Efficacy and Safety of a Dual Ticagrelor plus Aspirin Antiplatelet - PowerPoint PPT Presentation

Efficacy and Safety of a Dual Ticagrelor plus Aspirin Antiplatelet Strategy after Coronary Artery Bypass Grafting: The DACAB Randomized Clinical Trial Qiang Zhao 1 Yunpeng Zhu 1 , Zhiyun Xu 2 , Zhaoyun Cheng 3 , Ju Mei 4 , Xin Chen 5 , Xiaowei Wang 6 1 Ruijin Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China; 2 Changhai Hospital of Shanghai, Shanghai, China; 3 Henan Provincial People's Hospital, Zhengzhou, China; 4 Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; 5 Nanjing First Hospital, Nanjing, China; 6 Jiangsu Province Hospital, Nanjing, China

Disclosures  Qiang Zhao declares that he has served as a speaker for AstraZeneca, Medtronic, and Johnson & Johnson, and has been an investigator on clinical trials sponsored by AstraZeneca, Novartis, Sanofi, and Bayer  Yunpeng Zhu has been an investigator on clinical trials sponsored by AstraZeneca, Novartis, Sanofi, and Bayer  Zhiyun Xu has served as a speaker for Medtronic  Zhaoyun Cheng has served as a speaker for AstraZeneca, and Medtronic  Ju Mei has served as a speaker for AstraZeneca, and Medtronic  Xin Chen has served as a speaker for AstraZeneca, and Johnson & Johnson, and has been an investigator on clinical trials sponsored by Bayer  Xiaowei Wang has served as a speaker for AstraZeneca, and Johnson & Johnson

Background  Currently the saphenous vein graft (SVG) is sill the most commonly used in CABG  However, the SVG failure rate is 10 – 25% at 1 year and 50% at 10 years post-CABG  Dual antiplatelet therapy (DAPT) reduces MACE in patients with ACS who undergo CABG, but data regarding SVG patency is limited  Effects of dual ticagrelor plus aspirin therapy on graft patency has been evaluated in a small pilot study that was terminated early because of low recruitment

Objective  Compare the efficacy and safety of combination ticagrelor plus aspirin therapy (T+A) or ticagrelor monotherapy (T) with aspirin monotherapy (A) on SVG patency 1 year after elective CABG

Study Design  Randomized (1:1:1), multicentre, open-label Ticagrelor 90 mg bid +Aspirin 100 mg qd Restart time: within 24 hours post CABG Screening for eligibility Ticagrelor 90 mg bid Restart time: within 24 hours post CABG CABG R Aspirin 100 mg qd Restart time: within 24 hours post CABG 5 ± 1d 9 ± 2d 30 ± 7d 90 ± 7d 180 ± 14d 360 ± 14d Time 1d 2d 3d Haematology X X X X X X X X X ECG X X X X X X X X X UCG X X X MSCTA or CAG X X

Patient Selection Criteria Inclusion Criteria • Age 18-80 years • Indication for CABG Major Exclusion Criteria • Risk of serious bleeding • Cardiogenic shock, (eg: history of ICH, bleeding hemodynamic instability • diathesis within 3m, or GI bleed Need for urgent or within 1 y) concomitant cardiac surgery • • Contraindication to study meds Need for DAPT or VKA

Angina Outcomes  Primary outcome  SVG patency at 1y by MSCTA/CAG (ITT)  Secondary outcomes  SVG patency at 7d  MACE within 1y  Recurrence of angina within 1y  Atrial fibrillation within 7d  Bleeding (TIMI criteria) within 1y

Patient Disposition Randomized to treatment n = 500 Ticagrelor plus Aspirin Ticagrelor Aspirin n = 168 n = 166 n = 166 Received ≥ 1 dose of ticagrelor Received ≥ 1 dose of ticagrelor Received ≥ 1 dose of aspirin plus aspirin ITT population ITT population ITT population n = 166 n = 166 n = 168 Patients assessed by MSCTA/CAG Patients assessed by MSCTA/CAG Patients assessed by MSCTA/CAG 1-year post-CABG 1-year post-CABG 1-year post-CABG n = 158 (94.1%) n = 156 (94.0%) n = 153 (92.2%) Reasons for missing assessment: Reasons for missing assessment: Reasons for missing assessment: Death 2 Death 0 Death 3 Loss to follow-up 0 Loss to follow-up 0 Loss to follow-up 0 Patient decision 8 Patient decision 10 Patient decision 10 Saphenous vein grafts assessed: Saphenous vein grafts assessed: Saphenous vein grafts assessed: 462/487 (94.9%) 460/488 (94.3%) 447/485 (92.2%)

Baseline Characteristics T+A T alone A alone Characteristics (n=168) (n=166) (n=166) Mean age (SD), y 63.5 (8.2) 63.3 (8.3) 64.0 (8.1) Male gender, n (%) 134 (79.8) 134 (80.7) 141 (84.9) Status SA, n (%) 55 (32.7) 63 (38.0) 50 (30.1) UA, n (%) 108 (64.3) 97 (58.4) 109 (65.7) NSTEMI, n (%) 5 (3.0) 6 (3.6) 7 (4.2) Hx MI, n (%) 53 (31.6) 60 (36.1) 43 (25.9) Hypertension, n (%) 127 (75.6) 122 (73.5) 120 (72.3) Diabetes mellitus, n (%) 75 (44.6) 75 (45.2) 67 (40.4) Hyperlipidemia, n (%) 121 (72.0) 124 (74.7) 119 (71.7) Smoking, n (%) 85 (50.6) 74 (44.6) 87 (52.4)

Baseline Characteristics T+A T alone A alone Characteristics (n=168) (n=166) (n=166) LVEF (%, median) 61.0 62.0 63.0 0 – 22 18 (10.7) 21 (12.7) 31 (18.7) SYNTAX 23 – 32 93 (55.4) 83 (50.0) 98 (59.0) Score, n (%) ≥ 33 57 (33.9) 62 (37.4) 37 (22.3) 0 – 2 71 (42.3) 63 (38.0) 64 (38.6) EuroScore, 3 – 5 n (%) 65 (38.7) 82 (49.4) 82 (49.4) ≥ 6 32 (19.0) 21 (12.7) 20 (12.0) CPB use, n (%) 39 (23.2) 36 (21.7) 46 (27.7) Grafts/case, n 3.7 3.8 3.8 SVG total, n 485 487 488 SVG/case, n 2.9 2.9 2.9

SVG Outcomes at 1 year (ITT) Patency (Fitzgibbon A) Non-occlusion (Fitzgibbon A + B) 89.9% 88.7% 100 100 86.1% 82.8% 80.6% 76.5% 80 80 SVG, % 60 60 40 40 20 20 432 371 404 438 391 420 487 485 488 487 485 488 0 0 1 2 3 1 2 3 T A T+A T A T+A T+A vs A: Δ = 12.2% (5.2, 19.2) P = .0006 T+A vs A: Δ = 9.3% (2.7, 16.0) P = .0060 T vs A: Δ = 6.3% ( – 1.1, 13.7) P = .0962 T vs A: Δ = 5.4% ( – 1.5, 12.4) P = .1264

SVG Outcomes at 1 year (PP) Patency (Fitzgibbon A) Non-occlusion (Fitzgibbon A+B) 93.7% 95.0% 100 100 91.0% 87.6% 87.6% 83.3% 80 80 SVG, % 60 60 40 40 20 20 429 363 390 435 382 405 458 436 445 458 436 445 0 0 1 2 3 T A T+A T A T+A T+A vs A: Δ = 10.4% (4.7, 16.2) P =.0004 T+A vs A: Δ = 7.4% (2.3, 12.4) P =.0045 T vs A: Δ = 4.3% ( -1.9, 10.7) P =.1719 T vs A: Δ = 3.4% ( -2.1, 8.9) P =.2226

MACE T+A (n=168) 6 T (n=166) 5.4 A (n=166) 5 Patients, % 4 3 2.4 2.4 2 1.8 1.8 1.2 1.2 1.2 1.2 1 0.6 3 4 9 1 2 2 2 3 2 4 0 0 168 166 166 168 166 168 166 166 166 166 0 All CV death MI Stroke

Bleeding T+A T alone A alone Bleeding Event, n (%) (n=168) (n=166) (n=166) CABG-related 1 (0.6) 1 (0.6) 0 Non-CABG-related 51 (30.4) 20 (12.1) 15 (9.0) Major 2 (1.2) 1 (0.6) 0 Minor 2 (1.2) 0 2 (1.2) Minimal 48 (28.6) 19 (11.4) 13 (7.8) Major bleeding a 3 (1.8) 2 (1.2) 0 a. Major bleeding: CABG-related plus Non-CABG-related major

Conclusions  Ticagrelor plus aspirin combination therapy significantly improves SVG patency 1-year after CABG when compared with aspirin monotherapy without excess risk of major bleeding