POSTER 3 7:24 – 7:31 Impact of an Invasive Strategy on In-Hospital Outcomes in Nonagenarians with Acute Coronary Syndrome: Insights from the AMI-OPTIMA Study  Presenter: Etienne L. Couture Authors: Etienne L. Couture M, Paul Farand MD MSc, Michel Nguyen MD, Catherine Allard MSC, Jonathan Afilalo MD MSC, Marc Afilalo MD, Erick Schampaert MD Mark Eisenberg MD MPH, Martine Montigny MD MSC, Samer Mansour MD, Simon Kouz MD MSC, Jean- Claude Tardif MD, Thao Huynh MD, MSC, PHD

The Impact of an Invasive Strategy on In-Hospital Outcomes in Nonagenarians with Acute Coronary Syndrome: Insights from the AMI-OPTIMA Study. Fellows Poster Competition Montreal Live Symposium 2016 Etienne Couture, Paul Farand, Michel Nguyen, Catherine Allard, Jonathan Afilalo, Marc Afilalo, Erick Schampaert, Mark Eisenberg, Martine Montigny, Samer Mansour, Simon Kouz, Jean-Claude Tardif, Claude Lauzon, Thao Huynh Thanh.

Research Question Does the invasive strategy is worthwhile in nonagenarians ACS patients in regards to the risks and benefits ?

Introduction ACC/AHA Guidelines (Acute coronary care in the elderly) - ‘’…Very elderly have reasonable outcomes following revascularization in ACS” Meta-Analysis FRISC II / ICTUS / RITA-3 (routine vs selective invasive) - 5-years composite in > 75 yo : HR 0.71, 95% CI 0.55 to 0.91 After Eighty-Study (Lancet 2016) - RCT 457 > 80 yo NSTEACS patients; invasive vs conservative; mean fu 1.5 y - Primary composite endpoint HR 0.52 (p<0.001) - Mortality HR 0.89 (p<0.53) - Nonagenarians (N = 34) HR 1.21 (p=0.64) Alexander KP Circulation 2007; 115: 2549–69. Tegn N et al. Lancet 2016; 387: 1057–65 Damman P et al. Heart 2012; 98: 207–13.

Methods AMI-OPTIMA Study Ethical Approval Statistical Analysis - Cluster Randomized study: 100 consecutive ACS in 24 hospitals in Québec (2009 & 12) - Initial aim: knowledge translation on optimal discharge medication Ethical Approval - McGill Universitary Center (coordinating hospital) Statistical Analysis - Four age groups stratification (<70, 70-79, 80-89, >=90) - Multivariate logistic regression to identify predictors of invasive strategy - Inverse probability weighted analysis

Baseline Characteristics and Clinical Presentation   Age, years Number of patients Proportion of total AMI-OPTIMA patients <70 N=2,394 52% 70-79 N=1,031 23% 80-89 N=941 21% 90 N=202 4.4% P Value For Trend Baseline Characteristics Median Age, years (Q1:Q3) 58 (62-64) 75 (72-77) 84 (82-87) 93 (91-95) <0.001 Female, % 576 (24) 377 (37) 454 (48) 145 (72) Hypertension, % 1250 (52) 749 (73) 738 (78) 157 (78) Diabetes Mellitus, % 590 (25) 357 (35) 312 (33) 45 (22) Dyslipidemia, % 1291 (54) 644 (63) 536 (57) 74 (37) 0.45 Current Smoker, % 983 (41) 157 (15) 47 (5.0) 1 (0.5) Obesity (BMI>30), % 686 (29) 193 (19) 109 (12) 9 (4.5) Peripheral Vascular Artery Disease, % 150 (6.3) 137 (13) 106 (11) 15 (7.4) Chronic Kidney Disease, % 170 (7.1) 217 (21) 285 (30) 64 (32) Prior PCI, % 502 (21) 263 (26) 200 (21) 19 (9.4) 0.14 Prior CABG, % 121 (5.1) 117 (11) 124 (13) 14 (6.9) Clinical Presentation STEMI, % 849 (36) 234 (23) 161 (17) 38 (19) NSTEMI, % 859 (36) 455 (44) 492 (52) 114 (56) Unstable Angina, % 501 (21) 235 (23) 11 (5.4) Non-specified ACS, % 123 (5.1) 77 (7.5) 85 (9.0) 34 (17)

In-hospital medical and invasive therapies Age, years   <70 N=2,394 70-79 N=1,031 80-89 N=941 90 N=202 P Value For Trend  Medications Fibrinolysis, % 74 (3.1) 15 (1.5) 9 (1.0) 0 (0) <0.001 DAPT, % 2,040 (85) 770 (75) 621 (66) 89 (44) Intravenous unfractionated heparin, % 1,995 (83) 804 (78) 608 (65) 109 (54) LMWH, % 711 (30) 332 (32) 328 (35) 68 (34) 0.004 Fondaparinux, % 15 (0.6) 11 (1.1) 14 (1.5) 0.160 Bivalirudin, % 174 (7.3) 58 (5.6) 43 (4.6) Gp2b3a inhibitors, % 620 (26) 169 (16) 47 (5) Invasive Procedures Cardiac catheterization, % 2,210 (92) 856 (83) 505 (54) 40 (20) PCI, % of patients who underwent angiogram Stent, % of patients who underwent PCI 1674 (76) 538 (62) 353 (70) 29 (73) Bare metal stent, % 972 (58) 293 (54) 226 (64) 22 (76) Drug-eluting stent, % 545 (33) 191 (36) 92 (26) 4 (14) 0.07 Both types of stents, % 65 (3.9) 13 (2.4) 6 (1.7) 1 (3.4) 0.03 No stent, % 26 (1.6) 9 (1.7) 5 (1.4) 0 (0) 0.81 Staged PCI, % 147 (6.1) 55 (5.3) 40 (4.2) 1 (0.5) IABP, % 106 (4.4) 50 (4.8) 23 (2.4) 3 (1.5) In-Hospital CABG, % 223 (9.3) 144 (14) 52 (5.5)

In-Hospital Outcomes Stratified by Age Age, years <70 (n=2,394) 70-79 (n=1,031) 80-89 (n=941) 90 (n=202) P Value For Trend All-cause mortality, % 31 (1.3) 36 (3.5) 95 (10) 48 (24) <0.001 Cardiovascular mortality, % 26 (1.1) 24 (2.3) 78 (8.3) 39 (19) Stroke, % 6 (0.3%) 3 (0.3%) 13 (1.4%) 4 (2.0%) Cardiogenic shock, % 53 (2.2) 28 (2.7) 31 (3.3) 8 (4.0) 0.03 Mechanical ventilation, % 80 (3.3) 44 (4.3) 47 (5.0) 10 (5.0) 0.02 Heart failure, % 133 (5.6) 104 (10) 140 (15) 42 (21) Ventricular arrhythmia, % 125 (5.2) 41 (4.0) 30 (3.2) 0.01 Brady-arrhythmia, % 38 (1.6) 31 (1.0) 27 (2.9) 6 (3.0) Acute Kidney Injury 172 (7.2) 172 (17) 244 (26) 65 (32) Nosocomial infection 30 (1.3) 18 (1.7) 20 (2.1) 0.001 Length of hospitalization,days 5 (3-7) 6 (4-11) 8 (5-14) 8 (5-15) More than 5 days 898 (38) 556 (55) 622 (67) 148 (74)

Independent Predictors of All-Cause Mortality and Invasive Strategy   OR for all-cause mortality (95% CI) P values for all-cause mortality OR for invasive strategy for invasive strategy Age (continuous) 1.05 (1.02-1.08) 0.002 0.92 (0.91-0.92) <0.001 Female 2.95 (1.56-5.55) 0.001 0.62 (0.50-0.78) MVD 2.13 (1.02-4.46) 0.05 NA In-hospital PCI 0.28 (0.14-0.56) In-hospital CABG 0.21 (0.07-0.67) 0.009 Cardiogenicshock 11.65 (5.20-26.09) Mechanical ventilation 6.61 (2.08-21.05) Acute kidney injury 5.52 (2.93-10.41) Ventricular arrhythmia Diabetes mellitus Prior CABG Chronic kidney disease Admission Hb <100 gm/L STEMI 1.24 (2.95-7.00)  NA 0.01 0.74 (0.58-0.93) 0.61 (0.44-0.85) 0.33 (0.25-0.43) 0.53 (0.37-0.77)  2.14 (1.59-2.88) 0.004  <0.001

In-Hospital Outcomes stratified by invasive vs conservative strategy   Unadjusted Rate Inverse Probability Weighted In-Hospital Outcome Age, yrs Conservative (%) Invasive P Value Odds Ratio of invasive strategy compared to conservative strategy 95% CI All-cause mortality, (%) <70 70-79 80-89 90 7 (3.8) 13 (7.4) 67 (15) 41 (25) 24 (1.1) 23 (2.7) 28 (5.5) 7 (18) 0.002 <0.001 0.30 3.7 9.0 15.3 25.7 1.1 2.9 6.2 17.3 0.30 (0.19-0.46) 0.30 (0.20-0.46) 0.37 (0.27-0.50) 0.60 (0.37-0.98) 0.036 CV death, (%) 6 (3.3) 8 (4.6) 53 (12.1) 34 (21.0) 20 (0.9) 16 (1.9) 25 (5.0) 5 (13.0) 0.003 0.03 0.22 3.3 12.1 21.3 0.9 2.0 5.7 12.7 0.28 (0.17-0.44) 0.32 (0.19-0.52) 0.44 (0.31-0.61) 0.54 (0.31-0.92) 0.021 Stroke 0 (0.0) 2 (1.1) 6 (1.4) 3 (1.9) 6 (0.3) 1 (0.1) 7 (1.4) 1 (2.5) 0.48 0.02 0.99 0.79 0.0 1.5 1.6 0.6 0.1 1.4 2.5 -NA 0.07 (0.01-0.49) 0.87 (0.41-1.83) 1.72 (0.41-7.29) - 0.85 0.50 TIMI major 6 (3.4) 13 (3.0) 68 (3.1) 41 (4.8) 3 (7.5) 0.89 0.43 0.12 0.06 3.6 4.5 2.7 3.1 4.8 4.4 9.6 0.87 (0.63-1.19) 1.07 (0.71-1.62) 1.65 (1.00-2.71) 5.26 (1.75-15.74) 0.37 0.73 0.05 0.001 TIMI minor 16 (3.7) 7 (4.3) 80 (3.6) 35 (4.1) 24 (4.8%) 0.80 0.68 0.41 0.40 4.0 4.1 4.2 7.1 0.89 (0.66-1.20) 1.55 (0.95-2.54) 1.45 (0.89-2.37) 1.85 (0.76-4.50) 0.45 0.09 0.14 0.19

In-Hospital Outcomes stratified by invasive vs conservative strategy

In-Hospital Outcomes stratified by invasive vs conservative strategy

Limitations Retrospective design Unmeasured confunding variables (frailty, cognitive impairment, physiological age) 202 Nonagenarians: but still the largest study to date

Conclusion Nonagenarians ACS patients: Disctinct population (survival biais) Very high in-hospital mortality (24%) Less likely to undergo invasive strategy (20%) After inverse probability weighted analysis: Invasive strategy is associated with a lower All-cause/CV death The absolute benefit of invasive strategy increase with age Invasive strategy is associated with higher rate of major bleeding in patients >80 yo. Despiste this, there is still a mortality benefit.

Thank You

Inverse Probability Weighted Deb et al. Canadian Journal of Cardiology 32 (2016) 259e265