Italian Elderly Il trattamento della Sindrome Coronarica Acuta nel paziente anziano ACS Network Stefano Savonitto Ospedale Manzoni Lecco
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
Age class distribution in ACS ANMCO registries, y 2001-2014 N= 13,235 N= 15,039 De Luca L. Openheart 2014, epub December 17 De Luca L. J Am Heart Ass 2016;5:e004202
years Ospedale Manzoni - Lecco Comparing mean ages of Italian ACS registries and guideline-building trials NSTEACS STEMI women 80-75- 70- men women 65-74 men 60-55- 68 62 62 62 68 63 60 59 59 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
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 + 2008-2011 2012-2017 2014-2016 Italian Elderly ACS study (trial + registry) NCT00510185 Elderly ACS 2 trial NCT01777503 LADIES ACS study NCT01997307 Time trends across ANMCO registries 2001-2014
Italian Elderly ACS Network Distribution of study Centers
Gender by Age class distribution in STEMI ANMCO registries, y 2001-2014 100%- 80%- men women 60%- 40%- 20%- 0-87 13 <55 N= 2,896 83 17 >55-64 N= 3,192 72 28 >65-74 N= 3,414 52 48 >75 N= 3,733 De Luca L. J Am Heart Ass 2016;5:e004202
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= 0.010 P= 0.076 women P= 0.382 P= 0.097 55-64 65-74 75-84 >85 years Age class Savonitto S. Am J Med 2016;129:1205-12
Metanalysis of PPCI vs lysis in elderly patients with STEMI Bueno H. Eur Heart J 2011;32:51
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
In-H mortality adjusted De Luca L. J Am Heart Ass 2016;5:e004202
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
percent Ospedale Manzoni - Lecco Overall incidence of Cardiogenic Shock in ACS by age Italian ANMCO CCU registries y 2000-2014 (n=28,217) 10-9- 8-7- 6-5- 4-3- 2-1- 0- P<.0001 2.88 7.04 overall N=28,217 P<.0001 3.94 STEMI N=13,201 10.9 De Luca L. Eur J Heart Fail 2015;17:1124 <75y (18,700) >75y (9,517) P<.0001 4.59 1.80 NSTEACS N=15,015
percent Ospedale Manzoni - Lecco Overall incidence of CS in ACS by sex Italian ANMCO CCU registries y 2000-2014 (n=28217) 9-8- 7-6- 5-4- 3-2- P<.0001 3.69 5.65 P<.0001 4.81 8.67 2.65 Men (19,685) Women (8,532) P=.01 3.36 1-0- overall N=28,217 STEMI N=13,201 NSTEACS N=15,015 De Luca L. Eur J Heart Fail 2015;17:1124
Age- and sex-matched evolution of STEMI treatment in Italy In-hospital events 2001 2006 2008 2009 2014 P for trend (n=1787) (n=2935) (n=7214) (n=3625) (n=1365) Re-MI Men (9544) 3.12 1.84 1.02 1.67 0.65 0.0002 Women (3691) 3.39 0.76 1.28 1.69 0.67 0.0679 Stroke Men 1.35 0.74 0.59 0.72 0.65 0.1208 Women 1.69 1.68 1.09 0.91 1.00 0.1392 Shock Men 6.14 3.69 5.42 3.40 5.58 0.1643 Women 12.11 8.87 9.05 6.78 6.02 0.0011 Maj Bleed Men 1.66 0.68 0.98 0.77 0.78 0.1129 Women 4.36 2.45 2.44 3.13 2.68 0.4176 De Luca L. J Am Heart Ass 2016;5:e004202
Percent Ospedale Manzoni - Lecco 100-90- 80-70- 60-50- 40-30- 20-10- 0-35 2001 2006-7 2010 Revascularization (PCI/CABG) 12 BLITZ 72 73 46 In-ACS outcome 48 MANTRA De Luca L. Eur J Heart Fail 2015;17:1124 <75 (n=288) 67 2014 P trend=0.0014 >75 (n=377) P trend<0.0001 60 EYESHOT
percent Ospedale Manzoni - Lecco In hospital mortality of CS in STEMI by age ANMCO registries 2001-2014 100-90- 80-70- 60-50- 40-30- 20-10- 0-52 2001 2006-7 2009 2010 83 BLITZ 34 In-ACS outcome <75y (n=373) >75y (n=404) 63 58 23 BLITZ 4 33 49 MANTRA 2014 P trend=0.03 P trend<0.0001 52 33 EYESHOT De Luca L. Eur J Heart Fail 2015;17:1124
percent Ospedale Manzoni - Lecco In hospital mortality of CS in STEMI by gender ANMCO registries 2001-2014 100-90- 80-70- 60-50- 40-30- 20-10- 0-73 2001 2006-7 2009 2010 68 BLITZ Men (n=458) 44 In-ACS outcome Women (n=319) 55 51 33 38 BLITZ 4 46 MANTRA 2014 P trend=0.0001 P trend=0.03 50 38 EYESHOT De Luca L. Eur J Heart Fail 2015;17:1124
30% Thiele H. N Engl J Med 2017;377:2419-32
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
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 > 65 74 yrs Men Women > 75 yrs Men Women (n=2020) (n=787) (n=1163) (n=658) (n=533) (n=306) 1.04 (0.81-1.33) 0.78 1.34 (0.88-2.06) 0.17 0.60 (0.47-0.79) <.01 1.10 (0.74-1.62) 0.66 0.63 (0.46-0.86).004 0.87 (0.57-1.33) 0.52 0 0.5 1 2.0 Invasive Better Conservative Better Damman P et al. Heart 2012;98:207-13
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;5:906-16 Tegn A. Lancet 2016;387:1057-65 Morici N. J Am Geriatr Soc 2016, epub Oct 5
De Luca L. Openheart 2014, epub December 17
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) 12-15- 12- P for trend <0.0001 P for trend <0.0001 15-9- 9-6- 3-0- 6.1 (4.9) 4.3 (3.4) Blitz 2001 Blitz-2 2003 3.6 (4.9) 2.2 (2.8) IN-ACS 2007 Blitz-4 2009-10 2.8 (3.4) MANTRA 2009-10 6-3- 0-12.1 (7.2) 10.8 (9.3) 9.0 (6.1) Blitz 2001 Blitz-2 2003 IN-ACS 2007 8.8 (5.6) Blitz-4 2009-10 9.3 (7.1) MANTRA 2009-10 De Luca L. Openheart 2014, epub December 17
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, 2001 28 / 192 14.6 (9.9-20.4) 8.9 (5.2-13.8) reference BLITZ-2, 2003 26 / 347 7.5 (5.0-10.8) 7.8 (5.2-11.1) 0.52 (0.28-0.96) 0.04 IN-ACS, 2006-7 65 / 923 7.0 (5.5-8.9) 8.8 (7.0-10.8) 0.43 (0.26-0.72) 0.001 BLITZ-4, 2009-10 121 / 1941 6.2 (5.2-7.4) 9.7 (8.4-11.1) 0.34 (0.21-0.56) <0.0001 MANTRA, 2009-10 90 / 947 9.5 (7.7-11.6) 9.5 (7.7-11.6) 0.55 (0.33-0.92) 0.02 0 0.2 0.4 0.6 0.8 1 1.2 1.4 De Luca L. Openheart 2014, epub December 17
Death, MI, stroke and rehospitalization for CV reasons or bleeding @ 1 year De Carlo M. JACC Intv 2015;8:791
Radial vs femoral approach to PCI in RIVAL Rates of ACUITY major bleeding by age Cantor WJ. AHJ 2015;170:880
Radial approach to PCI in Recent RCT of elderly ACS patients 90% 80% 78% 100-80- 60-40- 20-0- ANTARCTIC Elderly ACS 2 Lancet 2016 Lancet 2016 Circulation 2018
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
5-25- 20-15- 10-2.5-0- RCT+ Registry All options 3.5 15.0 It. Elderly ACS 1-year mortality in Elderly ACS trials (Age 75 years) RCT All options 2.1 10.3 PLATO RCT No revasc 1.5 9.0 TRILOGY RCT PCI only 3.0 2.0 ANTARCTIC Non Cv DEATH Cv DEATH RCT PCI only 2.2 4.0 Elderly ACS 2 JACC Intv 2012 Circulation 2012 Circulation 2013 Lancet 2016 Circulation 2018
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;353:2373-83.
Bleeding complications in CHARISMA Becker RC. Circulation 2010;121:2575
Newer antiplatelet treatments compared to clopidogrel in ACS: Patients >75 y.o. 25-20- PLATO (n=2878) Adj HR 0.89 (IC 0.74-1.08) clopid ticag 25-20- TRITON (n=1809) HR 0.94 (CI 0.75-1.18) clopid prasug 15-15- 10-5- 0-18.3 17.2 Adj HR 1.18 (IC 0.73-1.59) 7.1 8.3 10-5- 0-18.3 17.2 HR 1.36 (CI 0.81-2.27) 3.4 4.2 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
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;388:2015-22
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