Has acute myocardial infarction mortality hit rock bottom Has acute myocardial infarction mortality hit rock bottom? Changes in patient characteristics, management, and 6-month outcomes over a period of 20 years in the FAST-MI programme 1995-2015 N. Danchin, E. Puymirat, F. Schiele, T. Simon, on behalf of the USIK, USIC 2000 and FAST-MI investigators

Consu lting/Royalties/Owner/ Stockholder of a healthcare company (Amgen AstraZeneca, Bayer, BMS, Boehringer -lngelheim Daiichi Sankyo, Eli-Lilly MSD Novo- ordisk, Pfizer, Sanofi) Research contracts (Amgen AstraZeneca, Bayer BMS, Boehringer -Ingelheim Daiichi Sankyo Eli-Lilly MSD Pfizer Sanofi)

Study sponsors USIK 1995: Roussel USIC 2000: Aventis – FAST-MI 2005: Pfizer, Servier FAST-MI 2010: AstraZeneca, Daiichi-Sankyo, Eli-Lilly, GSK, MSD, Novartis, Sanofi FAT-MI 2015: Amgen, AstraZeneca, Bayer, BMS, Boehringer -Ingelheim, Daiichi-Sankyo, Eli-Lilly, MSD, Pfizer, Sanofi

Background Early mortality in patients admitted for STEMI or NSTEMI has declined in the past 2 decades, and improved outcomes have been attributed to increased use of revascularisation but also to changes in patient characteristics and overall management. Few studies have compared trends in outcomes for STEMI and NSTEMI patients and little information beyond the early 2010s is available.

Aim To assess 6-month mortality in consecutive patients admitted to ICCUs for STEMI or NSTEMI and recruited in 5 one-month nationwide surveys in France, carried out 5 years apart since 1995

The French AMI registry programme 5 Nationwide French registries conducted 5 years apart since 1995, including consecutive adult patients with acute STEMI or NSTEMI, with symptom onset ≤ 48 hours, admitted alive to a coronary care unit (CCU) or an intensive care unit (ICU) within 48 hours of symptom onset, over a 1-month period (possible extension for up to one additional month). AMI criteria: 1) cardiac markers elevation with 2) compatible symptoms, or ST-T changes. No unstable angina. Exclusion of iatrogenic AMIs or MI diagnosis subsequently disproved. All type of institutions: academic teaching hospitals, community and regional hospitals, private clinics (for profit and not-for-profit), army hospitals. Compliance with GCP, patient consent and compliance with French law, including the law on data protection.

French AMI registries USIK 1995 USIC 2000 FAST-MI 2005 FAST-MI 2010 2152 patients 312 centres 1536 STEMI 616 NSTEMI 2320 patients 369 centres 1844 STEMI 476 NSTEMI 3059 patients 223 centres 3079 patients 213 centres 3813 patients 204 centres 1611 STEMI 1716 STEMI 1872 STEMI 1448 NSTEMI 1363 NSTEMI 1941 NSTEMI

STEMI patients: baseline characteristics USIK 1995a USIC 2000a FAST-MI 2005 FAST-MI 2010 FAST-MI 2015 P (n=1536) (n=1844) (n=1611) (n=1716) (n=1872) value Demography Age Female, n (%) 66.2±14.0 64.5±14.6 64.0±14.7 63.3±14.5 63.5±13.8 <0.001 431 (28) 499 (27) 458 (28) 423 (25) 469 (25) 0.04 Cardiovascular history and comorbidities, n (%) Myocardial Infarction Heart failure Peripheral artery disease 225 (15) 276 (15) 180 (11) 187 (11) 231 (12) 98 (6) 84 (5) 56 (3.5) 41 (2) 54 (3) 148 (10) 145 (8) 85 (5) 83 (5) 84 (4.5) % aged 60 years or less among STEMI patients 60 50 40 30 20 10 50.7 46.2 49 48.2 40.5 29.4 Men Women 23.4 25.5 17.5 13.7 1995 2000 2005 2010 2015

Patient behaviour: STEMI Time from symptom onset to first call 2000 2005 2010 2015 Median 120 90 74 25th; 75th percentiles 41; 360 30; 295 30; 240 30; 300 Direct call to EMS (SAMU) 60 50 40 30 20 10 48.8 50.9 41.3 23.2 2000 2005 2010 2015

Reperfusion treatment in STEMI 90 80 70 60 50 40 30 20 10 PPCI 76 % of STEMI patients 67 Thrombolysis No reperfusion 51 47 41 38 30 31 29 23 19 18 14 12 6 1995 PCI after lysis: 15% 2005 84% 2010 87% 2000 2015 60% 87%

STEMI: medications used in first 48 hours 100 80 60 40 Beta-blockers [VALU100 81 Statins 90 [VALU 100 80 60 40 20 ACE-i or ARBs 73 72 E] 78 E] [VALU E] 65 80 60 40 20 10 65 46 48 53 41 20 1995 2000 2005 2010 2015 Antiplatelet agents 1995 2000 2005 2010 2015 P2Y12 inhibitors 1995 2000 2005 2010 2015 Anticoagulants 97 100 92 95 96 100 80 60 40 20 100 80 60 40 20 88 85 Clopidogrel 100 80 60 40 20 96 UFH LMWH Prasugrel Ticagrelor 59 79 67 61 62 61 55 45 33 27 24 27 19 13.5 0 0 6.5 0 0 0 0 0 0 0 4 1995 2000 2005 2010 2015 2005 2010 2015 1995 2000 2005 2010 2015

NSTEMI patients: baseline characteristics USIK 1995a USIC 2000a FAST-MI 2005 FAST-MI 2010 FAST-MI 2015 P for Trend (n=616) (n=476) (n=1448) (n=1363) (n=1941) Demography Age (years) mean ± SD Female, n (%) 68.5±14.2 68.9±13.5 70.2±13.3 68.6±13.6 68.1±13.5 <0.001 188 (30.5) 130 (27) 510 (35) 406 (30) 581 (30) 0.75 Risk factors, n (%) Hypertension 303 (50) 272 (57) 962 (66) 847 (62) 1220 (63) Hypercholesterolemia 221 (37) 225 (48) 749 (52) 653 (48) 979 (54) Diabetes mellitus 122 (20) 123 (26) 422 (29) 370 (27) 522 (27) 0.001 Current smoking 157 (26) 103 (22) 322 (22) 334 (24.5) 566 (29) Obesity (BMI ≥30) 77 (13) 93 (22.5) 268 (21) 306 (24) 468 (25) Cardiovascular history and comorbidities, n (%) Myocardial Infarction 169 (27) 135 (28) 345 (24) 311 (23) 469 (24) 0.055 PCI - 77 (16) 260 (18) 314 (23) 462 (24) CABG 48 (10) 132 (9) 116 (8.5) 124 (6) 0.006 Heart failure 100 (16) 65 (14) 117 (8) 105 (8) 148 (8) PAD 73 (12) 70 (15) 197 (14) 161 (12) 190 (10) 0.003

Invasive strategies in NSTEMI 90 80 70 60 50 40 30 20 10 90 95 67 60 CAG 78 % of NSTEMI patients 71 PCI ≤ 72 hrs 65 55 PCI 51 44 39 25 9 12.5 1995 2000 2005 2010 2015

NSTEMI: medications used in first 48 hours 100 80 60 40 Beta-blockers 100 Statins 85 100 80 60 40 20 ACE-i or ARBs 77 71 78 64 66 80 60 40 20 10 71 60 61 57 51 43 42 37 20 1995 2000 2005 2010 2015 Antiplatelet agents 1995 2000 2005 2010 2015 P2Y12 inhibitors 1995 2000 2005 2010 2015 Anticoagulants 98 98 100 80 60 40 20 89 94 94 100 80 60 40 20 90 Clopidogrel 82 100 80 60 40 20 95 UFH LMWH Prasugrel Ticagrelor51.5 63 66 60 5550 41 48 41 38 34 13 17.5 5 0 0 0 0 0 0 0 0 0 1 1 1995 2000 2005 2010 2015 2005 2010 2015 1995 2000 2005 2010 2015

Six-month mortality Adjusted HR (95%CI) (reference 1995) 2000: 2005 2010 2015 STEMI NSTEMI 17.2 17.2 6.3 5.3 Adjusted HR (95%CI) (reference 1995) 2000: 0.76 (0.63-0.91) 0.92 (0.67-1.26) 2005: 0.56 (0.46-0.69) 0.66 (0.51-0.85) 2010: 0.45 (0.36-0.56) 0.40 (0.30-0.54) 2015: 0.32 (0.26-0.41) 0.40 (0.30-0.52) Figure 1

Crude and standardised 6-month mortality 20 16 12 8 4 A: STEMI Crude 17.2 15.4 12.711.8 9.7 9.1 6.9 6.8 5.3 5.3 2015 1995 2000 2005 2010 20 15 Crude B: NSTEMI 10 5 17.215.3 15.8 14.3 12.2 10.5 6.9 6.2 2010 6.3 6.3 2015 1995 2000 2005

STEMI patients: 6-month mortality by reperfusion therapy 30 23.4 25 16.9 16.4 15.1 20 15 10.8 8.9 7.4 6.7 10 5.0 4.8 5 1995 2000 2005 2010 2015 No reperfusion: Reperfusion: All STEMI Reference 1.00 1.00 Adjusted HR 0.70 (0.56-0.88) 0.85 (0.62-1.16) 0.76 (0.63-0.91) Adjusted HR 0.55 (0.42-0.72) 0.60 (0.44-0.84) 0.56 (0.46-0.69) Adjusted HR 0.60 (0.44-0.83) 0.41 (0.29-0.57) 0.45 (0.36-0.56) Adjusted HR 0.32 (0.21-0.49) 0.36 (0.26-0.50) 0.32 (0.26-0.41) No reperfusion Reperfusion Figure 2

NSTEMI patients: 6-month mortality by use of early PCI 30 25 No PCI ≤ 72h PCI ≤ 72h 20 15 [VALUE] [VALUE] 16.1 10 5 1995 2000 2005 3.2 2010 2015 No PCI ≤72 hours: Reference 1.00 Adjusted HR 1.01 (0.73-1.39) Adjusted HR 0.74 (0.56-0.97) Adjusted HR 0.53 (0.38-0.73) Adjusted HR 0.50 (0.36-0.68) PCI ≤72 hours: 1.00 0.28 (0.10-0.76) 0.19 (0.08-0.41) 0.09 (0.04-0.21) 0.11 (0.05-0.23) All NSTEMI: 0.92 (0.67-1.26) 0.66 (0.51-0.85) 0.40 (0.30-0.54) 0.40 (0.30-0.52) Figure 2

Final thoughts From 1995 to 2015, 6-month mortality of both STEMI and NSTEMI patients has considerably decreased, together with major increases in use of procedures over time. Use of recommended secondary prevention medications has also increased until 2010 but levels down since then. In STEMI patients, mortality has continued to decrease after 2010, to reach an all-time low in 2015. In NSTEMI patients, despite recent changes in antithrombotic medications at the acute stage, mortality has remained similar in 2015, compared with 2010. Prolonged follow-up will determine whether improvement in survival will persist or materialise in both types of patients.

Acknowledgements FAST-MI is a registry of the French Society of Cardiology Supported by: Funding of FAST-MI 2015: Amgen, AstraZeneca, Bayer, BMS/Pfizer, Boehringer-Ingelheim, Daïchi-Sankyo/Eli-Lilly, MSD, Sanofi We are indebted to: The patients who accepted to participate in the surveys All clinicians involved in the studies All the devoted personnel involved at the Société Française de Cardiologie, and URCEST, AP-HP, Hôpital St Antoine .

Circulation. 2017;136:00–00. DOI: 10.1161/CIRCULATIONAHA.117. 030798

Barcelona Aug, 26 2017