Ticagrelor and Outcomes for Patients With Prior CABG
Background Patients with prior coronary artery bypass graft surgery (CABG) who present with an acute coronary syndrome have a high risk for recurrent events. Whether intensive antiplatelet therapy with ticagrelor might be beneficial compared with clopidogrel is unknown. In this substudy of the PLATO trial, we studied the effects of randomized treatment dependent on history of CABG.
Methods Patients participating in PLATO were classified according to whether they had undergone prior CABG. The trial's primary and secondary end points were compared using Cox proportional hazards regression.
Results Of the 18,613 study patients, 1,133 (6.1%) had prior CABG. Prior-CABG patients had more high-risk characteristics at study entry and a 2-fold increase in clinical events during follow-up, but less major bleeding. The primary end point (composite of cardiovascular death, myocardial infarction, and stroke) was reduced to a similar extent by ticagrelor among patients with (19.6% vs 21.4%; adjusted hazard ratio [HR], 0.91 [0.67, 1.24]) and without (9.2% vs 11.0%; adjusted HR, 0.86 [0.77, 0.96]; Pinteraction = .73) prior CABG. Major bleeding was similar with ticagrelor versus clopidogrel among patients with (8.1% vs 8.7%; adjusted HR, 0.89 [0.55, 1.47]) and without (11.8% vs 11.4%; HR, 1.08 [0.98, 1.20]; Pinteraction = .46) prior CABG.
Conclusions Prior-CABG patients presenting with acute coronary syndrome are a high-risk cohort for death and recurrent cardiovascular events but have a lower risk for major bleeding. Similar to the results in no-prior-CABG patients, ticagrelor was associated with a reduction in ischemic events without an increase in major bleeding.
Patients with prior coronary artery bypass graft surgery (CABG) who present with an acute coronary syndrome (ACS) have a high risk for immediate and recurrent cardiovascular events and death. Although guideline-based treatment, especially intensive lipid-lowering therapy, may be beneficial, additional therapies are needed to reduce the high residual risk.
Prior-CABG patients may benefit from intensive antithrombotic and antiplatelet therapies. After the initial 5 years after CABG, recurrent cardiovascular events are mostly due to saphenous vein graft (SVG) failure and often result in SVG occlusion. Saphenous vein graft disease is difficult to treat because of high rates of restenosis and progression of disease in nonstented SVG segments and has been associated with poor prognosis.
Ticagrelor is a reversible and direct-acting oral antagonist of the adenosine diphosphate receptor P2Y12 that provides faster, greater, and more consistent P2Y12 inhibition than clopidogrel. The PLATelet inhibition and patient Outcomes (PLATO) trial demonstrated significant reduction with ticagrelor in the incidence of cardiovascular death, myocardial infarction (MI), and nonfatal stroke as well as all-cause mortality among ACS patients. The goal of the present analysis was to examine the outcomes and the effect of ticagrelor compared with clopidogrel among prior-CABG ACS patients enrolled in PLATO.
Abstract and Introduction
Abstract
Background Patients with prior coronary artery bypass graft surgery (CABG) who present with an acute coronary syndrome have a high risk for recurrent events. Whether intensive antiplatelet therapy with ticagrelor might be beneficial compared with clopidogrel is unknown. In this substudy of the PLATO trial, we studied the effects of randomized treatment dependent on history of CABG.
Methods Patients participating in PLATO were classified according to whether they had undergone prior CABG. The trial's primary and secondary end points were compared using Cox proportional hazards regression.
Results Of the 18,613 study patients, 1,133 (6.1%) had prior CABG. Prior-CABG patients had more high-risk characteristics at study entry and a 2-fold increase in clinical events during follow-up, but less major bleeding. The primary end point (composite of cardiovascular death, myocardial infarction, and stroke) was reduced to a similar extent by ticagrelor among patients with (19.6% vs 21.4%; adjusted hazard ratio [HR], 0.91 [0.67, 1.24]) and without (9.2% vs 11.0%; adjusted HR, 0.86 [0.77, 0.96]; Pinteraction = .73) prior CABG. Major bleeding was similar with ticagrelor versus clopidogrel among patients with (8.1% vs 8.7%; adjusted HR, 0.89 [0.55, 1.47]) and without (11.8% vs 11.4%; HR, 1.08 [0.98, 1.20]; Pinteraction = .46) prior CABG.
Conclusions Prior-CABG patients presenting with acute coronary syndrome are a high-risk cohort for death and recurrent cardiovascular events but have a lower risk for major bleeding. Similar to the results in no-prior-CABG patients, ticagrelor was associated with a reduction in ischemic events without an increase in major bleeding.
Introduction
Patients with prior coronary artery bypass graft surgery (CABG) who present with an acute coronary syndrome (ACS) have a high risk for immediate and recurrent cardiovascular events and death. Although guideline-based treatment, especially intensive lipid-lowering therapy, may be beneficial, additional therapies are needed to reduce the high residual risk.
Prior-CABG patients may benefit from intensive antithrombotic and antiplatelet therapies. After the initial 5 years after CABG, recurrent cardiovascular events are mostly due to saphenous vein graft (SVG) failure and often result in SVG occlusion. Saphenous vein graft disease is difficult to treat because of high rates of restenosis and progression of disease in nonstented SVG segments and has been associated with poor prognosis.
Ticagrelor is a reversible and direct-acting oral antagonist of the adenosine diphosphate receptor P2Y12 that provides faster, greater, and more consistent P2Y12 inhibition than clopidogrel. The PLATelet inhibition and patient Outcomes (PLATO) trial demonstrated significant reduction with ticagrelor in the incidence of cardiovascular death, myocardial infarction (MI), and nonfatal stroke as well as all-cause mortality among ACS patients. The goal of the present analysis was to examine the outcomes and the effect of ticagrelor compared with clopidogrel among prior-CABG ACS patients enrolled in PLATO.
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