TIDES-ACS trial. Comparison of TItanium-nitride-oxide coated bioactive stent to the Drug (everolimus)-eluting Stent in Acute Coronary Syndrome

Transcription

1 TIDES-ACS trial Comparison of TItanium-nitride-oxide coated bioactive stent to the Drug (everolimus)-eluting Stent in Acute Coronary Syndrome Pasi P Karjalainen

2 Potential conflicts of interest Speaker's name: Pasi P Karjalainen I have the following potential conflicts of interest to report: Receipt of grants / research supports: Abbott Receipt of honoraria or consultation fees: AstraZeneca Biotronik Boston Scientific Medtronic St. Jude Medical

3 TIDES-ACS Patients presenting with Acute Coronary Syndrome BAS Titanium-Nitride-Oxide-coated Bioactive Stent 989 Patients 12 International Sites Randomisation 2:1 EES Everolimus-Eluting Stent with biodegradable polymer 502 Patients Clinical Follow-up 30d 6mo 12mo 18mo 2yr 3yr 4yr Clinical Primary endpoint 5yr Primary Endpoint: MACE (Cardiac death, MI, and TLR) at 12 months Co-Primary Endpoint: Cardiac death, MI, major bleeding at 18 months PI P Karjalainen (FIN) Co-PI K Kervinen (FIN), J van Der Heyden (NED), H Romppanen (FIN), P Tonino (NED) CEC: J Marco (FRA), A de Belder (UK), R Wiseth (NOR), J Gomez-Hospital (SPA), D Formigli (ITA) ClinicalTrials.gov: NCT Minerva Cardioangiol. 2015;63:21-9.

4 TIDES-ACS Background ESC 2017 congress, Late Breaking clinical trials-session Co-Primary Non-Inferiority Endpoint Met

5 TIDES-ACS Devices Cobalt-chromium-based BAS (OPTIMAX ) Platinum-chromium-based biodegradable-polymer EES (SYNERGY ) Stent Platform Cobalt-chromium platform Helicoidal Design Strut thickness 75 µm Platinum-chromium platform Slotted Tube Strut thickness (74-81) µm Drug --- Everolimus Drug Density µg/cm 2 Coating Titanium-Nitride-Oxide --- Polymer --- Abluminal poly (D,L-lactide-coglycolide) (4 µm) Manufacturer Hexacath, Paris, France Boston Scientific Corp. MA. USA

6 TIDES-ACS Clinical Sites Investigators Hospital n J Lalmand C.H.U. de Charleroi, Charleroi, Belgium 50 P Tonino Heartcenter Catharina Hospital, Eindhoven, Netherlands 391 M Laine, M Pentikäinen Helsinki University Hospital, Helsinki, Finland 27 J Sia, T Pinola Kokkola Central Hospital, Kokkola, Finland 82 H Romppanen, A Perälä Kuopio University Hospital, Kuopio, Finland 220 P Frambach INCCI Luxembourg Hospital, Luxembourg 86 J van der Heyden St Antonius Hospital, Nieuwegein, Netherlands 236 K Kervinen, M Niemelä Oulu University Hospital, Oulu, Finland 128 P Karjalainen, W Nammas, J Mikkelsson Satakunta Central Hospital, Pori, Finland 174 A Serra Hospital Sant Pau, Barcelona, Spain 30 Dr. Vaquerino, M Fuertes Hospital del Mar, Barcelona, Spain 17 M Pietilä, J Airaksinen Turku University Hospital,Turku, Finland 50

7 TIDES-ACS Baseline Characteristics BAS (n=989) EES (n=502) P value Age (years) 62.7 ± ± Male 75.3% 76.3% 0.70 Diabetes 14.2% 12.5% Insulin treated 2.3% 3.8% 0.14 Hyperlipidemia 41.5% 40.2% 0.66 Hypertension 46.8% 43.6% 0.25 Current smoker 31.2% 35.9% 0.08 Prior myocardial infarction 7.6% 9.0% 0.37 Prior PCI 7.0% 6.6% 0.83 Prior CABG 0.6% 1.2% 0.23 NSTEMI 46.3% 45.0% 0.66 STEMI 44.9% 47.6% 0.32

8 TIDES-ACS Lesion Characteristics BAS (n=989) EES (n=502) P value No. of lesions treated/patient 1.17 ± ± or 3 vessels treated 36.0% 36.7% 0.75 RVD a (mm) 3.20 ± ± Lesion length (mm) 14.9 ± ± Culprit lesion location - Left anterior descendens 45.7% 45.8% Left circumflex 21.2% 20.0% Right coronary artery 33.0% 34.1% 0.56 B2/C type complex lesion 22.5% 21.7% 0.67 Thrombus in culprit lesion 33.1% 36.7% 0.18 a Reference vessel diameter

9 TIDES-ACS Procedural Data BAS (n=989) EES (n=502) P value Radial access 75.8% 76.9% 0.65 No. of stents/culprit lesion 1.13 ± ± Stent diameter (mm) 3.22 ± ± Stent length (mm) 18.6 ± ± Total stent length/lesion (mm) 20.5 ± ± Post-Dilatation 33.0% 38.0% 0.06 Stent failure 0.3% 1.0% 0.13

10 15 Event rate (%) 10 TIDES-ACS MACE at 12 months BAS OPTIMAX-BAS (n=989) (989) EES SYNERGY-EES (n=502) (502) P = 0.66 HR (95% CI) = 1.12 ( ) 5 P = 0.04 P = P = % 5.4% 3.4% 6.3% 7.0% 0 1.6% 1.8% 0.5% Cardiac death Myocardial infarction Ischemia-driven TLR MACE Definite Stent Thrombosis: 1.0% for BAS and 2.0% for EES (p=0.15)

11 15 TIDES-ACS other events at 12 months Event rate (%) 10 OPTIMAX-BAS (989) SYNERGY-EES (502) P = 0.15 P = 0.17 P = 0.80 P = % 2.0% 0.4% 1.0% 1.2% 1.0% 1.2% Definite ST Non-cardiac death Ischemia-driven TVR (non-tlr) 2.0% Major bleeding

12 TIDES-ACS ARC Stent Thrombosis at 12 months OPTIMAX BAS (n=989) n (%) SYNERGY EES (n=502) n (%) P Value Definite ST 10 (1.0) 10 (2.0) 0.15 Probable ST 1 (0.1) 4 (0.8) Definite or Probable ST 11 (1.1) 14 (2.8) 0.01

13 TIDES-ACS Co-Primary Endpoint at 18 months Patients presenting with Acute Coronary Syndrome BAS Titanium-Nitride-Oxide-coated Bioactive Stent 989 Patients 12 International Sites Randomisation 2:1 EES Everolimus-Eluting Stent with biodegradable polymer 502 Patients Clinical Follow-up 30d 6mo 12mo 18mo 2yr 3yr 4yr Clinical Co-Primary endpoint 5yr Co-Primary Superiority Endpoint: Cardiac death, MI, major bleeding at 18 months PI P Karjalainen (FIN) Co-PI K Kervinen (FIN), J van Der Heyden (NED), H Romppanen (FIN), P Tonino (NED) CEC: J Marco (FRA), A de Belder (UK), R Wiseth (NOR), J Gomez-Hospital (SPA), D Formigli (ITA) ClinicalTrials.gov: NCT Minerva Cardioangiol. 2015;63:21-9.

14 TIDES-ACS at 18 months Statistical considerations Co-Primary Superiority Endpoint at 18 months including * Myocardial Infarction (MI) * Cardiac Death * Major Bleeding - Expected event rate in SYNERGY vs. OPTIMAX; 6.5% vs. 3.5% * Sample size needed (α=5%; β=80%), N = 1484 TIDES-ACS

15 Bleeding Academic Research Consortium (BARC) Mehran et al. Circulation 2001;123: Type 3 Type 3a - Overt bleeding + hemoglobin drop of 3 to <5g/dl - Any transfusion with overt bleeding Type 3b - Overt bleeding + hemoglobin drop > 5g/dl - Cardiac tamponade - Bleeding requiring surgical intervention for control - Bleeding requiring intravenous vasoactive agents Type 3c - Intracranial hemorrhage - Subcategories confirmed by autopsy or imaging or lumbar puncture - Intraocular bleed compromising vision Type 4: CABG-related bleeding Perioperative intracranial bleeding within 48 h Reoperation after closure of sternotomy for the purpose of controlling bleeding Transfusion of >5 U whole blood or packed red blood cells within 48-h period Chest tube output >2L within a 24-h period Type 5: fatal bleeding Type 5a - Probable fatal bleeding; no autopsy or imaging confirmation but clinically suspicious Type 5b - Definite fatal bleeding; overt bleeding or autopsy or imaging confirmation

16 TIDES-ACS Co-primary* (superiority) endpoint at 18 months Co-Primary Superiority Endpoint Met % 12 OPTIMAX-BAS (n=989) SYNERGY (n=502) P = P = HR 2.17 (95% CI ) 8 Log-Rank P < % 7.8% - 4.1% % 3.7% Months after Index PCI * Co-primary endpoint = myocardial infarction (MI), cardiac death and major bleeding

17 15 TIDES-ACS MACE components at 18 months Event rate (%) 10 OPTIMAX-BAS (989) SYNERGY-EES (502) P = P = P = % P = % 5 5.0% 5.8% 4.4% 2.6% 2.2% 0 0.6% Cardiac death Myocardial infarction Ischemia-driven TLR MACE

18 15 TIDES-ACS other events at 18 months Event rate (%) 10 OPTIMAX-BAS (989) SYNERGY-EES (502) P = P = 0.14 P = 0.84 P = % 2.2% 0.5% 1.3% 1.4% % Definite ST Non-cardiac death Ischemia-driven TVR (non-tlr) 2.4% Major bleeding

19 TIDES-ACS Conclusions OPTIMAX-BAS was non-inferior to platinum-chromium-based biodegradable-polymer SYNERGY-EES for the primary composite of safety and efficacy outcome (MACE) at 12- month follow-up. Co-primary superiority endpoint at 18 months (myocardial infarction, cardiac death and major bleeding) showed better outcome with OPTIMAX-BAS compared with SYNERGY-EES TIDES-ACS

20 TIDES-ACS trial Comparison of TItanium-nitride-oxide coated bioactive stent to the Drug (everolimus)-eluting Stent in Acute Coronary Syndrome Pasi P Karjalainen