 De Luca L. J Am Heart Ass 2016;5:e004202

10 Extent of CAD in men and women according to age class: the LADIES ACS study Male Gensini score 59.6 ±35.9 Female Gensini score 49.7 ±31.7 P<0.001 men P= P= women P= P= >85 years Age class Savonitto S. Am J Med 2016;129:

11 Metanalysis of PPCI vs lysis in elderly patients with STEMI Bueno H. Eur Heart J 2011;32:51

12 Men (n=9544) Primary PCI Primary PCI In-H mortality In-hospital mortality Women (n=3691) De Luca L. J Am Heart Ass 2016;5:e004202

13 In-H mortality adjusted De Luca L. J Am Heart Ass 2016;5:e004202

14 Possible reasons for a persistently higher adjusted mortality in women after the shift from thrombolysis to primary PCI Less reperfusion therapy More bleeding More, and more fatal, cardiogenic shock De Luca L. J Am Heart Ass 2016;5:e004202

15 percent Ospedale Manzoni - Lecco Overall incidence of Cardiogenic Shock in ACS by age Italian ANMCO CCU registries y (n=28,217) P< overall N=28,217 P< STEMI N=13, De Luca L. Eur J Heart Fail 2015;17:1124 <75y (18,700) >75y (9,517) P< NSTEACS N=15,015

16 percent Ospedale Manzoni - Lecco Overall incidence of CS in ACS by sex Italian ANMCO CCU registries y (n=28217) P< P< Men (19,685) Women (8,532) P= overall N=28,217 STEMI N=13,201 NSTEACS N=15,015 De Luca L. Eur J Heart Fail 2015;17:1124

17 Age- and sex-matched evolution of STEMI treatment in Italy In-hospital events P for trend (n=1787) (n=2935) (n=7214) (n=3625) (n=1365) Re-MI Men (9544) Women (3691) Stroke Men Women Shock Men Women Maj Bleed Men Women De Luca L. J Am Heart Ass 2016;5:e004202

18 Percent Ospedale Manzoni - Lecco Revascularization (PCI/CABG) 12 BLITZ In-ACS outcome 48 MANTRA De Luca L. Eur J Heart Fail 2015;17:1124 <75 (n=288) P trend= >75 (n=377) P trend< EYESHOT

19 percent Ospedale Manzoni - Lecco In hospital mortality of CS in STEMI by age ANMCO registries BLITZ 34 In-ACS outcome <75y (n=373) >75y (n=404) BLITZ MANTRA 2014 P trend=0.03 P trend< EYESHOT De Luca L. Eur J Heart Fail 2015;17:1124

20 percent Ospedale Manzoni - Lecco In hospital mortality of CS in STEMI by gender ANMCO registries BLITZ Men (n=458) 44 In-ACS outcome Women (n=319) BLITZ 4 46 MANTRA 2014 P trend= P trend= EYESHOT De Luca L. Eur J Heart Fail 2015;17:1124

21 30% Thiele H. N Engl J Med 2017;377:

22 5-year death/mi in the FIR collaboration SI= selective invasive RI= routine invasive >75y 65-74y <65y Damman P et al. Heart 2012;98:207-13

23 5-year death/mi in the FIR collaboration Invasive vs conservative approach in NSTEACS Age group n of Pts HR (95% CI) p <65 yrs Men Women > yrs Men Women > 75 yrs Men Women (n=2020) (n=787) (n=1163) (n=658) (n=533) (n=306) 1.04 ( ) ( ) ( ) < ( ) ( ) ( ) Invasive Better Conservative Better Damman P et al. Heart 2012;98:207-13

24 Early aggressive vs initially conservative In elderly patients with NSTEACS and elevated Tn Italian ACS Elderly Study Italian Elderly ACS Tn+ patients Mean age 82 years After eighty NSTEACS 95% Tn+ Mean age 85 years Death, MI, Stroke, Rehosp Early Aggressive Early Aggressive Initially Conserv Initially Conserv Savonitto S. JACC Intv 2012;5: Tegn A. Lancet 2016;387: Morici N. J Am Geriatr Soc 2016, epub Oct 5

25 De Luca L. Openheart 2014, epub December 17

26 Mean delay between admission and coronary angiography and mean length of hospital stay in NSTEMI Patients >75 y across ANMCO registries from 2001 to 2010 Mean delay between admission and angiography (days) Mean length of hospital stay (days) P for trend < P for trend < (4.9) 4.3 (3.4) Blitz 2001 Blitz (4.9) 2.2 (2.8) IN-ACS 2007 Blitz (3.4) MANTRA (7.2) 10.8 (9.3) 9.0 (6.1) Blitz 2001 Blitz IN-ACS (5.6) Blitz (7.1) MANTRA De Luca L. Openheart 2014, epub December 17

27 Standardized all-cause mortality at 30 days in elderly patients with NSTEMI adjusted for gender, age, SBP, HR, diabetes, Hx of HF, prior stroke/tia, POAD, CKD, Killip, AF, study Study, year N. events/pts 30-day 30-day multivariable observed death standardised death logistic regression analysis % (95% CI) % (95% CI) OR and 95% CI p value BLITZ, / ( ) 8.9 ( ) reference BLITZ-2, / ( ) 7.8 ( ) 0.52 ( ) 0.04 IN-ACS, / ( ) 8.8 ( ) 0.43 ( ) BLITZ-4, / ( ) 9.7 ( ) 0.34 ( ) < MANTRA, / ( ) 9.5 ( ) 0.55 ( ) De Luca L. Openheart 2014, epub December 17

28 Death, MI, stroke and rehospitalization for CV reasons or 1 year De Carlo M. JACC Intv 2015;8:791

29 Radial vs femoral approach to PCI in RIVAL Rates of ACUITY major bleeding by age Cantor WJ. AHJ 2015;170:880

30 Radial approach to PCI in Recent RCT of elderly ACS patients 90% 80% 78% ANTARCTIC Elderly ACS 2 Lancet 2016 Lancet 2016 Circulation 2018

31 Cumulative risk estimate of death up to 405 days of follow up Italian ACS Elderly Study NCV death 20% CV death 80% Morici N. Am J Cardiol 2013;112:1

32 RCT+ Registry All options It. Elderly ACS 1-year mortality in Elderly ACS trials (Age 75 years) RCT All options PLATO RCT No revasc TRILOGY RCT PCI only ANTARCTIC Non Cv DEATH Cv DEATH RCT PCI only Elderly ACS 2 JACC Intv 2012 Circulation 2012 Circulation 2013 Lancet 2016 Circulation 2018

33 Excess of upper GI complications with low-dose aspirin Depending on previous clinical history Patrono C. NEJM 2005 Patrono C. N Engl J Med 2005;353:

34 Bleeding complications in CHARISMA Becker RC. Circulation 2010;121:2575

35 Newer antiplatelet treatments compared to clopidogrel in ACS: Patients >75 y.o PLATO (n=2878) Adj HR 0.89 (IC ) clopid ticag TRITON (n=1809) HR 0.94 (CI ) clopid prasug Adj HR 1.18 (IC ) HR 1.36 (CI ) D+MI+stroke PLATO non-cabg major bleeding D+MI+stroke TIMI non-cabg major bleeding Husted S. Circ CV Qual Outcomes 2012;5:680 Wiviott S. N Engl J Med 2007;357:2001

36 877 ACS pts >75 y undergoing PCI and randomised to aspirin and either prasugrel 5 mg or PFT-adjusted P2Y 12 Primary Endpoint CV death, MI, stroke, stent thrombosis, urgent revascularization or BARC 2, 3 or 5 Cayla G. Lancet 2016;388:

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38 Tailored strategy in elderly NSTEACS patients Italian ACS-2 Elderly Study 1. Typical troponin elevation is crucial 2. Typical ECG changes are also crucial 3. Check anemia with fast algorithm 4. Check egfr by CG and learn how to treat pts with CKD 5. Diabetes in the elderly is a marker: don t treat glyc aggressively 6. Keep anticoagulation low 7. Keep GPI moderate 8. Always go radial 9. Invasive, culprit vessel only, treatment of cardiogenic shock 10.Be prudent with long-term antiplatelet therapy Savonitto S. Rev Esp Cardiol 2014;67:564