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
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