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 Zhao1 Yunpeng Zhu1, Zhiyun Xu2, Zhaoyun Cheng3, Ju Mei4, Xin Chen5, Xiaowei Wang6

1Ruijin Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China; 2Changhai Hospital of Shanghai, Shanghai, China; 3Henan Provincial People's Hospital, Zhengzhou, China; 4Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; 5Nanjing First Hospital, Nanjing, China; 6Jiangsu 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 Ticagrelor 90 mg bid Restart time: within 24 hours post CABG Aspirin 100 mg qd Restart time: within 24 hours post CABG

Screening for eligibility CABG

R

Haematology ECG UCG MSCTA or CAG Time 1d 2d 3d 5±1d 9±2d 90±7d 30±7d 180±14d 360±14d X X X X X X X X X X X X X X X X X X X X X X X

Patient Selection Criteria

Inclusion Criteria

• Age 18-80 years

Major Exclusion Criteria

• Cardiogenic shock,

hemodynamic instability

• Need for urgent or

concomitant cardiac surgery

• Need for DAPT or VKA
• Risk of serious bleeding

(eg: history of ICH, bleeding diathesis within 3m, or GI bleed within 1 y)

• Contraindication to study meds
• Indication for CABG

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

Angina

Patient Disposition

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

Baseline Characteristics

Characteristics T+A (n=168) T alone (n=166) A alone (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

Characteristics T+A (n=168) T alone (n=166) A alone (n=166)

LVEF (%, median) 61.0 62.0 63.0 SYNTAX Score, n (%) 0–22 18 (10.7) 21 (12.7) 31 (18.7) 23–32 93 (55.4) 83 (50.0) 98 (59.0) ≥33 57 (33.9) 62 (37.4) 37 (22.3) EuroScore, n (%) 0–2 71 (42.3) 63 (38.0) 64 (38.6) 3–5 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)

Non-occlusion (Fitzgibbon A + B)

20 40 60 80 100

1 2 3

371 485 404 488 432 487

T+A T A

T+A vs A: Δ = 12.2% (5.2, 19.2) P = .0006 T vs A: Δ = 6.3% (–1.1, 13.7) P = .0962 20 40 60 80 100

1 2 3

88.7% 76.5% 82.8%

T+A T A

391 485 438 487 420 488

T+A vs A: Δ = 9.3% (2.7, 16.0) P = .0060 T vs A: Δ = 5.4% (–1.5, 12.4) P = .1264 89.9% 80.6% 86.1%

SVG, % Patency (Fitzgibbon A)

20 40 60 80 100 20 40 60 80 100

1 2 3

SVG Outcomes at 1 year (PP)

Patency (Fitzgibbon A) Non-occlusion (Fitzgibbon A+B) SVG, % T+A T A

T+A vs A: Δ = 10.4% (4.7, 16.2) P=.0004 T vs A: Δ = 4.3% (-1.9, 10.7) P=.1719

T+A T A

T+A vs A: Δ = 7.4% (2.3, 12.4) P=.0045 T vs A: Δ = 3.4% (-2.1, 8.9) P=.2226 93.7% 83.3% 87.6%

363 436 429 458 390 445 382 436 435 458 405 445

95.0% 87.6% 91.0%

1.8 0.6 1.2 2.4 1.2 1.2 5.4 1.2 1.8 2.4

1 2 3 4 5 6 All CV death MI Stroke

MACE

Patients, %

9 166 2 166 3 166 4 166 4 166 2 166 2 166 3 168 1 168 2 168

T+A (n=168) T (n=166) A (n=166)

Bleeding

Bleeding Event, n (%) T+A (n=168) T alone (n=166) A alone (n=166)

CABG-related 1 (0.6) 1 (0.6) Non-CABG-related 51 (30.4) 20 (12.1) 15 (9.0) Major 2 (1.2) 1 (0.6) Minor 2 (1.2) 2 (1.2) Minimal 48 (28.6) 19 (11.4) 13 (7.8) Major bleedinga 3 (1.8) 2 (1.2)

• 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