Is administration of dual-antiplatelet therapy beneficial for patients following off-pump coronary artery bypass grafting?

Is administration of dual-antiplatelet therapy beneficial for patients following off-pump... Abstract A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether administration of dual-antiplatelet therapy (DAPT) following off-pump coronary artery bypass grafting (OPCAB) would improve postoperative clinical outcomes or minimize the incidence of postoperative graft failure. In total, 101 papers were found using the reported search, 14 of which represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. One meta-analysis and 3 randomized controlled trials showed that DAPT following OPCAB is associated with decreased incidence of saphenous vein graft occlusion. One randomized controlled trial and 4 observational studies showed no effect of DAPT on mortality following OPCAB, whereas 3 observational studies showed that DAPT decreased mortality. One meta-analysis and 4 observational studies showed that DAPT reduced the incidence of cardiac events following OPCAB. One randomized controlled trial and 4 observational studies showed that DAPT did not increase the incidence of major or minor bleeding complications following OPCAB. The results presented suggest that administration of DAPT in patients following OPCAB for at least 3 months improves saphenous vein graft patency and could be protective against recurrence of cardiac events, especially acute coronary syndrome, in comparison with aspirin monotherapy. The administration of DAPT following OPCAB is safe and is not associated with increased incidence of major or minor bleeding complications when compared with aspirin alone. Dual-antiplatelet therapy , Off-pump coronary artery bypass grafting , Outcomes INTRODUCTION A best evidence topic was constructed according to a structured protocol. This is fully described in the ICVTS [1]. THREE-PART QUESTION Is [dual-antiplatelet therapy] beneficial for patients following [off-pump coronary artery bypass grafting] in terms of [graft failure and clinical outcomes]? CLINICAL SCENARIO You performed an elective off-pump coronary artery bypass grafting (OPCAB) to a 60-year-old man with multi-vessel coronary artery disease and diabetes. You administer aspirin 6-h following surgery and plan to continue this for life. A colleague remarks that OPCAB is related to a significant increase in overall graft occlusion when compared with on-pump coronary artery bypass grafting (CABG) and wonders whether administration of dual-antiplatelet therapy (DAPT) might improve graft patency or clinical outcomes. You resolve to search the literature yourself. SEARCH STRATEGY The literature was reviewed by searching MEDLINE from 1950 to October 2017 using PubMed interface: ((OPCAB OR off-pump OR off-pump OR off-pump OR beating heart)) AND ((DAPT OR dual-antiplatelet therapy) OR ((aspirin) AND (platelet aggregation inhibitors OR clopidogrel OR ticagrelor OR prasugrel))). In addition, similar searches were performed in EMBASE and Cochrane Central Registry of Controlled Trials. SEARCH OUTCOME One hundred and one papers were found using the reported search. From these, 14 papers were identified, which provided the best evidence to answer the clinical question. These are presented in Table 1. Table 1: Best evidence papers Author, date, journal and country Study type (level of evidence) Patient group Outcomes Key results Comments Deo et al. (2013), J Card Surg, USA [2] Meta-analysis (level 1) n = 1275 2 RCTs + 2 observational studies DAPT: aspirin + clopidogrel 75 mg/day n = 688 patients Control: aspirin n = 587 patients Perioperative adverse cardiac events defined as perioperative angina or MI Angiographic outcomes at follow-up Perioperative adverse cardiac events DAPT vs Control RR 0.29, 95% CI 0.11–0.72; P = 0.008 Angiographic outcomes SVG DAPT vs Control RR 0.45; 95% CI 0.21–0.98; P = 0.04 Mannacio et al. (2012), Heart, Italy [3] Randomized controlled trial (level 2a) n = 300 DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 150 patients Control: aspirin 100 mg/day n = 150 patients DAPT continued for 12 months Antiplatelet drugs administered when postoperative chest drainage was < 50 ml/h for 2 consecutive hours Clinical and angiographic outcomes at mean follow-up: 12 months Bleeding complications DAPT was a strong predictor of SVG patency (RR 5.1, 95% CI 1.4–16.3; P < 0.01) Major bleeding DAPT vs Control 1.3% vs 1.3% (P = 1) Minor bleeding DAPT vs Control 2% vs 1.3% (P = 0.5) MI DAPT vs Control 2% vs 4% (P = 0.5) Coronary reintervention DAPT vs Control 0.6% vs 1.3% (P = 0.5) Mortality DAPT vs Control 0.6% vs 1.3% (P = 0.5) Angiographic outcomes (percent of the occluded grafts) LIMA DAPT vs Control 1.4% vs 2.1% (P = 0.5) RIMA DAPT vs Control 0% vs 2.8% (P = 0.5) RA DAPT vs Control 3.5% vs 0% (P = 0.5) SVG DAPT vs Control 7.4% vs 13.1% (P = 0.04) Total occluded grafts DAPT vs Control 15.2% vs 27% (P = 0.02) Gao et al. (2010), J Am Coll Cardiol, China [4] Randomized controlled trial (level 2a) n = 224 patients who underwent on-pump CABG or OPCAB 58.4% of the patients underwent OPCAB DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 113 patients Control: aspirin 100 mg/day n = 111 patients DAPT continued for 3 months Antiplatelet drugs administered when postoperative chest drainage was <30 ml/h for 2 consecutive hours Angiographic outcomes at mean follow-up: 3 months Angiographic outcomes (percent of the occluded grafts) Multivariate analysis showed that DAPT independently increased venous graft patency (RR 1.996, 95% CI 1.015–3.922; P = 0.045) LIMA DAPT vs Control 1.8% vs 0.9% (P = 0.583) RA DAPT vs Control 25% vs 33.3% (P = 0.809) SVG DAPT vs Control 8.4% vs 14.3% (P = 0.043) Total occluded grafts DAPT vs Control 6.5% vs 10.3% (P = 0.07) Mujanovic et al. (2009), Innovations (Phila), Bosnia [5] Randomized controlled trial (level 2a) n = 20 DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 10 patients Control: aspirin 100 mg/day n = 10 patients DAPT continued for 3 months Angiographic outcomes at follow-up: 3 months Angiographic outcomes (percent of the occluded grafts) LIMA DAPT vs Control 0% vs 0% SVG DAPT vs Control 10.52% vs 47.05% (P < 0.05) Total occluded grafts DAPT vs Control 6.89% vs 29.62% (P = 0.037) Wang et al. (2014), J Biomed Res, China [6] Randomized controlled trial (level 2a) n = 60 DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 28 patients Control: aspirin 100 mg/day n = 29 patients Cardiac events defined as: death, MI and heart failure In-hospital cardiac events DAPT vs Control 7.14% vs 10.34% (P > 0.05) Benedetto et al. (2017), Eur J Cardiothorac Surg, UK [7] Observational study (level 2b) n = 1190 DAPT: aspirin + clopidogrel n = 430 Control: aspirin n = 760 MACCE defined as occurrence of cardiovascular death, MI, either ST elevation MI or non-ST-elevation MI, cerebrovascular accident or repeat revascularization Follow-up: 12 months MACCE at follow-up DAPT vs Control HR 0.90, 95% CI 0.50–1.63; P  = 0.73 Cardiovascular death, MI or cerebrovascular accident DAPT vs Control HR 0.53, 95% CI 0.25–1.11; P  = 0.09 Prates et al. (2016), Braz J Cardiovasc Surg, USA [8] Observational study (level 2b) n = 790 DAPT: aspirin + clopidogrel n = 378 Control: aspirin n = 412 Follow-up: 12 months Mortality at 1 year DAPT vs Control 2.6% vs 4.9% (P > 0.05) Ebrahimi et al. (2014), Ann Thorac Surg, USA [9] Observational study (level 2b) n = 489 DAPT: aspirin + clopidogrel (doses not demonstrated) n = 221 patients Control: aspirin (doses not demonstrated) n = 268 patients Angiographic outcome at 1-year follow-up Angiographic outcomes (percent of the occluded grafts) SVG DAPT vs Control 15.5% vs 17.4% (P = 0.56) López et al. (2013), J Card Surg, Spain [10] Observational study (level 2b) n = 237 DAPT: aspirin 100 mg/day +  clopidogrel 75 mg/day n = 109 patients Control: aspirin 100 mg/day n = 128 patients Clinical outcomes at mean follow-up: 23.85 + 0.5 months Bleeding complications Multivariate analysis showed that DAPT was an independent protective factor in the occurrence of cardiac events (HR 0.395, 95% CI 0.176–0.885; P = 0.024) Major bleeding DAPT vs Control 0.9% vs 0.8% (P = 0.909) Minor bleeding DAPT vs Control 3.7% vs 2.3% (P = 0.548) Acute coronary syndrome DAPT vs Control 3.7% vs 10.9% (P = 0.035) Coronary reintervention DAPT vs Control 4.6% vs 5.5% (P = 0.758) Cardiovascular death DAPT vs Control 1.8% vs 4.7% (P = 0.226) Williams et al. (2013), J Thromb Thrombolysis, USA [11] Observational (level 2b) n = 631 DAPT: aspirin + clopidogrel (doses not demonstrated) n = 212 patients Control: aspirin (doses not demonstrated) n = 419 patients Clinical outcomes at follow-up: 5 years Mortality DAPT vs Control HR 0.40, 95% CI 0.2–0.80; P < 0.05 Mortality or MI DAPT vs Control HR 0.53, 95% CI 0.30–0.94; P < 0.05 Mortality, MI or revascularization DAPT vs Control HR 0.75, 95% CI 0.51–1.11; P > 0.05 Kim et al. (2009), J Thorac Cardiovasc Surg, USA [12] Observational study (level 2b) n = 4419 DAPT: aspirin + clopidogrel (doses not demonstrated) n = 1567 patients Control: aspirin (doses not demonstrated) n = 2852 patients Ischaemic or thrombotic events are defined as postoperative acute MI, stroke and venous thromboembolism Any bleeding events defined as post-procedural haemorrhage or haematoma and gastrointestinal haemorrhage Clinical outcomes at follow-up: 30 days Any bleeding events DAPT vs Control 3.64% vs 4.94% (P < 0.05) Any ischaemic or thrombotic events DAPT vs Control 1.21% vs 2.03% (P > 0.05) In-hospital mortality DAPT vs Control 1.08% vs 2.35% (P > 0.05) Gurbuz et al. (2006), Eur J Cardiothorac Surg, Turkey, USA [13] Observational study (level 2b) n = 591 DAPT: aspirin 81 mg/day +  clopidogrel 75 mg/day n = 325 patients Control: aspirin 325 mg/day n = 266 patients DAPT continued for 30 days or longer DAPT administered on the 1st postoperative day Clinical outcomes at mean follow-up: 37.7 + 13.4 months Bleeding complications DAPT independently decreased adverse cardiac events (OR 0.2, 95% CI 0.10–0.45; P < 0.0001) The use of DAPT >30 days following OPCAB did not further improve the outcomes Major bleeding DAPT vs Control 0.6% vs 0.75% (P = 0.8) Minor bleeding DAPT vs Control 1.5% vs 3% Recurrent angina DAPT vs Control 1.8% vs 8.6% (P < 0.0001) MI DAPT vs Control 0% vs 3.4% (P < 0.001) Coronary reintervention DAPT vs Control 0.6% vs 6.8% (P < 0.0001) Mortality DAPT vs Control 2.2% vs 8.3% (P < 0.0001) Halkos et al. (2006), Ann Thorac Surg, USA [14] Observational study (level 2b) n = 364 DAPT: aspirin + 75 mg clopidogrel n = 193 patients Control: aspirin n = 171 patients Clopidogrel administered 4-h after surgery if chest drainage was <100 ml/h DAPT continued for 4 weeks Cardiac events defined as new-onset or unstable angina, ST-elevation or non-ST-elevation MI and coronary reintervention Bleeding complications Major bleeding DAPT vs Control 1.1% vs 0% (P > 0.05) Minor bleeding DAPT vs Control 1.1% vs 0.7% (P > 0.05) Mortality 30 Days DAPT vs Control 1.6% vs 3.5% (P > 0.05) 6 Months DAPT vs Control 3.4% vs 0.6% (P > 0.05) Cardiac events 30 Days DAPT vs Control 0% vs 0.7% (P > 0.05) 6 Months DAPT vs Control 1.7% vs 3.3% (P > 0.05) Cerebrovascular events 30 Days DAPT vs Control 0.6% vs 0% (P > 0.05) 6 Months DAPT vs Control 1.7% vs 2% (P > 0.05) Ibrahim et al. (2006), Heart Surg Forum, Norway [15] Observational study (level 2b) n = 94 DAPT: aspirin 75–160 mg + 75 mg clopidogrel Control: aspirin 75–160 mg DAPT continued for 4 weeks Angiographic outcomes in 62 patients (64%) at follow-up: 185 + 92 days Angiographic outcomes (percent of the occluded grafts) LIMA DAPT vs Control 4% vs 8% (P > 0.5) SVG DAPT vs Control 13% vs 34% (P > 0.5) Total occluded grafts DAPT vs Control 7% vs 16% (P > 0.5) Author, date, journal and country Study type (level of evidence) Patient group Outcomes Key results Comments Deo et al. (2013), J Card Surg, USA [2] Meta-analysis (level 1) n = 1275 2 RCTs + 2 observational studies DAPT: aspirin + clopidogrel 75 mg/day n = 688 patients Control: aspirin n = 587 patients Perioperative adverse cardiac events defined as perioperative angina or MI Angiographic outcomes at follow-up Perioperative adverse cardiac events DAPT vs Control RR 0.29, 95% CI 0.11–0.72; P = 0.008 Angiographic outcomes SVG DAPT vs Control RR 0.45; 95% CI 0.21–0.98; P = 0.04 Mannacio et al. (2012), Heart, Italy [3] Randomized controlled trial (level 2a) n = 300 DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 150 patients Control: aspirin 100 mg/day n = 150 patients DAPT continued for 12 months Antiplatelet drugs administered when postoperative chest drainage was < 50 ml/h for 2 consecutive hours Clinical and angiographic outcomes at mean follow-up: 12 months Bleeding complications DAPT was a strong predictor of SVG patency (RR 5.1, 95% CI 1.4–16.3; P < 0.01) Major bleeding DAPT vs Control 1.3% vs 1.3% (P = 1) Minor bleeding DAPT vs Control 2% vs 1.3% (P = 0.5) MI DAPT vs Control 2% vs 4% (P = 0.5) Coronary reintervention DAPT vs Control 0.6% vs 1.3% (P = 0.5) Mortality DAPT vs Control 0.6% vs 1.3% (P = 0.5) Angiographic outcomes (percent of the occluded grafts) LIMA DAPT vs Control 1.4% vs 2.1% (P = 0.5) RIMA DAPT vs Control 0% vs 2.8% (P = 0.5) RA DAPT vs Control 3.5% vs 0% (P = 0.5) SVG DAPT vs Control 7.4% vs 13.1% (P = 0.04) Total occluded grafts DAPT vs Control 15.2% vs 27% (P = 0.02) Gao et al. (2010), J Am Coll Cardiol, China [4] Randomized controlled trial (level 2a) n = 224 patients who underwent on-pump CABG or OPCAB 58.4% of the patients underwent OPCAB DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 113 patients Control: aspirin 100 mg/day n = 111 patients DAPT continued for 3 months Antiplatelet drugs administered when postoperative chest drainage was <30 ml/h for 2 consecutive hours Angiographic outcomes at mean follow-up: 3 months Angiographic outcomes (percent of the occluded grafts) Multivariate analysis showed that DAPT independently increased venous graft patency (RR 1.996, 95% CI 1.015–3.922; P = 0.045) LIMA DAPT vs Control 1.8% vs 0.9% (P = 0.583) RA DAPT vs Control 25% vs 33.3% (P = 0.809) SVG DAPT vs Control 8.4% vs 14.3% (P = 0.043) Total occluded grafts DAPT vs Control 6.5% vs 10.3% (P = 0.07) Mujanovic et al. (2009), Innovations (Phila), Bosnia [5] Randomized controlled trial (level 2a) n = 20 DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 10 patients Control: aspirin 100 mg/day n = 10 patients DAPT continued for 3 months Angiographic outcomes at follow-up: 3 months Angiographic outcomes (percent of the occluded grafts) LIMA DAPT vs Control 0% vs 0% SVG DAPT vs Control 10.52% vs 47.05% (P < 0.05) Total occluded grafts DAPT vs Control 6.89% vs 29.62% (P = 0.037) Wang et al. (2014), J Biomed Res, China [6] Randomized controlled trial (level 2a) n = 60 DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 28 patients Control: aspirin 100 mg/day n = 29 patients Cardiac events defined as: death, MI and heart failure In-hospital cardiac events DAPT vs Control 7.14% vs 10.34% (P > 0.05) Benedetto et al. (2017), Eur J Cardiothorac Surg, UK [7] Observational study (level 2b) n = 1190 DAPT: aspirin + clopidogrel n = 430 Control: aspirin n = 760 MACCE defined as occurrence of cardiovascular death, MI, either ST elevation MI or non-ST-elevation MI, cerebrovascular accident or repeat revascularization Follow-up: 12 months MACCE at follow-up DAPT vs Control HR 0.90, 95% CI 0.50–1.63; P  = 0.73 Cardiovascular death, MI or cerebrovascular accident DAPT vs Control HR 0.53, 95% CI 0.25–1.11; P  = 0.09 Prates et al. (2016), Braz J Cardiovasc Surg, USA [8] Observational study (level 2b) n = 790 DAPT: aspirin + clopidogrel n = 378 Control: aspirin n = 412 Follow-up: 12 months Mortality at 1 year DAPT vs Control 2.6% vs 4.9% (P > 0.05) Ebrahimi et al. (2014), Ann Thorac Surg, USA [9] Observational study (level 2b) n = 489 DAPT: aspirin + clopidogrel (doses not demonstrated) n = 221 patients Control: aspirin (doses not demonstrated) n = 268 patients Angiographic outcome at 1-year follow-up Angiographic outcomes (percent of the occluded grafts) SVG DAPT vs Control 15.5% vs 17.4% (P = 0.56) López et al. (2013), J Card Surg, Spain [10] Observational study (level 2b) n = 237 DAPT: aspirin 100 mg/day +  clopidogrel 75 mg/day n = 109 patients Control: aspirin 100 mg/day n = 128 patients Clinical outcomes at mean follow-up: 23.85 + 0.5 months Bleeding complications Multivariate analysis showed that DAPT was an independent protective factor in the occurrence of cardiac events (HR 0.395, 95% CI 0.176–0.885; P = 0.024) Major bleeding DAPT vs Control 0.9% vs 0.8% (P = 0.909) Minor bleeding DAPT vs Control 3.7% vs 2.3% (P = 0.548) Acute coronary syndrome DAPT vs Control 3.7% vs 10.9% (P = 0.035) Coronary reintervention DAPT vs Control 4.6% vs 5.5% (P = 0.758) Cardiovascular death DAPT vs Control 1.8% vs 4.7% (P = 0.226) Williams et al. (2013), J Thromb Thrombolysis, USA [11] Observational (level 2b) n = 631 DAPT: aspirin + clopidogrel (doses not demonstrated) n = 212 patients Control: aspirin (doses not demonstrated) n = 419 patients Clinical outcomes at follow-up: 5 years Mortality DAPT vs Control HR 0.40, 95% CI 0.2–0.80; P < 0.05 Mortality or MI DAPT vs Control HR 0.53, 95% CI 0.30–0.94; P < 0.05 Mortality, MI or revascularization DAPT vs Control HR 0.75, 95% CI 0.51–1.11; P > 0.05 Kim et al. (2009), J Thorac Cardiovasc Surg, USA [12] Observational study (level 2b) n = 4419 DAPT: aspirin + clopidogrel (doses not demonstrated) n = 1567 patients Control: aspirin (doses not demonstrated) n = 2852 patients Ischaemic or thrombotic events are defined as postoperative acute MI, stroke and venous thromboembolism Any bleeding events defined as post-procedural haemorrhage or haematoma and gastrointestinal haemorrhage Clinical outcomes at follow-up: 30 days Any bleeding events DAPT vs Control 3.64% vs 4.94% (P < 0.05) Any ischaemic or thrombotic events DAPT vs Control 1.21% vs 2.03% (P > 0.05) In-hospital mortality DAPT vs Control 1.08% vs 2.35% (P > 0.05) Gurbuz et al. (2006), Eur J Cardiothorac Surg, Turkey, USA [13] Observational study (level 2b) n = 591 DAPT: aspirin 81 mg/day +  clopidogrel 75 mg/day n = 325 patients Control: aspirin 325 mg/day n = 266 patients DAPT continued for 30 days or longer DAPT administered on the 1st postoperative day Clinical outcomes at mean follow-up: 37.7 + 13.4 months Bleeding complications DAPT independently decreased adverse cardiac events (OR 0.2, 95% CI 0.10–0.45; P < 0.0001) The use of DAPT >30 days following OPCAB did not further improve the outcomes Major bleeding DAPT vs Control 0.6% vs 0.75% (P = 0.8) Minor bleeding DAPT vs Control 1.5% vs 3% Recurrent angina DAPT vs Control 1.8% vs 8.6% (P < 0.0001) MI DAPT vs Control 0% vs 3.4% (P < 0.001) Coronary reintervention DAPT vs Control 0.6% vs 6.8% (P < 0.0001) Mortality DAPT vs Control 2.2% vs 8.3% (P < 0.0001) Halkos et al. (2006), Ann Thorac Surg, USA [14] Observational study (level 2b) n = 364 DAPT: aspirin + 75 mg clopidogrel n = 193 patients Control: aspirin n = 171 patients Clopidogrel administered 4-h after surgery if chest drainage was <100 ml/h DAPT continued for 4 weeks Cardiac events defined as new-onset or unstable angina, ST-elevation or non-ST-elevation MI and coronary reintervention Bleeding complications Major bleeding DAPT vs Control 1.1% vs 0% (P > 0.05) Minor bleeding DAPT vs Control 1.1% vs 0.7% (P > 0.05) Mortality 30 Days DAPT vs Control 1.6% vs 3.5% (P > 0.05) 6 Months DAPT vs Control 3.4% vs 0.6% (P > 0.05) Cardiac events 30 Days DAPT vs Control 0% vs 0.7% (P > 0.05) 6 Months DAPT vs Control 1.7% vs 3.3% (P > 0.05) Cerebrovascular events 30 Days DAPT vs Control 0.6% vs 0% (P > 0.05) 6 Months DAPT vs Control 1.7% vs 2% (P > 0.05) Ibrahim et al. (2006), Heart Surg Forum, Norway [15] Observational study (level 2b) n = 94 DAPT: aspirin 75–160 mg + 75 mg clopidogrel Control: aspirin 75–160 mg DAPT continued for 4 weeks Angiographic outcomes in 62 patients (64%) at follow-up: 185 + 92 days Angiographic outcomes (percent of the occluded grafts) LIMA DAPT vs Control 4% vs 8% (P > 0.5) SVG DAPT vs Control 13% vs 34% (P > 0.5) Total occluded grafts DAPT vs Control 7% vs 16% (P > 0.5) CABG: coronary artery bypass grafting; CI: confidence interval; DAPT: dual-antiplatelet therapy; HR: hazard ratio; LIMA: left internal mammary artery; MI: myocardial infarction; OPCAB: off-pump coronary artery bypass grafting; OR: odds ratio; RA: radial artery; RCT: randomized controlled trial; RIMA: right internal mammary artery; RR: relative risk; SVG: saphenous vein graft. Table 1: Best evidence papers Author, date, journal and country Study type (level of evidence) Patient group Outcomes Key results Comments Deo et al. (2013), J Card Surg, USA [2] Meta-analysis (level 1) n = 1275 2 RCTs + 2 observational studies DAPT: aspirin + clopidogrel 75 mg/day n = 688 patients Control: aspirin n = 587 patients Perioperative adverse cardiac events defined as perioperative angina or MI Angiographic outcomes at follow-up Perioperative adverse cardiac events DAPT vs Control RR 0.29, 95% CI 0.11–0.72; P = 0.008 Angiographic outcomes SVG DAPT vs Control RR 0.45; 95% CI 0.21–0.98; P = 0.04 Mannacio et al. (2012), Heart, Italy [3] Randomized controlled trial (level 2a) n = 300 DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 150 patients Control: aspirin 100 mg/day n = 150 patients DAPT continued for 12 months Antiplatelet drugs administered when postoperative chest drainage was < 50 ml/h for 2 consecutive hours Clinical and angiographic outcomes at mean follow-up: 12 months Bleeding complications DAPT was a strong predictor of SVG patency (RR 5.1, 95% CI 1.4–16.3; P < 0.01) Major bleeding DAPT vs Control 1.3% vs 1.3% (P = 1) Minor bleeding DAPT vs Control 2% vs 1.3% (P = 0.5) MI DAPT vs Control 2% vs 4% (P = 0.5) Coronary reintervention DAPT vs Control 0.6% vs 1.3% (P = 0.5) Mortality DAPT vs Control 0.6% vs 1.3% (P = 0.5) Angiographic outcomes (percent of the occluded grafts) LIMA DAPT vs Control 1.4% vs 2.1% (P = 0.5) RIMA DAPT vs Control 0% vs 2.8% (P = 0.5) RA DAPT vs Control 3.5% vs 0% (P = 0.5) SVG DAPT vs Control 7.4% vs 13.1% (P = 0.04) Total occluded grafts DAPT vs Control 15.2% vs 27% (P = 0.02) Gao et al. (2010), J Am Coll Cardiol, China [4] Randomized controlled trial (level 2a) n = 224 patients who underwent on-pump CABG or OPCAB 58.4% of the patients underwent OPCAB DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 113 patients Control: aspirin 100 mg/day n = 111 patients DAPT continued for 3 months Antiplatelet drugs administered when postoperative chest drainage was <30 ml/h for 2 consecutive hours Angiographic outcomes at mean follow-up: 3 months Angiographic outcomes (percent of the occluded grafts) Multivariate analysis showed that DAPT independently increased venous graft patency (RR 1.996, 95% CI 1.015–3.922; P = 0.045) LIMA DAPT vs Control 1.8% vs 0.9% (P = 0.583) RA DAPT vs Control 25% vs 33.3% (P = 0.809) SVG DAPT vs Control 8.4% vs 14.3% (P = 0.043) Total occluded grafts DAPT vs Control 6.5% vs 10.3% (P = 0.07) Mujanovic et al. (2009), Innovations (Phila), Bosnia [5] Randomized controlled trial (level 2a) n = 20 DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 10 patients Control: aspirin 100 mg/day n = 10 patients DAPT continued for 3 months Angiographic outcomes at follow-up: 3 months Angiographic outcomes (percent of the occluded grafts) LIMA DAPT vs Control 0% vs 0% SVG DAPT vs Control 10.52% vs 47.05% (P < 0.05) Total occluded grafts DAPT vs Control 6.89% vs 29.62% (P = 0.037) Wang et al. (2014), J Biomed Res, China [6] Randomized controlled trial (level 2a) n = 60 DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 28 patients Control: aspirin 100 mg/day n = 29 patients Cardiac events defined as: death, MI and heart failure In-hospital cardiac events DAPT vs Control 7.14% vs 10.34% (P > 0.05) Benedetto et al. (2017), Eur J Cardiothorac Surg, UK [7] Observational study (level 2b) n = 1190 DAPT: aspirin + clopidogrel n = 430 Control: aspirin n = 760 MACCE defined as occurrence of cardiovascular death, MI, either ST elevation MI or non-ST-elevation MI, cerebrovascular accident or repeat revascularization Follow-up: 12 months MACCE at follow-up DAPT vs Control HR 0.90, 95% CI 0.50–1.63; P  = 0.73 Cardiovascular death, MI or cerebrovascular accident DAPT vs Control HR 0.53, 95% CI 0.25–1.11; P  = 0.09 Prates et al. (2016), Braz J Cardiovasc Surg, USA [8] Observational study (level 2b) n = 790 DAPT: aspirin + clopidogrel n = 378 Control: aspirin n = 412 Follow-up: 12 months Mortality at 1 year DAPT vs Control 2.6% vs 4.9% (P > 0.05) Ebrahimi et al. (2014), Ann Thorac Surg, USA [9] Observational study (level 2b) n = 489 DAPT: aspirin + clopidogrel (doses not demonstrated) n = 221 patients Control: aspirin (doses not demonstrated) n = 268 patients Angiographic outcome at 1-year follow-up Angiographic outcomes (percent of the occluded grafts) SVG DAPT vs Control 15.5% vs 17.4% (P = 0.56) López et al. (2013), J Card Surg, Spain [10] Observational study (level 2b) n = 237 DAPT: aspirin 100 mg/day +  clopidogrel 75 mg/day n = 109 patients Control: aspirin 100 mg/day n = 128 patients Clinical outcomes at mean follow-up: 23.85 + 0.5 months Bleeding complications Multivariate analysis showed that DAPT was an independent protective factor in the occurrence of cardiac events (HR 0.395, 95% CI 0.176–0.885; P = 0.024) Major bleeding DAPT vs Control 0.9% vs 0.8% (P = 0.909) Minor bleeding DAPT vs Control 3.7% vs 2.3% (P = 0.548) Acute coronary syndrome DAPT vs Control 3.7% vs 10.9% (P = 0.035) Coronary reintervention DAPT vs Control 4.6% vs 5.5% (P = 0.758) Cardiovascular death DAPT vs Control 1.8% vs 4.7% (P = 0.226) Williams et al. (2013), J Thromb Thrombolysis, USA [11] Observational (level 2b) n = 631 DAPT: aspirin + clopidogrel (doses not demonstrated) n = 212 patients Control: aspirin (doses not demonstrated) n = 419 patients Clinical outcomes at follow-up: 5 years Mortality DAPT vs Control HR 0.40, 95% CI 0.2–0.80; P < 0.05 Mortality or MI DAPT vs Control HR 0.53, 95% CI 0.30–0.94; P < 0.05 Mortality, MI or revascularization DAPT vs Control HR 0.75, 95% CI 0.51–1.11; P > 0.05 Kim et al. (2009), J Thorac Cardiovasc Surg, USA [12] Observational study (level 2b) n = 4419 DAPT: aspirin + clopidogrel (doses not demonstrated) n = 1567 patients Control: aspirin (doses not demonstrated) n = 2852 patients Ischaemic or thrombotic events are defined as postoperative acute MI, stroke and venous thromboembolism Any bleeding events defined as post-procedural haemorrhage or haematoma and gastrointestinal haemorrhage Clinical outcomes at follow-up: 30 days Any bleeding events DAPT vs Control 3.64% vs 4.94% (P < 0.05) Any ischaemic or thrombotic events DAPT vs Control 1.21% vs 2.03% (P > 0.05) In-hospital mortality DAPT vs Control 1.08% vs 2.35% (P > 0.05) Gurbuz et al. (2006), Eur J Cardiothorac Surg, Turkey, USA [13] Observational study (level 2b) n = 591 DAPT: aspirin 81 mg/day +  clopidogrel 75 mg/day n = 325 patients Control: aspirin 325 mg/day n = 266 patients DAPT continued for 30 days or longer DAPT administered on the 1st postoperative day Clinical outcomes at mean follow-up: 37.7 + 13.4 months Bleeding complications DAPT independently decreased adverse cardiac events (OR 0.2, 95% CI 0.10–0.45; P < 0.0001) The use of DAPT >30 days following OPCAB did not further improve the outcomes Major bleeding DAPT vs Control 0.6% vs 0.75% (P = 0.8) Minor bleeding DAPT vs Control 1.5% vs 3% Recurrent angina DAPT vs Control 1.8% vs 8.6% (P < 0.0001) MI DAPT vs Control 0% vs 3.4% (P < 0.001) Coronary reintervention DAPT vs Control 0.6% vs 6.8% (P < 0.0001) Mortality DAPT vs Control 2.2% vs 8.3% (P < 0.0001) Halkos et al. (2006), Ann Thorac Surg, USA [14] Observational study (level 2b) n = 364 DAPT: aspirin + 75 mg clopidogrel n = 193 patients Control: aspirin n = 171 patients Clopidogrel administered 4-h after surgery if chest drainage was <100 ml/h DAPT continued for 4 weeks Cardiac events defined as new-onset or unstable angina, ST-elevation or non-ST-elevation MI and coronary reintervention Bleeding complications Major bleeding DAPT vs Control 1.1% vs 0% (P > 0.05) Minor bleeding DAPT vs Control 1.1% vs 0.7% (P > 0.05) Mortality 30 Days DAPT vs Control 1.6% vs 3.5% (P > 0.05) 6 Months DAPT vs Control 3.4% vs 0.6% (P > 0.05) Cardiac events 30 Days DAPT vs Control 0% vs 0.7% (P > 0.05) 6 Months DAPT vs Control 1.7% vs 3.3% (P > 0.05) Cerebrovascular events 30 Days DAPT vs Control 0.6% vs 0% (P > 0.05) 6 Months DAPT vs Control 1.7% vs 2% (P > 0.05) Ibrahim et al. (2006), Heart Surg Forum, Norway [15] Observational study (level 2b) n = 94 DAPT: aspirin 75–160 mg + 75 mg clopidogrel Control: aspirin 75–160 mg DAPT continued for 4 weeks Angiographic outcomes in 62 patients (64%) at follow-up: 185 + 92 days Angiographic outcomes (percent of the occluded grafts) LIMA DAPT vs Control 4% vs 8% (P > 0.5) SVG DAPT vs Control 13% vs 34% (P > 0.5) Total occluded grafts DAPT vs Control 7% vs 16% (P > 0.5) Author, date, journal and country Study type (level of evidence) Patient group Outcomes Key results Comments Deo et al. (2013), J Card Surg, USA [2] Meta-analysis (level 1) n = 1275 2 RCTs + 2 observational studies DAPT: aspirin + clopidogrel 75 mg/day n = 688 patients Control: aspirin n = 587 patients Perioperative adverse cardiac events defined as perioperative angina or MI Angiographic outcomes at follow-up Perioperative adverse cardiac events DAPT vs Control RR 0.29, 95% CI 0.11–0.72; P = 0.008 Angiographic outcomes SVG DAPT vs Control RR 0.45; 95% CI 0.21–0.98; P = 0.04 Mannacio et al. (2012), Heart, Italy [3] Randomized controlled trial (level 2a) n = 300 DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 150 patients Control: aspirin 100 mg/day n = 150 patients DAPT continued for 12 months Antiplatelet drugs administered when postoperative chest drainage was < 50 ml/h for 2 consecutive hours Clinical and angiographic outcomes at mean follow-up: 12 months Bleeding complications DAPT was a strong predictor of SVG patency (RR 5.1, 95% CI 1.4–16.3; P < 0.01) Major bleeding DAPT vs Control 1.3% vs 1.3% (P = 1) Minor bleeding DAPT vs Control 2% vs 1.3% (P = 0.5) MI DAPT vs Control 2% vs 4% (P = 0.5) Coronary reintervention DAPT vs Control 0.6% vs 1.3% (P = 0.5) Mortality DAPT vs Control 0.6% vs 1.3% (P = 0.5) Angiographic outcomes (percent of the occluded grafts) LIMA DAPT vs Control 1.4% vs 2.1% (P = 0.5) RIMA DAPT vs Control 0% vs 2.8% (P = 0.5) RA DAPT vs Control 3.5% vs 0% (P = 0.5) SVG DAPT vs Control 7.4% vs 13.1% (P = 0.04) Total occluded grafts DAPT vs Control 15.2% vs 27% (P = 0.02) Gao et al. (2010), J Am Coll Cardiol, China [4] Randomized controlled trial (level 2a) n = 224 patients who underwent on-pump CABG or OPCAB 58.4% of the patients underwent OPCAB DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 113 patients Control: aspirin 100 mg/day n = 111 patients DAPT continued for 3 months Antiplatelet drugs administered when postoperative chest drainage was <30 ml/h for 2 consecutive hours Angiographic outcomes at mean follow-up: 3 months Angiographic outcomes (percent of the occluded grafts) Multivariate analysis showed that DAPT independently increased venous graft patency (RR 1.996, 95% CI 1.015–3.922; P = 0.045) LIMA DAPT vs Control 1.8% vs 0.9% (P = 0.583) RA DAPT vs Control 25% vs 33.3% (P = 0.809) SVG DAPT vs Control 8.4% vs 14.3% (P = 0.043) Total occluded grafts DAPT vs Control 6.5% vs 10.3% (P = 0.07) Mujanovic et al. (2009), Innovations (Phila), Bosnia [5] Randomized controlled trial (level 2a) n = 20 DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 10 patients Control: aspirin 100 mg/day n = 10 patients DAPT continued for 3 months Angiographic outcomes at follow-up: 3 months Angiographic outcomes (percent of the occluded grafts) LIMA DAPT vs Control 0% vs 0% SVG DAPT vs Control 10.52% vs 47.05% (P < 0.05) Total occluded grafts DAPT vs Control 6.89% vs 29.62% (P = 0.037) Wang et al. (2014), J Biomed Res, China [6] Randomized controlled trial (level 2a) n = 60 DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 28 patients Control: aspirin 100 mg/day n = 29 patients Cardiac events defined as: death, MI and heart failure In-hospital cardiac events DAPT vs Control 7.14% vs 10.34% (P > 0.05) Benedetto et al. (2017), Eur J Cardiothorac Surg, UK [7] Observational study (level 2b) n = 1190 DAPT: aspirin + clopidogrel n = 430 Control: aspirin n = 760 MACCE defined as occurrence of cardiovascular death, MI, either ST elevation MI or non-ST-elevation MI, cerebrovascular accident or repeat revascularization Follow-up: 12 months MACCE at follow-up DAPT vs Control HR 0.90, 95% CI 0.50–1.63; P  = 0.73 Cardiovascular death, MI or cerebrovascular accident DAPT vs Control HR 0.53, 95% CI 0.25–1.11; P  = 0.09 Prates et al. (2016), Braz J Cardiovasc Surg, USA [8] Observational study (level 2b) n = 790 DAPT: aspirin + clopidogrel n = 378 Control: aspirin n = 412 Follow-up: 12 months Mortality at 1 year DAPT vs Control 2.6% vs 4.9% (P > 0.05) Ebrahimi et al. (2014), Ann Thorac Surg, USA [9] Observational study (level 2b) n = 489 DAPT: aspirin + clopidogrel (doses not demonstrated) n = 221 patients Control: aspirin (doses not demonstrated) n = 268 patients Angiographic outcome at 1-year follow-up Angiographic outcomes (percent of the occluded grafts) SVG DAPT vs Control 15.5% vs 17.4% (P = 0.56) López et al. (2013), J Card Surg, Spain [10] Observational study (level 2b) n = 237 DAPT: aspirin 100 mg/day +  clopidogrel 75 mg/day n = 109 patients Control: aspirin 100 mg/day n = 128 patients Clinical outcomes at mean follow-up: 23.85 + 0.5 months Bleeding complications Multivariate analysis showed that DAPT was an independent protective factor in the occurrence of cardiac events (HR 0.395, 95% CI 0.176–0.885; P = 0.024) Major bleeding DAPT vs Control 0.9% vs 0.8% (P = 0.909) Minor bleeding DAPT vs Control 3.7% vs 2.3% (P = 0.548) Acute coronary syndrome DAPT vs Control 3.7% vs 10.9% (P = 0.035) Coronary reintervention DAPT vs Control 4.6% vs 5.5% (P = 0.758) Cardiovascular death DAPT vs Control 1.8% vs 4.7% (P = 0.226) Williams et al. (2013), J Thromb Thrombolysis, USA [11] Observational (level 2b) n = 631 DAPT: aspirin + clopidogrel (doses not demonstrated) n = 212 patients Control: aspirin (doses not demonstrated) n = 419 patients Clinical outcomes at follow-up: 5 years Mortality DAPT vs Control HR 0.40, 95% CI 0.2–0.80; P < 0.05 Mortality or MI DAPT vs Control HR 0.53, 95% CI 0.30–0.94; P < 0.05 Mortality, MI or revascularization DAPT vs Control HR 0.75, 95% CI 0.51–1.11; P > 0.05 Kim et al. (2009), J Thorac Cardiovasc Surg, USA [12] Observational study (level 2b) n = 4419 DAPT: aspirin + clopidogrel (doses not demonstrated) n = 1567 patients Control: aspirin (doses not demonstrated) n = 2852 patients Ischaemic or thrombotic events are defined as postoperative acute MI, stroke and venous thromboembolism Any bleeding events defined as post-procedural haemorrhage or haematoma and gastrointestinal haemorrhage Clinical outcomes at follow-up: 30 days Any bleeding events DAPT vs Control 3.64% vs 4.94% (P < 0.05) Any ischaemic or thrombotic events DAPT vs Control 1.21% vs 2.03% (P > 0.05) In-hospital mortality DAPT vs Control 1.08% vs 2.35% (P > 0.05) Gurbuz et al. (2006), Eur J Cardiothorac Surg, Turkey, USA [13] Observational study (level 2b) n = 591 DAPT: aspirin 81 mg/day +  clopidogrel 75 mg/day n = 325 patients Control: aspirin 325 mg/day n = 266 patients DAPT continued for 30 days or longer DAPT administered on the 1st postoperative day Clinical outcomes at mean follow-up: 37.7 + 13.4 months Bleeding complications DAPT independently decreased adverse cardiac events (OR 0.2, 95% CI 0.10–0.45; P < 0.0001) The use of DAPT >30 days following OPCAB did not further improve the outcomes Major bleeding DAPT vs Control 0.6% vs 0.75% (P = 0.8) Minor bleeding DAPT vs Control 1.5% vs 3% Recurrent angina DAPT vs Control 1.8% vs 8.6% (P < 0.0001) MI DAPT vs Control 0% vs 3.4% (P < 0.001) Coronary reintervention DAPT vs Control 0.6% vs 6.8% (P < 0.0001) Mortality DAPT vs Control 2.2% vs 8.3% (P < 0.0001) Halkos et al. (2006), Ann Thorac Surg, USA [14] Observational study (level 2b) n = 364 DAPT: aspirin + 75 mg clopidogrel n = 193 patients Control: aspirin n = 171 patients Clopidogrel administered 4-h after surgery if chest drainage was <100 ml/h DAPT continued for 4 weeks Cardiac events defined as new-onset or unstable angina, ST-elevation or non-ST-elevation MI and coronary reintervention Bleeding complications Major bleeding DAPT vs Control 1.1% vs 0% (P > 0.05) Minor bleeding DAPT vs Control 1.1% vs 0.7% (P > 0.05) Mortality 30 Days DAPT vs Control 1.6% vs 3.5% (P > 0.05) 6 Months DAPT vs Control 3.4% vs 0.6% (P > 0.05) Cardiac events 30 Days DAPT vs Control 0% vs 0.7% (P > 0.05) 6 Months DAPT vs Control 1.7% vs 3.3% (P > 0.05) Cerebrovascular events 30 Days DAPT vs Control 0.6% vs 0% (P > 0.05) 6 Months DAPT vs Control 1.7% vs 2% (P > 0.05) Ibrahim et al. (2006), Heart Surg Forum, Norway [15] Observational study (level 2b) n = 94 DAPT: aspirin 75–160 mg + 75 mg clopidogrel Control: aspirin 75–160 mg DAPT continued for 4 weeks Angiographic outcomes in 62 patients (64%) at follow-up: 185 + 92 days Angiographic outcomes (percent of the occluded grafts) LIMA DAPT vs Control 4% vs 8% (P > 0.5) SVG DAPT vs Control 13% vs 34% (P > 0.5) Total occluded grafts DAPT vs Control 7% vs 16% (P > 0.5) CABG: coronary artery bypass grafting; CI: confidence interval; DAPT: dual-antiplatelet therapy; HR: hazard ratio; LIMA: left internal mammary artery; MI: myocardial infarction; OPCAB: off-pump coronary artery bypass grafting; OR: odds ratio; RA: radial artery; RCT: randomized controlled trial; RIMA: right internal mammary artery; RR: relative risk; SVG: saphenous vein graft. RESULTS Deo et al. [2] in a meta-analysis that included 2 randomized controlled trials (RCTs) and 2 observational studies showed that administration of DAPT following OPCAB is associated with reduced risk of perioperative adverse cardiac events by 71% [relative risk (RR) 0.29, 95% confidence interval (CI) 0.11–0.72; P = 0.008]. Pooled analysis of RCTs revealed that administration of DAPT following OPCAB reduced the incidence of saphenous vein graft (SVG) occlusion by 55% (RR 0.45, 95% CI 0.21–0.98; P = 0.04). Mannacio et al. [3] in a prospective, randomized, placebo-controlled trial showed that administration of DAPT for 12 months in patients following OPCAB is associated with a significant reduction in SVG occlusion in the 1st postoperative year (7.4% vs 13.1%, P = 0.04). They also showed that DAPT was a strong predictor of SVG patency (RR 5.1, 95% CI 1.4–16.3; P < 0.01). Neither benefit nor harm of DAPT on mortality (P = 0.5), myocardial infarction (MI) (P = 0.5) or coronary reintervention (P = 0.5) was observed during the follow-up period. The authors also showed that DAPT was not associated with increased incidence of major (P = 1) or minor (P = 0.5) bleeding complications. Gao et al. [4] in a prospective RCT demonstrated that administration of DAPT for 3 months is associated with reduced incidence of SVG occlusion (8.4% vs 14.3%, P = 0.043). Multivariate analysis showed that DAPT independently increased venous graft patency (RR 1.996, 95% CI 1.015–3.922; P = 0.045). However, this group was a mixture of OPCAB (58%) and on-pump CABG. Mujanovic et al. [5] in a randomized trial showed that DAPT following OPCAB for 3 months is associated with a significant reduction in overall graft occlusion (6.89% vs 29.62%, P = 0.037). The magnitude of reduction was predominantly observed in the rate of SVG occlusion, where DAPT was associated with high reduction in SVG occlusion (10.52% vs 47.05, P < 0.05). Wang et al. [6] in a randomized trial showed no demonstrable effect of DAPT on in-hospital cardiac events in patients following OPCAB (P > 0.05). Benedetto et al. [7] in an observational analysis of patients from the Arterial Revascularization Trial (ART) showed that DAPT following OPCAB did not reduce significantly the risk of major adverse cardiovascular and cerebral events at follow-up [hazard ratio (HR) 0.90, 95% CI 0.50–1.63; P = 0.73] nor did it significantly reduce the risk for the composite of cardiovascular death, MI and cerebrovascular accidents (HR 0.53, 95% CI 0.25–1.11; P = 0.09). Prates et al. [8] in an observational study demonstrated neither benefit nor harm from DAPT as far as 1-year mortality in patients following OPCAB (P > 0.05). Ebrahimi et al. [9] in an observational analysis of patients from the ROOBY trial showed that DAPT did not significantly reduce the incidence of SVG occlusion following OPCAB at 1-year angiographic follow-up (15.5% vs 17.4%, P = 0.56). López et al. [10] in an observational trial observed that DAPT following OPCAB is not associated with increased incidence of major or minor bleeding complications (P = 0.909 and P = 0.548, respectively). They also revealed no difference in terms of coronary reintervention or cardiovascular death. However, they demonstrated that DAPT is associated with decreased incidence of acute coronary syndrome following OPCAB (3.7% vs 10.9%, P = 0.035). They also showed that DAPT was an independent protective factor in the occurrence of cardiac events (HR 0.395; 95% CI 0.176–0.885; P = 0.024). Williams et al. [11] in an observational analysis of patients from the PREVENT IV trial showed that DAPT following OPCAB is associated with reduced long-term hazard of mortality (HR 0.40; 95% CI 0.2–0.80; P < 0.05) and combined MI or mortality (HR 0.53; 95% CI 0.30–0.94; P < 0.05) but not combined MI, mortality and repeated revascularization (HR 0.75; 95% CI 0.51–1.11; P > 0.05). Kim et al. [12] in an observational study showed that DAPT following OPCAB is associated with a non-significant decrease in any ischaemic or thrombotic events (1.21% vs 2.03%, P > 0.05) and in-hospital mortality (1.08% vs 2.35%, P > 0.05) but was associated with a significantly lower incidence of bleeding events when compared with aspirin monotherapy (3.64% vs 4.94%, P < 0.05). Gurbuz et al. [13] in an observational analysis revealed that DAPT following OPCAB for at least 1 month is associated with decreased incidence of recurrent angina (P < 0.0001), MI (P < 0.001), coronary reintervention (P < 0.0001) and reduced mortality (P < 0.0001). They also showed that DAPT independently decreased adverse cardiac events by 80% (OR 0.2; 95% CI 0.10–0.45; P < 0.0001). There was no demonstrable increased incidence of major or minor bleeding complications (P = 0.8) associated with administration of DAPT in this study. Halkos et al. [14] in an observational study showed that administration of DAPT for 1 month following OPCAB is not associated with increased incidence of major (P > 0.05) or minor (P > 0.05) bleeding complications. On the other hand, neither benefit nor harm was observed in terms of mortality, cardiac or cerebrovascular events (P > 0.05). Ibrahim et al. [15] in an observational study investigated the effect of continuation of DAPT for 1 month in patients following OPCAB in terms of angiographic results. At a mean follow-up of 6 ± 3 months, there was a non-significant reduction in graft occlusion when compared with aspirin alone (7% vs 16%), which was more pronounced (yet still not significant) in terms of SVG occlusion (13% vs 34%). CLINICAL BOTTOM LINE Administration of DAPT in patients following OPCAB for at least 3 months improves SVG patency and could be protective against recurrence of cardiac events, especially acute coronary syndrome, in comparison with aspirin monotherapy. Administration of DAPT following OPCAB is safe and is not associated with increased incidence of major or minor bleeding complications when compared with aspirin alone. Conflict of interest: none declared. REFERENCES 1 Dunning J , Prendergast B , Mackway-Jones K. Towards evidence-based medicine in cardiothoracic surgery: best BETS . 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Aspirin and clopidogrel use in the early postoperative period following on-pump and off-pump coronary artery bypass grafting . J Thorac Cardiovasc Surg 2009 ; 138 : 1377 – 84 . Google Scholar CrossRef Search ADS PubMed 13 Gurbuz AT , Zia AA , Vuran AC , Cui H , Aytac A. Postoperative clopidogrel improves mid-term outcome after off-pump coronary artery bypass graft surgery: a prospective study . Eur J Cardiothorac Surg 2006 ; 29 : 190 – 5 . Google Scholar CrossRef Search ADS PubMed 14 Halkos ME , Cooper WA , Petersen R , Puskas JD , Lattouf OM , Craver JM et al. Early administration of clopidogrel is safe after off-pump coronary artery bypass surgery . Ann Thorac Surg 2006 ; 81 : 815 – 9 . Google Scholar CrossRef Search ADS PubMed 15 Ibrahim K , Tjomsland O , Halvorsen D , Wiseth R , Wahba A , Karevold A et al. Effect of clopidogrel on midterm graft patency following off-pump coronary revascularization surgery . Heart Surg Forum 2006 ; 9 : E581 – 856 . Google Scholar CrossRef Search ADS PubMed © The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Interactive CardioVascular and Thoracic Surgery Oxford University Press

Is administration of dual-antiplatelet therapy beneficial for patients following off-pump coronary artery bypass grafting?

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Oxford University Press
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© The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
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1569-9293
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1569-9285
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10.1093/icvts/ivy113
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Abstract

Abstract A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether administration of dual-antiplatelet therapy (DAPT) following off-pump coronary artery bypass grafting (OPCAB) would improve postoperative clinical outcomes or minimize the incidence of postoperative graft failure. In total, 101 papers were found using the reported search, 14 of which represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. One meta-analysis and 3 randomized controlled trials showed that DAPT following OPCAB is associated with decreased incidence of saphenous vein graft occlusion. One randomized controlled trial and 4 observational studies showed no effect of DAPT on mortality following OPCAB, whereas 3 observational studies showed that DAPT decreased mortality. One meta-analysis and 4 observational studies showed that DAPT reduced the incidence of cardiac events following OPCAB. One randomized controlled trial and 4 observational studies showed that DAPT did not increase the incidence of major or minor bleeding complications following OPCAB. The results presented suggest that administration of DAPT in patients following OPCAB for at least 3 months improves saphenous vein graft patency and could be protective against recurrence of cardiac events, especially acute coronary syndrome, in comparison with aspirin monotherapy. The administration of DAPT following OPCAB is safe and is not associated with increased incidence of major or minor bleeding complications when compared with aspirin alone. Dual-antiplatelet therapy , Off-pump coronary artery bypass grafting , Outcomes INTRODUCTION A best evidence topic was constructed according to a structured protocol. This is fully described in the ICVTS [1]. THREE-PART QUESTION Is [dual-antiplatelet therapy] beneficial for patients following [off-pump coronary artery bypass grafting] in terms of [graft failure and clinical outcomes]? CLINICAL SCENARIO You performed an elective off-pump coronary artery bypass grafting (OPCAB) to a 60-year-old man with multi-vessel coronary artery disease and diabetes. You administer aspirin 6-h following surgery and plan to continue this for life. A colleague remarks that OPCAB is related to a significant increase in overall graft occlusion when compared with on-pump coronary artery bypass grafting (CABG) and wonders whether administration of dual-antiplatelet therapy (DAPT) might improve graft patency or clinical outcomes. You resolve to search the literature yourself. SEARCH STRATEGY The literature was reviewed by searching MEDLINE from 1950 to October 2017 using PubMed interface: ((OPCAB OR off-pump OR off-pump OR off-pump OR beating heart)) AND ((DAPT OR dual-antiplatelet therapy) OR ((aspirin) AND (platelet aggregation inhibitors OR clopidogrel OR ticagrelor OR prasugrel))). In addition, similar searches were performed in EMBASE and Cochrane Central Registry of Controlled Trials. SEARCH OUTCOME One hundred and one papers were found using the reported search. From these, 14 papers were identified, which provided the best evidence to answer the clinical question. These are presented in Table 1. Table 1: Best evidence papers Author, date, journal and country Study type (level of evidence) Patient group Outcomes Key results Comments Deo et al. (2013), J Card Surg, USA [2] Meta-analysis (level 1) n = 1275 2 RCTs + 2 observational studies DAPT: aspirin + clopidogrel 75 mg/day n = 688 patients Control: aspirin n = 587 patients Perioperative adverse cardiac events defined as perioperative angina or MI Angiographic outcomes at follow-up Perioperative adverse cardiac events DAPT vs Control RR 0.29, 95% CI 0.11–0.72; P = 0.008 Angiographic outcomes SVG DAPT vs Control RR 0.45; 95% CI 0.21–0.98; P = 0.04 Mannacio et al. (2012), Heart, Italy [3] Randomized controlled trial (level 2a) n = 300 DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 150 patients Control: aspirin 100 mg/day n = 150 patients DAPT continued for 12 months Antiplatelet drugs administered when postoperative chest drainage was < 50 ml/h for 2 consecutive hours Clinical and angiographic outcomes at mean follow-up: 12 months Bleeding complications DAPT was a strong predictor of SVG patency (RR 5.1, 95% CI 1.4–16.3; P < 0.01) Major bleeding DAPT vs Control 1.3% vs 1.3% (P = 1) Minor bleeding DAPT vs Control 2% vs 1.3% (P = 0.5) MI DAPT vs Control 2% vs 4% (P = 0.5) Coronary reintervention DAPT vs Control 0.6% vs 1.3% (P = 0.5) Mortality DAPT vs Control 0.6% vs 1.3% (P = 0.5) Angiographic outcomes (percent of the occluded grafts) LIMA DAPT vs Control 1.4% vs 2.1% (P = 0.5) RIMA DAPT vs Control 0% vs 2.8% (P = 0.5) RA DAPT vs Control 3.5% vs 0% (P = 0.5) SVG DAPT vs Control 7.4% vs 13.1% (P = 0.04) Total occluded grafts DAPT vs Control 15.2% vs 27% (P = 0.02) Gao et al. (2010), J Am Coll Cardiol, China [4] Randomized controlled trial (level 2a) n = 224 patients who underwent on-pump CABG or OPCAB 58.4% of the patients underwent OPCAB DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 113 patients Control: aspirin 100 mg/day n = 111 patients DAPT continued for 3 months Antiplatelet drugs administered when postoperative chest drainage was <30 ml/h for 2 consecutive hours Angiographic outcomes at mean follow-up: 3 months Angiographic outcomes (percent of the occluded grafts) Multivariate analysis showed that DAPT independently increased venous graft patency (RR 1.996, 95% CI 1.015–3.922; P = 0.045) LIMA DAPT vs Control 1.8% vs 0.9% (P = 0.583) RA DAPT vs Control 25% vs 33.3% (P = 0.809) SVG DAPT vs Control 8.4% vs 14.3% (P = 0.043) Total occluded grafts DAPT vs Control 6.5% vs 10.3% (P = 0.07) Mujanovic et al. (2009), Innovations (Phila), Bosnia [5] Randomized controlled trial (level 2a) n = 20 DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 10 patients Control: aspirin 100 mg/day n = 10 patients DAPT continued for 3 months Angiographic outcomes at follow-up: 3 months Angiographic outcomes (percent of the occluded grafts) LIMA DAPT vs Control 0% vs 0% SVG DAPT vs Control 10.52% vs 47.05% (P < 0.05) Total occluded grafts DAPT vs Control 6.89% vs 29.62% (P = 0.037) Wang et al. (2014), J Biomed Res, China [6] Randomized controlled trial (level 2a) n = 60 DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 28 patients Control: aspirin 100 mg/day n = 29 patients Cardiac events defined as: death, MI and heart failure In-hospital cardiac events DAPT vs Control 7.14% vs 10.34% (P > 0.05) Benedetto et al. (2017), Eur J Cardiothorac Surg, UK [7] Observational study (level 2b) n = 1190 DAPT: aspirin + clopidogrel n = 430 Control: aspirin n = 760 MACCE defined as occurrence of cardiovascular death, MI, either ST elevation MI or non-ST-elevation MI, cerebrovascular accident or repeat revascularization Follow-up: 12 months MACCE at follow-up DAPT vs Control HR 0.90, 95% CI 0.50–1.63; P  = 0.73 Cardiovascular death, MI or cerebrovascular accident DAPT vs Control HR 0.53, 95% CI 0.25–1.11; P  = 0.09 Prates et al. (2016), Braz J Cardiovasc Surg, USA [8] Observational study (level 2b) n = 790 DAPT: aspirin + clopidogrel n = 378 Control: aspirin n = 412 Follow-up: 12 months Mortality at 1 year DAPT vs Control 2.6% vs 4.9% (P > 0.05) Ebrahimi et al. (2014), Ann Thorac Surg, USA [9] Observational study (level 2b) n = 489 DAPT: aspirin + clopidogrel (doses not demonstrated) n = 221 patients Control: aspirin (doses not demonstrated) n = 268 patients Angiographic outcome at 1-year follow-up Angiographic outcomes (percent of the occluded grafts) SVG DAPT vs Control 15.5% vs 17.4% (P = 0.56) López et al. (2013), J Card Surg, Spain [10] Observational study (level 2b) n = 237 DAPT: aspirin 100 mg/day +  clopidogrel 75 mg/day n = 109 patients Control: aspirin 100 mg/day n = 128 patients Clinical outcomes at mean follow-up: 23.85 + 0.5 months Bleeding complications Multivariate analysis showed that DAPT was an independent protective factor in the occurrence of cardiac events (HR 0.395, 95% CI 0.176–0.885; P = 0.024) Major bleeding DAPT vs Control 0.9% vs 0.8% (P = 0.909) Minor bleeding DAPT vs Control 3.7% vs 2.3% (P = 0.548) Acute coronary syndrome DAPT vs Control 3.7% vs 10.9% (P = 0.035) Coronary reintervention DAPT vs Control 4.6% vs 5.5% (P = 0.758) Cardiovascular death DAPT vs Control 1.8% vs 4.7% (P = 0.226) Williams et al. (2013), J Thromb Thrombolysis, USA [11] Observational (level 2b) n = 631 DAPT: aspirin + clopidogrel (doses not demonstrated) n = 212 patients Control: aspirin (doses not demonstrated) n = 419 patients Clinical outcomes at follow-up: 5 years Mortality DAPT vs Control HR 0.40, 95% CI 0.2–0.80; P < 0.05 Mortality or MI DAPT vs Control HR 0.53, 95% CI 0.30–0.94; P < 0.05 Mortality, MI or revascularization DAPT vs Control HR 0.75, 95% CI 0.51–1.11; P > 0.05 Kim et al. (2009), J Thorac Cardiovasc Surg, USA [12] Observational study (level 2b) n = 4419 DAPT: aspirin + clopidogrel (doses not demonstrated) n = 1567 patients Control: aspirin (doses not demonstrated) n = 2852 patients Ischaemic or thrombotic events are defined as postoperative acute MI, stroke and venous thromboembolism Any bleeding events defined as post-procedural haemorrhage or haematoma and gastrointestinal haemorrhage Clinical outcomes at follow-up: 30 days Any bleeding events DAPT vs Control 3.64% vs 4.94% (P < 0.05) Any ischaemic or thrombotic events DAPT vs Control 1.21% vs 2.03% (P > 0.05) In-hospital mortality DAPT vs Control 1.08% vs 2.35% (P > 0.05) Gurbuz et al. (2006), Eur J Cardiothorac Surg, Turkey, USA [13] Observational study (level 2b) n = 591 DAPT: aspirin 81 mg/day +  clopidogrel 75 mg/day n = 325 patients Control: aspirin 325 mg/day n = 266 patients DAPT continued for 30 days or longer DAPT administered on the 1st postoperative day Clinical outcomes at mean follow-up: 37.7 + 13.4 months Bleeding complications DAPT independently decreased adverse cardiac events (OR 0.2, 95% CI 0.10–0.45; P < 0.0001) The use of DAPT >30 days following OPCAB did not further improve the outcomes Major bleeding DAPT vs Control 0.6% vs 0.75% (P = 0.8) Minor bleeding DAPT vs Control 1.5% vs 3% Recurrent angina DAPT vs Control 1.8% vs 8.6% (P < 0.0001) MI DAPT vs Control 0% vs 3.4% (P < 0.001) Coronary reintervention DAPT vs Control 0.6% vs 6.8% (P < 0.0001) Mortality DAPT vs Control 2.2% vs 8.3% (P < 0.0001) Halkos et al. (2006), Ann Thorac Surg, USA [14] Observational study (level 2b) n = 364 DAPT: aspirin + 75 mg clopidogrel n = 193 patients Control: aspirin n = 171 patients Clopidogrel administered 4-h after surgery if chest drainage was <100 ml/h DAPT continued for 4 weeks Cardiac events defined as new-onset or unstable angina, ST-elevation or non-ST-elevation MI and coronary reintervention Bleeding complications Major bleeding DAPT vs Control 1.1% vs 0% (P > 0.05) Minor bleeding DAPT vs Control 1.1% vs 0.7% (P > 0.05) Mortality 30 Days DAPT vs Control 1.6% vs 3.5% (P > 0.05) 6 Months DAPT vs Control 3.4% vs 0.6% (P > 0.05) Cardiac events 30 Days DAPT vs Control 0% vs 0.7% (P > 0.05) 6 Months DAPT vs Control 1.7% vs 3.3% (P > 0.05) Cerebrovascular events 30 Days DAPT vs Control 0.6% vs 0% (P > 0.05) 6 Months DAPT vs Control 1.7% vs 2% (P > 0.05) Ibrahim et al. (2006), Heart Surg Forum, Norway [15] Observational study (level 2b) n = 94 DAPT: aspirin 75–160 mg + 75 mg clopidogrel Control: aspirin 75–160 mg DAPT continued for 4 weeks Angiographic outcomes in 62 patients (64%) at follow-up: 185 + 92 days Angiographic outcomes (percent of the occluded grafts) LIMA DAPT vs Control 4% vs 8% (P > 0.5) SVG DAPT vs Control 13% vs 34% (P > 0.5) Total occluded grafts DAPT vs Control 7% vs 16% (P > 0.5) Author, date, journal and country Study type (level of evidence) Patient group Outcomes Key results Comments Deo et al. (2013), J Card Surg, USA [2] Meta-analysis (level 1) n = 1275 2 RCTs + 2 observational studies DAPT: aspirin + clopidogrel 75 mg/day n = 688 patients Control: aspirin n = 587 patients Perioperative adverse cardiac events defined as perioperative angina or MI Angiographic outcomes at follow-up Perioperative adverse cardiac events DAPT vs Control RR 0.29, 95% CI 0.11–0.72; P = 0.008 Angiographic outcomes SVG DAPT vs Control RR 0.45; 95% CI 0.21–0.98; P = 0.04 Mannacio et al. (2012), Heart, Italy [3] Randomized controlled trial (level 2a) n = 300 DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 150 patients Control: aspirin 100 mg/day n = 150 patients DAPT continued for 12 months Antiplatelet drugs administered when postoperative chest drainage was < 50 ml/h for 2 consecutive hours Clinical and angiographic outcomes at mean follow-up: 12 months Bleeding complications DAPT was a strong predictor of SVG patency (RR 5.1, 95% CI 1.4–16.3; P < 0.01) Major bleeding DAPT vs Control 1.3% vs 1.3% (P = 1) Minor bleeding DAPT vs Control 2% vs 1.3% (P = 0.5) MI DAPT vs Control 2% vs 4% (P = 0.5) Coronary reintervention DAPT vs Control 0.6% vs 1.3% (P = 0.5) Mortality DAPT vs Control 0.6% vs 1.3% (P = 0.5) Angiographic outcomes (percent of the occluded grafts) LIMA DAPT vs Control 1.4% vs 2.1% (P = 0.5) RIMA DAPT vs Control 0% vs 2.8% (P = 0.5) RA DAPT vs Control 3.5% vs 0% (P = 0.5) SVG DAPT vs Control 7.4% vs 13.1% (P = 0.04) Total occluded grafts DAPT vs Control 15.2% vs 27% (P = 0.02) Gao et al. (2010), J Am Coll Cardiol, China [4] Randomized controlled trial (level 2a) n = 224 patients who underwent on-pump CABG or OPCAB 58.4% of the patients underwent OPCAB DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 113 patients Control: aspirin 100 mg/day n = 111 patients DAPT continued for 3 months Antiplatelet drugs administered when postoperative chest drainage was <30 ml/h for 2 consecutive hours Angiographic outcomes at mean follow-up: 3 months Angiographic outcomes (percent of the occluded grafts) Multivariate analysis showed that DAPT independently increased venous graft patency (RR 1.996, 95% CI 1.015–3.922; P = 0.045) LIMA DAPT vs Control 1.8% vs 0.9% (P = 0.583) RA DAPT vs Control 25% vs 33.3% (P = 0.809) SVG DAPT vs Control 8.4% vs 14.3% (P = 0.043) Total occluded grafts DAPT vs Control 6.5% vs 10.3% (P = 0.07) Mujanovic et al. (2009), Innovations (Phila), Bosnia [5] Randomized controlled trial (level 2a) n = 20 DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 10 patients Control: aspirin 100 mg/day n = 10 patients DAPT continued for 3 months Angiographic outcomes at follow-up: 3 months Angiographic outcomes (percent of the occluded grafts) LIMA DAPT vs Control 0% vs 0% SVG DAPT vs Control 10.52% vs 47.05% (P < 0.05) Total occluded grafts DAPT vs Control 6.89% vs 29.62% (P = 0.037) Wang et al. (2014), J Biomed Res, China [6] Randomized controlled trial (level 2a) n = 60 DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 28 patients Control: aspirin 100 mg/day n = 29 patients Cardiac events defined as: death, MI and heart failure In-hospital cardiac events DAPT vs Control 7.14% vs 10.34% (P > 0.05) Benedetto et al. (2017), Eur J Cardiothorac Surg, UK [7] Observational study (level 2b) n = 1190 DAPT: aspirin + clopidogrel n = 430 Control: aspirin n = 760 MACCE defined as occurrence of cardiovascular death, MI, either ST elevation MI or non-ST-elevation MI, cerebrovascular accident or repeat revascularization Follow-up: 12 months MACCE at follow-up DAPT vs Control HR 0.90, 95% CI 0.50–1.63; P  = 0.73 Cardiovascular death, MI or cerebrovascular accident DAPT vs Control HR 0.53, 95% CI 0.25–1.11; P  = 0.09 Prates et al. (2016), Braz J Cardiovasc Surg, USA [8] Observational study (level 2b) n = 790 DAPT: aspirin + clopidogrel n = 378 Control: aspirin n = 412 Follow-up: 12 months Mortality at 1 year DAPT vs Control 2.6% vs 4.9% (P > 0.05) Ebrahimi et al. (2014), Ann Thorac Surg, USA [9] Observational study (level 2b) n = 489 DAPT: aspirin + clopidogrel (doses not demonstrated) n = 221 patients Control: aspirin (doses not demonstrated) n = 268 patients Angiographic outcome at 1-year follow-up Angiographic outcomes (percent of the occluded grafts) SVG DAPT vs Control 15.5% vs 17.4% (P = 0.56) López et al. (2013), J Card Surg, Spain [10] Observational study (level 2b) n = 237 DAPT: aspirin 100 mg/day +  clopidogrel 75 mg/day n = 109 patients Control: aspirin 100 mg/day n = 128 patients Clinical outcomes at mean follow-up: 23.85 + 0.5 months Bleeding complications Multivariate analysis showed that DAPT was an independent protective factor in the occurrence of cardiac events (HR 0.395, 95% CI 0.176–0.885; P = 0.024) Major bleeding DAPT vs Control 0.9% vs 0.8% (P = 0.909) Minor bleeding DAPT vs Control 3.7% vs 2.3% (P = 0.548) Acute coronary syndrome DAPT vs Control 3.7% vs 10.9% (P = 0.035) Coronary reintervention DAPT vs Control 4.6% vs 5.5% (P = 0.758) Cardiovascular death DAPT vs Control 1.8% vs 4.7% (P = 0.226) Williams et al. (2013), J Thromb Thrombolysis, USA [11] Observational (level 2b) n = 631 DAPT: aspirin + clopidogrel (doses not demonstrated) n = 212 patients Control: aspirin (doses not demonstrated) n = 419 patients Clinical outcomes at follow-up: 5 years Mortality DAPT vs Control HR 0.40, 95% CI 0.2–0.80; P < 0.05 Mortality or MI DAPT vs Control HR 0.53, 95% CI 0.30–0.94; P < 0.05 Mortality, MI or revascularization DAPT vs Control HR 0.75, 95% CI 0.51–1.11; P > 0.05 Kim et al. (2009), J Thorac Cardiovasc Surg, USA [12] Observational study (level 2b) n = 4419 DAPT: aspirin + clopidogrel (doses not demonstrated) n = 1567 patients Control: aspirin (doses not demonstrated) n = 2852 patients Ischaemic or thrombotic events are defined as postoperative acute MI, stroke and venous thromboembolism Any bleeding events defined as post-procedural haemorrhage or haematoma and gastrointestinal haemorrhage Clinical outcomes at follow-up: 30 days Any bleeding events DAPT vs Control 3.64% vs 4.94% (P < 0.05) Any ischaemic or thrombotic events DAPT vs Control 1.21% vs 2.03% (P > 0.05) In-hospital mortality DAPT vs Control 1.08% vs 2.35% (P > 0.05) Gurbuz et al. (2006), Eur J Cardiothorac Surg, Turkey, USA [13] Observational study (level 2b) n = 591 DAPT: aspirin 81 mg/day +  clopidogrel 75 mg/day n = 325 patients Control: aspirin 325 mg/day n = 266 patients DAPT continued for 30 days or longer DAPT administered on the 1st postoperative day Clinical outcomes at mean follow-up: 37.7 + 13.4 months Bleeding complications DAPT independently decreased adverse cardiac events (OR 0.2, 95% CI 0.10–0.45; P < 0.0001) The use of DAPT >30 days following OPCAB did not further improve the outcomes Major bleeding DAPT vs Control 0.6% vs 0.75% (P = 0.8) Minor bleeding DAPT vs Control 1.5% vs 3% Recurrent angina DAPT vs Control 1.8% vs 8.6% (P < 0.0001) MI DAPT vs Control 0% vs 3.4% (P < 0.001) Coronary reintervention DAPT vs Control 0.6% vs 6.8% (P < 0.0001) Mortality DAPT vs Control 2.2% vs 8.3% (P < 0.0001) Halkos et al. (2006), Ann Thorac Surg, USA [14] Observational study (level 2b) n = 364 DAPT: aspirin + 75 mg clopidogrel n = 193 patients Control: aspirin n = 171 patients Clopidogrel administered 4-h after surgery if chest drainage was <100 ml/h DAPT continued for 4 weeks Cardiac events defined as new-onset or unstable angina, ST-elevation or non-ST-elevation MI and coronary reintervention Bleeding complications Major bleeding DAPT vs Control 1.1% vs 0% (P > 0.05) Minor bleeding DAPT vs Control 1.1% vs 0.7% (P > 0.05) Mortality 30 Days DAPT vs Control 1.6% vs 3.5% (P > 0.05) 6 Months DAPT vs Control 3.4% vs 0.6% (P > 0.05) Cardiac events 30 Days DAPT vs Control 0% vs 0.7% (P > 0.05) 6 Months DAPT vs Control 1.7% vs 3.3% (P > 0.05) Cerebrovascular events 30 Days DAPT vs Control 0.6% vs 0% (P > 0.05) 6 Months DAPT vs Control 1.7% vs 2% (P > 0.05) Ibrahim et al. (2006), Heart Surg Forum, Norway [15] Observational study (level 2b) n = 94 DAPT: aspirin 75–160 mg + 75 mg clopidogrel Control: aspirin 75–160 mg DAPT continued for 4 weeks Angiographic outcomes in 62 patients (64%) at follow-up: 185 + 92 days Angiographic outcomes (percent of the occluded grafts) LIMA DAPT vs Control 4% vs 8% (P > 0.5) SVG DAPT vs Control 13% vs 34% (P > 0.5) Total occluded grafts DAPT vs Control 7% vs 16% (P > 0.5) CABG: coronary artery bypass grafting; CI: confidence interval; DAPT: dual-antiplatelet therapy; HR: hazard ratio; LIMA: left internal mammary artery; MI: myocardial infarction; OPCAB: off-pump coronary artery bypass grafting; OR: odds ratio; RA: radial artery; RCT: randomized controlled trial; RIMA: right internal mammary artery; RR: relative risk; SVG: saphenous vein graft. Table 1: Best evidence papers Author, date, journal and country Study type (level of evidence) Patient group Outcomes Key results Comments Deo et al. (2013), J Card Surg, USA [2] Meta-analysis (level 1) n = 1275 2 RCTs + 2 observational studies DAPT: aspirin + clopidogrel 75 mg/day n = 688 patients Control: aspirin n = 587 patients Perioperative adverse cardiac events defined as perioperative angina or MI Angiographic outcomes at follow-up Perioperative adverse cardiac events DAPT vs Control RR 0.29, 95% CI 0.11–0.72; P = 0.008 Angiographic outcomes SVG DAPT vs Control RR 0.45; 95% CI 0.21–0.98; P = 0.04 Mannacio et al. (2012), Heart, Italy [3] Randomized controlled trial (level 2a) n = 300 DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 150 patients Control: aspirin 100 mg/day n = 150 patients DAPT continued for 12 months Antiplatelet drugs administered when postoperative chest drainage was < 50 ml/h for 2 consecutive hours Clinical and angiographic outcomes at mean follow-up: 12 months Bleeding complications DAPT was a strong predictor of SVG patency (RR 5.1, 95% CI 1.4–16.3; P < 0.01) Major bleeding DAPT vs Control 1.3% vs 1.3% (P = 1) Minor bleeding DAPT vs Control 2% vs 1.3% (P = 0.5) MI DAPT vs Control 2% vs 4% (P = 0.5) Coronary reintervention DAPT vs Control 0.6% vs 1.3% (P = 0.5) Mortality DAPT vs Control 0.6% vs 1.3% (P = 0.5) Angiographic outcomes (percent of the occluded grafts) LIMA DAPT vs Control 1.4% vs 2.1% (P = 0.5) RIMA DAPT vs Control 0% vs 2.8% (P = 0.5) RA DAPT vs Control 3.5% vs 0% (P = 0.5) SVG DAPT vs Control 7.4% vs 13.1% (P = 0.04) Total occluded grafts DAPT vs Control 15.2% vs 27% (P = 0.02) Gao et al. (2010), J Am Coll Cardiol, China [4] Randomized controlled trial (level 2a) n = 224 patients who underwent on-pump CABG or OPCAB 58.4% of the patients underwent OPCAB DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 113 patients Control: aspirin 100 mg/day n = 111 patients DAPT continued for 3 months Antiplatelet drugs administered when postoperative chest drainage was <30 ml/h for 2 consecutive hours Angiographic outcomes at mean follow-up: 3 months Angiographic outcomes (percent of the occluded grafts) Multivariate analysis showed that DAPT independently increased venous graft patency (RR 1.996, 95% CI 1.015–3.922; P = 0.045) LIMA DAPT vs Control 1.8% vs 0.9% (P = 0.583) RA DAPT vs Control 25% vs 33.3% (P = 0.809) SVG DAPT vs Control 8.4% vs 14.3% (P = 0.043) Total occluded grafts DAPT vs Control 6.5% vs 10.3% (P = 0.07) Mujanovic et al. (2009), Innovations (Phila), Bosnia [5] Randomized controlled trial (level 2a) n = 20 DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 10 patients Control: aspirin 100 mg/day n = 10 patients DAPT continued for 3 months Angiographic outcomes at follow-up: 3 months Angiographic outcomes (percent of the occluded grafts) LIMA DAPT vs Control 0% vs 0% SVG DAPT vs Control 10.52% vs 47.05% (P < 0.05) Total occluded grafts DAPT vs Control 6.89% vs 29.62% (P = 0.037) Wang et al. (2014), J Biomed Res, China [6] Randomized controlled trial (level 2a) n = 60 DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 28 patients Control: aspirin 100 mg/day n = 29 patients Cardiac events defined as: death, MI and heart failure In-hospital cardiac events DAPT vs Control 7.14% vs 10.34% (P > 0.05) Benedetto et al. (2017), Eur J Cardiothorac Surg, UK [7] Observational study (level 2b) n = 1190 DAPT: aspirin + clopidogrel n = 430 Control: aspirin n = 760 MACCE defined as occurrence of cardiovascular death, MI, either ST elevation MI or non-ST-elevation MI, cerebrovascular accident or repeat revascularization Follow-up: 12 months MACCE at follow-up DAPT vs Control HR 0.90, 95% CI 0.50–1.63; P  = 0.73 Cardiovascular death, MI or cerebrovascular accident DAPT vs Control HR 0.53, 95% CI 0.25–1.11; P  = 0.09 Prates et al. (2016), Braz J Cardiovasc Surg, USA [8] Observational study (level 2b) n = 790 DAPT: aspirin + clopidogrel n = 378 Control: aspirin n = 412 Follow-up: 12 months Mortality at 1 year DAPT vs Control 2.6% vs 4.9% (P > 0.05) Ebrahimi et al. (2014), Ann Thorac Surg, USA [9] Observational study (level 2b) n = 489 DAPT: aspirin + clopidogrel (doses not demonstrated) n = 221 patients Control: aspirin (doses not demonstrated) n = 268 patients Angiographic outcome at 1-year follow-up Angiographic outcomes (percent of the occluded grafts) SVG DAPT vs Control 15.5% vs 17.4% (P = 0.56) López et al. (2013), J Card Surg, Spain [10] Observational study (level 2b) n = 237 DAPT: aspirin 100 mg/day +  clopidogrel 75 mg/day n = 109 patients Control: aspirin 100 mg/day n = 128 patients Clinical outcomes at mean follow-up: 23.85 + 0.5 months Bleeding complications Multivariate analysis showed that DAPT was an independent protective factor in the occurrence of cardiac events (HR 0.395, 95% CI 0.176–0.885; P = 0.024) Major bleeding DAPT vs Control 0.9% vs 0.8% (P = 0.909) Minor bleeding DAPT vs Control 3.7% vs 2.3% (P = 0.548) Acute coronary syndrome DAPT vs Control 3.7% vs 10.9% (P = 0.035) Coronary reintervention DAPT vs Control 4.6% vs 5.5% (P = 0.758) Cardiovascular death DAPT vs Control 1.8% vs 4.7% (P = 0.226) Williams et al. (2013), J Thromb Thrombolysis, USA [11] Observational (level 2b) n = 631 DAPT: aspirin + clopidogrel (doses not demonstrated) n = 212 patients Control: aspirin (doses not demonstrated) n = 419 patients Clinical outcomes at follow-up: 5 years Mortality DAPT vs Control HR 0.40, 95% CI 0.2–0.80; P < 0.05 Mortality or MI DAPT vs Control HR 0.53, 95% CI 0.30–0.94; P < 0.05 Mortality, MI or revascularization DAPT vs Control HR 0.75, 95% CI 0.51–1.11; P > 0.05 Kim et al. (2009), J Thorac Cardiovasc Surg, USA [12] Observational study (level 2b) n = 4419 DAPT: aspirin + clopidogrel (doses not demonstrated) n = 1567 patients Control: aspirin (doses not demonstrated) n = 2852 patients Ischaemic or thrombotic events are defined as postoperative acute MI, stroke and venous thromboembolism Any bleeding events defined as post-procedural haemorrhage or haematoma and gastrointestinal haemorrhage Clinical outcomes at follow-up: 30 days Any bleeding events DAPT vs Control 3.64% vs 4.94% (P < 0.05) Any ischaemic or thrombotic events DAPT vs Control 1.21% vs 2.03% (P > 0.05) In-hospital mortality DAPT vs Control 1.08% vs 2.35% (P > 0.05) Gurbuz et al. (2006), Eur J Cardiothorac Surg, Turkey, USA [13] Observational study (level 2b) n = 591 DAPT: aspirin 81 mg/day +  clopidogrel 75 mg/day n = 325 patients Control: aspirin 325 mg/day n = 266 patients DAPT continued for 30 days or longer DAPT administered on the 1st postoperative day Clinical outcomes at mean follow-up: 37.7 + 13.4 months Bleeding complications DAPT independently decreased adverse cardiac events (OR 0.2, 95% CI 0.10–0.45; P < 0.0001) The use of DAPT >30 days following OPCAB did not further improve the outcomes Major bleeding DAPT vs Control 0.6% vs 0.75% (P = 0.8) Minor bleeding DAPT vs Control 1.5% vs 3% Recurrent angina DAPT vs Control 1.8% vs 8.6% (P < 0.0001) MI DAPT vs Control 0% vs 3.4% (P < 0.001) Coronary reintervention DAPT vs Control 0.6% vs 6.8% (P < 0.0001) Mortality DAPT vs Control 2.2% vs 8.3% (P < 0.0001) Halkos et al. (2006), Ann Thorac Surg, USA [14] Observational study (level 2b) n = 364 DAPT: aspirin + 75 mg clopidogrel n = 193 patients Control: aspirin n = 171 patients Clopidogrel administered 4-h after surgery if chest drainage was <100 ml/h DAPT continued for 4 weeks Cardiac events defined as new-onset or unstable angina, ST-elevation or non-ST-elevation MI and coronary reintervention Bleeding complications Major bleeding DAPT vs Control 1.1% vs 0% (P > 0.05) Minor bleeding DAPT vs Control 1.1% vs 0.7% (P > 0.05) Mortality 30 Days DAPT vs Control 1.6% vs 3.5% (P > 0.05) 6 Months DAPT vs Control 3.4% vs 0.6% (P > 0.05) Cardiac events 30 Days DAPT vs Control 0% vs 0.7% (P > 0.05) 6 Months DAPT vs Control 1.7% vs 3.3% (P > 0.05) Cerebrovascular events 30 Days DAPT vs Control 0.6% vs 0% (P > 0.05) 6 Months DAPT vs Control 1.7% vs 2% (P > 0.05) Ibrahim et al. (2006), Heart Surg Forum, Norway [15] Observational study (level 2b) n = 94 DAPT: aspirin 75–160 mg + 75 mg clopidogrel Control: aspirin 75–160 mg DAPT continued for 4 weeks Angiographic outcomes in 62 patients (64%) at follow-up: 185 + 92 days Angiographic outcomes (percent of the occluded grafts) LIMA DAPT vs Control 4% vs 8% (P > 0.5) SVG DAPT vs Control 13% vs 34% (P > 0.5) Total occluded grafts DAPT vs Control 7% vs 16% (P > 0.5) Author, date, journal and country Study type (level of evidence) Patient group Outcomes Key results Comments Deo et al. (2013), J Card Surg, USA [2] Meta-analysis (level 1) n = 1275 2 RCTs + 2 observational studies DAPT: aspirin + clopidogrel 75 mg/day n = 688 patients Control: aspirin n = 587 patients Perioperative adverse cardiac events defined as perioperative angina or MI Angiographic outcomes at follow-up Perioperative adverse cardiac events DAPT vs Control RR 0.29, 95% CI 0.11–0.72; P = 0.008 Angiographic outcomes SVG DAPT vs Control RR 0.45; 95% CI 0.21–0.98; P = 0.04 Mannacio et al. (2012), Heart, Italy [3] Randomized controlled trial (level 2a) n = 300 DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 150 patients Control: aspirin 100 mg/day n = 150 patients DAPT continued for 12 months Antiplatelet drugs administered when postoperative chest drainage was < 50 ml/h for 2 consecutive hours Clinical and angiographic outcomes at mean follow-up: 12 months Bleeding complications DAPT was a strong predictor of SVG patency (RR 5.1, 95% CI 1.4–16.3; P < 0.01) Major bleeding DAPT vs Control 1.3% vs 1.3% (P = 1) Minor bleeding DAPT vs Control 2% vs 1.3% (P = 0.5) MI DAPT vs Control 2% vs 4% (P = 0.5) Coronary reintervention DAPT vs Control 0.6% vs 1.3% (P = 0.5) Mortality DAPT vs Control 0.6% vs 1.3% (P = 0.5) Angiographic outcomes (percent of the occluded grafts) LIMA DAPT vs Control 1.4% vs 2.1% (P = 0.5) RIMA DAPT vs Control 0% vs 2.8% (P = 0.5) RA DAPT vs Control 3.5% vs 0% (P = 0.5) SVG DAPT vs Control 7.4% vs 13.1% (P = 0.04) Total occluded grafts DAPT vs Control 15.2% vs 27% (P = 0.02) Gao et al. (2010), J Am Coll Cardiol, China [4] Randomized controlled trial (level 2a) n = 224 patients who underwent on-pump CABG or OPCAB 58.4% of the patients underwent OPCAB DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 113 patients Control: aspirin 100 mg/day n = 111 patients DAPT continued for 3 months Antiplatelet drugs administered when postoperative chest drainage was <30 ml/h for 2 consecutive hours Angiographic outcomes at mean follow-up: 3 months Angiographic outcomes (percent of the occluded grafts) Multivariate analysis showed that DAPT independently increased venous graft patency (RR 1.996, 95% CI 1.015–3.922; P = 0.045) LIMA DAPT vs Control 1.8% vs 0.9% (P = 0.583) RA DAPT vs Control 25% vs 33.3% (P = 0.809) SVG DAPT vs Control 8.4% vs 14.3% (P = 0.043) Total occluded grafts DAPT vs Control 6.5% vs 10.3% (P = 0.07) Mujanovic et al. (2009), Innovations (Phila), Bosnia [5] Randomized controlled trial (level 2a) n = 20 DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 10 patients Control: aspirin 100 mg/day n = 10 patients DAPT continued for 3 months Angiographic outcomes at follow-up: 3 months Angiographic outcomes (percent of the occluded grafts) LIMA DAPT vs Control 0% vs 0% SVG DAPT vs Control 10.52% vs 47.05% (P < 0.05) Total occluded grafts DAPT vs Control 6.89% vs 29.62% (P = 0.037) Wang et al. (2014), J Biomed Res, China [6] Randomized controlled trial (level 2a) n = 60 DAPT: aspirin 100 mg/day + clopidogrel 75 mg/day n = 28 patients Control: aspirin 100 mg/day n = 29 patients Cardiac events defined as: death, MI and heart failure In-hospital cardiac events DAPT vs Control 7.14% vs 10.34% (P > 0.05) Benedetto et al. (2017), Eur J Cardiothorac Surg, UK [7] Observational study (level 2b) n = 1190 DAPT: aspirin + clopidogrel n = 430 Control: aspirin n = 760 MACCE defined as occurrence of cardiovascular death, MI, either ST elevation MI or non-ST-elevation MI, cerebrovascular accident or repeat revascularization Follow-up: 12 months MACCE at follow-up DAPT vs Control HR 0.90, 95% CI 0.50–1.63; P  = 0.73 Cardiovascular death, MI or cerebrovascular accident DAPT vs Control HR 0.53, 95% CI 0.25–1.11; P  = 0.09 Prates et al. (2016), Braz J Cardiovasc Surg, USA [8] Observational study (level 2b) n = 790 DAPT: aspirin + clopidogrel n = 378 Control: aspirin n = 412 Follow-up: 12 months Mortality at 1 year DAPT vs Control 2.6% vs 4.9% (P > 0.05) Ebrahimi et al. (2014), Ann Thorac Surg, USA [9] Observational study (level 2b) n = 489 DAPT: aspirin + clopidogrel (doses not demonstrated) n = 221 patients Control: aspirin (doses not demonstrated) n = 268 patients Angiographic outcome at 1-year follow-up Angiographic outcomes (percent of the occluded grafts) SVG DAPT vs Control 15.5% vs 17.4% (P = 0.56) López et al. (2013), J Card Surg, Spain [10] Observational study (level 2b) n = 237 DAPT: aspirin 100 mg/day +  clopidogrel 75 mg/day n = 109 patients Control: aspirin 100 mg/day n = 128 patients Clinical outcomes at mean follow-up: 23.85 + 0.5 months Bleeding complications Multivariate analysis showed that DAPT was an independent protective factor in the occurrence of cardiac events (HR 0.395, 95% CI 0.176–0.885; P = 0.024) Major bleeding DAPT vs Control 0.9% vs 0.8% (P = 0.909) Minor bleeding DAPT vs Control 3.7% vs 2.3% (P = 0.548) Acute coronary syndrome DAPT vs Control 3.7% vs 10.9% (P = 0.035) Coronary reintervention DAPT vs Control 4.6% vs 5.5% (P = 0.758) Cardiovascular death DAPT vs Control 1.8% vs 4.7% (P = 0.226) Williams et al. (2013), J Thromb Thrombolysis, USA [11] Observational (level 2b) n = 631 DAPT: aspirin + clopidogrel (doses not demonstrated) n = 212 patients Control: aspirin (doses not demonstrated) n = 419 patients Clinical outcomes at follow-up: 5 years Mortality DAPT vs Control HR 0.40, 95% CI 0.2–0.80; P < 0.05 Mortality or MI DAPT vs Control HR 0.53, 95% CI 0.30–0.94; P < 0.05 Mortality, MI or revascularization DAPT vs Control HR 0.75, 95% CI 0.51–1.11; P > 0.05 Kim et al. (2009), J Thorac Cardiovasc Surg, USA [12] Observational study (level 2b) n = 4419 DAPT: aspirin + clopidogrel (doses not demonstrated) n = 1567 patients Control: aspirin (doses not demonstrated) n = 2852 patients Ischaemic or thrombotic events are defined as postoperative acute MI, stroke and venous thromboembolism Any bleeding events defined as post-procedural haemorrhage or haematoma and gastrointestinal haemorrhage Clinical outcomes at follow-up: 30 days Any bleeding events DAPT vs Control 3.64% vs 4.94% (P < 0.05) Any ischaemic or thrombotic events DAPT vs Control 1.21% vs 2.03% (P > 0.05) In-hospital mortality DAPT vs Control 1.08% vs 2.35% (P > 0.05) Gurbuz et al. (2006), Eur J Cardiothorac Surg, Turkey, USA [13] Observational study (level 2b) n = 591 DAPT: aspirin 81 mg/day +  clopidogrel 75 mg/day n = 325 patients Control: aspirin 325 mg/day n = 266 patients DAPT continued for 30 days or longer DAPT administered on the 1st postoperative day Clinical outcomes at mean follow-up: 37.7 + 13.4 months Bleeding complications DAPT independently decreased adverse cardiac events (OR 0.2, 95% CI 0.10–0.45; P < 0.0001) The use of DAPT >30 days following OPCAB did not further improve the outcomes Major bleeding DAPT vs Control 0.6% vs 0.75% (P = 0.8) Minor bleeding DAPT vs Control 1.5% vs 3% Recurrent angina DAPT vs Control 1.8% vs 8.6% (P < 0.0001) MI DAPT vs Control 0% vs 3.4% (P < 0.001) Coronary reintervention DAPT vs Control 0.6% vs 6.8% (P < 0.0001) Mortality DAPT vs Control 2.2% vs 8.3% (P < 0.0001) Halkos et al. (2006), Ann Thorac Surg, USA [14] Observational study (level 2b) n = 364 DAPT: aspirin + 75 mg clopidogrel n = 193 patients Control: aspirin n = 171 patients Clopidogrel administered 4-h after surgery if chest drainage was <100 ml/h DAPT continued for 4 weeks Cardiac events defined as new-onset or unstable angina, ST-elevation or non-ST-elevation MI and coronary reintervention Bleeding complications Major bleeding DAPT vs Control 1.1% vs 0% (P > 0.05) Minor bleeding DAPT vs Control 1.1% vs 0.7% (P > 0.05) Mortality 30 Days DAPT vs Control 1.6% vs 3.5% (P > 0.05) 6 Months DAPT vs Control 3.4% vs 0.6% (P > 0.05) Cardiac events 30 Days DAPT vs Control 0% vs 0.7% (P > 0.05) 6 Months DAPT vs Control 1.7% vs 3.3% (P > 0.05) Cerebrovascular events 30 Days DAPT vs Control 0.6% vs 0% (P > 0.05) 6 Months DAPT vs Control 1.7% vs 2% (P > 0.05) Ibrahim et al. (2006), Heart Surg Forum, Norway [15] Observational study (level 2b) n = 94 DAPT: aspirin 75–160 mg + 75 mg clopidogrel Control: aspirin 75–160 mg DAPT continued for 4 weeks Angiographic outcomes in 62 patients (64%) at follow-up: 185 + 92 days Angiographic outcomes (percent of the occluded grafts) LIMA DAPT vs Control 4% vs 8% (P > 0.5) SVG DAPT vs Control 13% vs 34% (P > 0.5) Total occluded grafts DAPT vs Control 7% vs 16% (P > 0.5) CABG: coronary artery bypass grafting; CI: confidence interval; DAPT: dual-antiplatelet therapy; HR: hazard ratio; LIMA: left internal mammary artery; MI: myocardial infarction; OPCAB: off-pump coronary artery bypass grafting; OR: odds ratio; RA: radial artery; RCT: randomized controlled trial; RIMA: right internal mammary artery; RR: relative risk; SVG: saphenous vein graft. RESULTS Deo et al. [2] in a meta-analysis that included 2 randomized controlled trials (RCTs) and 2 observational studies showed that administration of DAPT following OPCAB is associated with reduced risk of perioperative adverse cardiac events by 71% [relative risk (RR) 0.29, 95% confidence interval (CI) 0.11–0.72; P = 0.008]. Pooled analysis of RCTs revealed that administration of DAPT following OPCAB reduced the incidence of saphenous vein graft (SVG) occlusion by 55% (RR 0.45, 95% CI 0.21–0.98; P = 0.04). Mannacio et al. [3] in a prospective, randomized, placebo-controlled trial showed that administration of DAPT for 12 months in patients following OPCAB is associated with a significant reduction in SVG occlusion in the 1st postoperative year (7.4% vs 13.1%, P = 0.04). They also showed that DAPT was a strong predictor of SVG patency (RR 5.1, 95% CI 1.4–16.3; P < 0.01). Neither benefit nor harm of DAPT on mortality (P = 0.5), myocardial infarction (MI) (P = 0.5) or coronary reintervention (P = 0.5) was observed during the follow-up period. The authors also showed that DAPT was not associated with increased incidence of major (P = 1) or minor (P = 0.5) bleeding complications. Gao et al. [4] in a prospective RCT demonstrated that administration of DAPT for 3 months is associated with reduced incidence of SVG occlusion (8.4% vs 14.3%, P = 0.043). Multivariate analysis showed that DAPT independently increased venous graft patency (RR 1.996, 95% CI 1.015–3.922; P = 0.045). However, this group was a mixture of OPCAB (58%) and on-pump CABG. Mujanovic et al. [5] in a randomized trial showed that DAPT following OPCAB for 3 months is associated with a significant reduction in overall graft occlusion (6.89% vs 29.62%, P = 0.037). The magnitude of reduction was predominantly observed in the rate of SVG occlusion, where DAPT was associated with high reduction in SVG occlusion (10.52% vs 47.05, P < 0.05). Wang et al. [6] in a randomized trial showed no demonstrable effect of DAPT on in-hospital cardiac events in patients following OPCAB (P > 0.05). Benedetto et al. [7] in an observational analysis of patients from the Arterial Revascularization Trial (ART) showed that DAPT following OPCAB did not reduce significantly the risk of major adverse cardiovascular and cerebral events at follow-up [hazard ratio (HR) 0.90, 95% CI 0.50–1.63; P = 0.73] nor did it significantly reduce the risk for the composite of cardiovascular death, MI and cerebrovascular accidents (HR 0.53, 95% CI 0.25–1.11; P = 0.09). Prates et al. [8] in an observational study demonstrated neither benefit nor harm from DAPT as far as 1-year mortality in patients following OPCAB (P > 0.05). Ebrahimi et al. [9] in an observational analysis of patients from the ROOBY trial showed that DAPT did not significantly reduce the incidence of SVG occlusion following OPCAB at 1-year angiographic follow-up (15.5% vs 17.4%, P = 0.56). López et al. [10] in an observational trial observed that DAPT following OPCAB is not associated with increased incidence of major or minor bleeding complications (P = 0.909 and P = 0.548, respectively). They also revealed no difference in terms of coronary reintervention or cardiovascular death. However, they demonstrated that DAPT is associated with decreased incidence of acute coronary syndrome following OPCAB (3.7% vs 10.9%, P = 0.035). They also showed that DAPT was an independent protective factor in the occurrence of cardiac events (HR 0.395; 95% CI 0.176–0.885; P = 0.024). Williams et al. [11] in an observational analysis of patients from the PREVENT IV trial showed that DAPT following OPCAB is associated with reduced long-term hazard of mortality (HR 0.40; 95% CI 0.2–0.80; P < 0.05) and combined MI or mortality (HR 0.53; 95% CI 0.30–0.94; P < 0.05) but not combined MI, mortality and repeated revascularization (HR 0.75; 95% CI 0.51–1.11; P > 0.05). Kim et al. [12] in an observational study showed that DAPT following OPCAB is associated with a non-significant decrease in any ischaemic or thrombotic events (1.21% vs 2.03%, P > 0.05) and in-hospital mortality (1.08% vs 2.35%, P > 0.05) but was associated with a significantly lower incidence of bleeding events when compared with aspirin monotherapy (3.64% vs 4.94%, P < 0.05). Gurbuz et al. [13] in an observational analysis revealed that DAPT following OPCAB for at least 1 month is associated with decreased incidence of recurrent angina (P < 0.0001), MI (P < 0.001), coronary reintervention (P < 0.0001) and reduced mortality (P < 0.0001). They also showed that DAPT independently decreased adverse cardiac events by 80% (OR 0.2; 95% CI 0.10–0.45; P < 0.0001). There was no demonstrable increased incidence of major or minor bleeding complications (P = 0.8) associated with administration of DAPT in this study. Halkos et al. [14] in an observational study showed that administration of DAPT for 1 month following OPCAB is not associated with increased incidence of major (P > 0.05) or minor (P > 0.05) bleeding complications. On the other hand, neither benefit nor harm was observed in terms of mortality, cardiac or cerebrovascular events (P > 0.05). Ibrahim et al. [15] in an observational study investigated the effect of continuation of DAPT for 1 month in patients following OPCAB in terms of angiographic results. At a mean follow-up of 6 ± 3 months, there was a non-significant reduction in graft occlusion when compared with aspirin alone (7% vs 16%), which was more pronounced (yet still not significant) in terms of SVG occlusion (13% vs 34%). CLINICAL BOTTOM LINE Administration of DAPT in patients following OPCAB for at least 3 months improves SVG patency and could be protective against recurrence of cardiac events, especially acute coronary syndrome, in comparison with aspirin monotherapy. Administration of DAPT following OPCAB is safe and is not associated with increased incidence of major or minor bleeding complications when compared with aspirin alone. Conflict of interest: none declared. REFERENCES 1 Dunning J , Prendergast B , Mackway-Jones K. Towards evidence-based medicine in cardiothoracic surgery: best BETS . 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Google Scholar CrossRef Search ADS PubMed 5 Mujanovic E , Nurkic M , Caluk J , Terzic I , Kabil E , Bergsland J. The effect of combined clopidogrel and aspirin therapy after off-pump coronary surgery: a pilot study . Innovations (Phila) 2009 ; 4 : 265 – 8 . Google Scholar CrossRef Search ADS PubMed 6 Wang X , Gong X , Zhu T , Zhang Q , Zhang Y , Wang X et al. Clopidogrel improves aspirin response after off-pump coronary artery bypass surgery . J Biomed Res 2014 ; 28 : 108 – 13 . Google Scholar PubMed 7 Benedetto U , Altman DG , Gerry S , Gray A , Lees B , Flather M et al. ART Investigators . Impact of dual antiplatelet therapy after coronary artery bypass surgery on 1-year outcomes in the Arterial Revascularization Trial . Eur J Cardiothorac Surg 2017 ; 52 : 456 – 61 . Google Scholar PubMed 8 Prates PR , Williams JB , Mehta RH , Stevens SR , Thomas L , Smith PK et al. Clopidogrel use after myocardial revascularization: prevalence, predictors, and one-year survival rate . Braz J Cardiovasc Surg 2016 ; 31 : 106 – 14 . Google Scholar PubMed 9 Ebrahimi R , Bakaeen FG , Uberoi A , Ardehali A , Baltz JH , Hattler B et al. Effect of clopidogrel use post coronary artery bypass surgery on graft patency . Ann Thorac Surg 2014 ; 97 : 15 – 21 . Google Scholar CrossRef Search ADS PubMed 10 López J , Morales C , Avanzas P , Callejo F , Hernández-Vaquero D , Llosa JC. Long-term effect of dual antiplatelet treatment after off-pump coronary artery bypass grafting . J Card Surg 2013 ; 28 : 366 – 72 . Google Scholar CrossRef Search ADS PubMed 11 Williams JB , Lopes RD , Hafley GE , Ferguson TB Jr , Mack MJ , Gibson CM et al. Relationship between postoperative clopidogrel use and subsequent angiographic and clinical outcomes following coronary artery bypass grafting . J Thromb Thrombolysis 2013 ; 36 : 384 – 93 . Google Scholar CrossRef Search ADS PubMed 12 Kim DH , Daskalakis C , Silvestry SC , Sheth MP , Lee AN , Adams S et al. Aspirin and clopidogrel use in the early postoperative period following on-pump and off-pump coronary artery bypass grafting . J Thorac Cardiovasc Surg 2009 ; 138 : 1377 – 84 . Google Scholar CrossRef Search ADS PubMed 13 Gurbuz AT , Zia AA , Vuran AC , Cui H , Aytac A. Postoperative clopidogrel improves mid-term outcome after off-pump coronary artery bypass graft surgery: a prospective study . Eur J Cardiothorac Surg 2006 ; 29 : 190 – 5 . Google Scholar CrossRef Search ADS PubMed 14 Halkos ME , Cooper WA , Petersen R , Puskas JD , Lattouf OM , Craver JM et al. Early administration of clopidogrel is safe after off-pump coronary artery bypass surgery . Ann Thorac Surg 2006 ; 81 : 815 – 9 . Google Scholar CrossRef Search ADS PubMed 15 Ibrahim K , Tjomsland O , Halvorsen D , Wiseth R , Wahba A , Karevold A et al. Effect of clopidogrel on midterm graft patency following off-pump coronary revascularization surgery . Heart Surg Forum 2006 ; 9 : E581 – 856 . Google Scholar CrossRef Search ADS PubMed © The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

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Interactive CardioVascular and Thoracic SurgeryOxford University Press

Published: Apr 5, 2018

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