Ticagrelor versus aspirin and vein graft patency after coronary bypass: A randomized trial.

BACKGROUND: Antiplatelet therapy prevents saphenous vein graft (SVG) occlusion and improves outcomes after coronary artery bypass graft surgery (CABG). However, the optimal postoperative antiplatelet regimen remains unclear. The goal of the Ticagrelor Antiplatelet Therapy to Reduce Graft Events and Thrombosis (TARGET) trial was to assess whether early postoperative ticagrelor reduces SVG occlusion compared to conventional aspirin therapy. METHODS: In this multi-center double-blind randomized trial, 250 patients who had CABG with SVG were randomized to receive either aspirin 81 mg twice daily or ticagrelor 90 mg twice daily. The primary outcome was SVG occlusion at 1 year. RESULTS: Altogether, 123 patients were randomized to aspirin and 127 received ticagrelor. One-year graft assessment was performed in 202 patients (80.8%), examining 588 grafts, yielding an overall graft occlusion rate of 10.9%. The primary outcome, SVG occlusion at 1 year, did not significantly differ between the two groups (17.4% vs. 13.2%, aspirin vs. ticagrelor, p = .30). The incidence of vein grafts with any disease (stenosis or occlusion) did not significantly differ between the groups (21.5% vs. 22.3%, aspirin vs. ticagrelor, p = .90), and the number of patients with vein graft disease did not significantly differ between the groups (29.4% vs. 28.0%, aspirin vs. ticagrelor, p = .88). Freedom from major adverse cardiovascular events at 1 year was similar between the groups (p = .60). CONCLUSIONS: Compared to conventional aspirin therapy, ticagrelor did not significantly reduce vein graft occlusion 1 year after CABG. Further study will assess the impact of ticagrelor on 2-year graft patency for this cohort.

Ticagrelor versus aspirin 2 years after coronary bypass: Observational analysis from the TARGET trial.

BACKGROUND: Compared to conventional aspirin therapy, ticagrelor did not improve vein graft patency 1 year after coronary bypass surgery (CABG) in the ticagrelor antiplatelet therapy to reduce graft events and thrombosis (TARGET) trial. However, it is unknown whether ticagrelor may impact graft patency long-term following surgery. METHODS: In the TARGET multicenter trial, 250 CABG patients were randomized to aspirin 81 mg or ticagrelor 90 mg twice daily. In this observational analysis, 2 years after surgery, vein graft occlusion and clinical events were compared among subjects who agreed to a second year of double-blind study drug administration (N = 156). RESULTS: Two-year graft assessment was performed for 142 patients (80 aspirin patients, 62 ticagrelor patients, 425 total grafts), with an overall 2-year graft occlusion rate of 10.6%. Vein graft occlusion at 2 years, the primary outcome of this study, did not significantly differ between the two groups (15.7% vs. 13.2%, aspirin vs. ticagrelor, p = .71). The incidence of vein grafts with any disease (stenosis or occlusion) did not significantly differ between the groups (19.4% vs. 19.8%, aspirin vs. ticagrelor, p = 1.00), and the number of patients with vein graft disease did not significantly differ between the groups (30.0% vs. 29.0%, aspirin vs. ticagrelor, p = 1.00). Vein grafts developing new disease did not significantly differ between the two groups (1.5% vs. 3.8%, aspirin vs. ticagrelor, p = .41). Freedom from major adverse cardiovascular events at 2 years was similar between the groups (p = .75). CONCLUSION: Compared to conventional aspirin therapy, ticagrelor did not significantly reduce vein graft disease 2 years after CABG.

Impact of lipid levels and high-intensity statins on vein graft patency after CABG: Midterm results of the ACTIVE trial.

BACKGROUND: High-dose atorvastatin did not improve 1-year vein graft patency in the recent Aggressive Cholesterol Therapy to Inhibit Vein Graft Events trial. However, it remains unknown whether high-intensity statins may impact graft disease in the years that follow. METHODS: In the trial, patients (N = 173) were randomized to receive atorvastatin 10 or 80 mg for 1 year after coronary bypass surgery (CABG). Beyond 1 year, the choice of statin was left to the patient's physician. In this study of participants who agreed to follow-up (N = 76), low-density lipoprotein (LDL) levels were measured and graft patency was assessed 3 years after surgery. RESULTS: The rate of vein graft disease 3 years after surgery was not significantly reduced with atorvastatin 80 mg during the first postoperative year or the use of open-label high-intensity statin thereafter (p = NS). However, a trend was observed between higher LDL levels during the first postoperative year and a greater incidence of vein graft disease at 3 years (p = .12). Among patients who had LDL levels more than 90 mg/dl in the first year after CABG, 38.5% had vein graft disease at 3 years, compared to 19.0% for those with LDL levels less than 90 mg/dl (p = .15). Higher mean LDL levels during the first postoperative year were associated with a higher rate of vein disease 3 years after surgery both at the graft level (p = .03) and at the patient level (p = .03) in multivariate analysis. CONCLUSIONS: Higher LDL levels during the first postoperative year were associated with significantly greater vein graft disease 3 years after CABG.

Intensive versus moderate statin therapy and early graft occlusion after coronary bypass surgery: The Aggressive Cholesterol Therapy to Inhibit Vein Graft Events randomized clinical trial.

OBJECTIVE: Statins prevent saphenous vein graft (SVG) disease and improve outcomes after coronary artery bypass graft surgery. However, the optimal postoperative statin dose remains unclear. The Aggressive Cholesterol Therapy to Inhibit Vein Graft Events trial was undertaken to evaluate whether early postoperative high-dose statin therapy reduces SVG occlusion compared with conventional moderate-dose therapy. METHODS: In this pilot, multicenter, double-blind randomized trial, 173 patients who had coronary artery bypass graft surgery with SVG were randomized to receive 10 mg or 80 mg atorvastatin daily for 1 year. The primary outcome was SVG occlusion at 1 year. Secondary outcomes were SVG stenosis and major adverse cardiovascular events. RESULTS: During trial enrollment, patients randomized to 80 mg atorvastatin achieved significantly lower low-density lipoprotein cholesterol levels (P < .00001). One-year graft assessment was performed in 145 patients (83.8%). The primary outcome, SVG occlusion at 1 year, did not significantly differ between the 2 groups (12.9% vs 11.4% for 10 mg atorvastatin vs 80 mg atorvastatin; P = .85). The incidence of vein graft stenosis also did not significantly differ between the groups (P = .54). However, there was a trend toward fewer patients developing vein graft disease (either occlusion or stenosis) in the 80 mg atorvastatin group (29.2% vs 19.2%, 10 mg atorvastatin vs 80 mg atorvastatin; P = .18). Freedom from major adverse cardiovascular events at 1 year was similar between the groups (P = .27). CONCLUSIONS: Compared with 10 mg atorvastatin, 80 mg atorvastatin did not significantly reduce vein graft occlusion 1 year after coronary artery bypass graft surgery in this pilot trial.

Impact of ticagrelor versus aspirin on graft patency after CABG: Rationale and design of the TARGET (ticagrelor antiplatelet therapy to reduce graft events and thrombosis) randomized controlled trial (NCT02053909).

RATIONALE: Saphenous vein graft disease remains a major limitation of coronary artery bypass graft surgery (CABG). Up to 20% of vein grafts will occlude within the first year after CABG despite standard aspirin antiplatelet therapy. However, more potent postoperative platelet inhibition with ticagrelor may improve graft patency. The goal of this study will be to evaluate the efficacy of ticagrelor, as compared to aspirin, for the prevention of saphenous vein graft occlusion following CABG. STUDY DESIGN: The Ticagrelor Antiplatelet Therapy to Reduce Graft Events and Thrombosis (TARGET) study is a multi-center double-blind randomized controlled trial enrolling patients who have undergone multi-vessel CABG with at least one saphenous vein graft. Patients are being randomized to receive either aspirin 81 mg twice per day or ticagrelor 90 mg twice per day for 2 years starting within 7 days after surgery. The projected enrollment is 150 patients in each arm (300 total patients). Patients will undergo computed tomography (CT) coronary angiography at 1 and 2 years after surgery to assess the incidence of vein graft occlusion and stenosis. CONCLUSION: To our knowledge, this trial is the first prospective study to evaluate the impact of early postoperative ticagrelor on 1- and 2-year graft patency after CABG. Furthermore, it is also the first trial to use a novel antiplatelet agent as a standalone, without aspirin, after CABG. Should ticagrelor reduce the incidence of postoperative graft occlusion, the results of this study will redefine modern antiplatelet management following coronary bypass surgery (ClinicalTrials.govNCT02053909).

Intensive versus moderate atorvastatin therapy and one-year graft patency after CABG: Rationale and design of the ACTIVE (Aggressive Cholesterol Therapy to Inhibit Vein Graft Events) randomized controlled trial (NCT01528709).

RATIONALE: Saphenous vein graft disease remains a major limitation of coronary artery bypass graft surgery (CABG). Statin therapy inhibits the development of vein graft disease and improves outcomes after CABG. However, it is unclear whether treatment with high-dose statins will further slow the process of vein graft disease and improve graft patency, as compared to conventional moderate doses. Therefore, the goal of this study will be to evaluate the efficacy of high-dose statin therapy versus moderate-dose statin therapy for the prevention of saphenous vein graft occlusion following CABG. STUDY DESIGN: The Aggressive Cholesterol Therapy to Inhibit Vein Graft Events (ACTIVE) trial is a multi-center double-blind randomized controlled trial enrolling patients who have undergone multi-vessel CABG with at least one saphenous vein graft. Patients will be randomized to receive either atorvastatin 80mg daily or atorvastatin 10mg daily for one year starting within 5days after surgery. The target enrollment is 100 patients in each arm (200 patients total). Lipid levels will be assessed every 3months. After one year, patients will undergo computed tomography (CT) coronary angiography to assess the incidence of vein graft occlusion and stenosis. CONCLUSION: This trial is the first prospective study to evaluate the impact of early postoperative high-dose statin therapy on graft patency after CABG. Should high-dose statin therapy reduce the incidence of postoperative graft occlusion, the results will add to the growing evidence supporting the role of high-intensity statins for modern lipid management after coronary surgical revascularization (ClinicalTrials.govNCT01528709).