Abstract 16658: Patient Selection for Long-Term Secondary Prevention With Ticagrelor: Insights From PEGASUS-TIMI 54

Introduction: Long-term treatment with ticagrelor 60 mg added to ASA reduces ischemic risk but increases bleeding in patients with prior MI. Hypothesis: Clinical characteristics predicting bleeding and ischemic risk respectively applied in PEGASUS-TIMI 54 (NCT01225562) will identify subgroups who derive greater benefit with lower risk Methods: Predictors of bleeding (anemia at baseline, prior hospitalization for bleeding) and subgroups associated with greater ischemic risk reduction were merged into a selection algorithm. Efficacy (PEP - CV death, MI or stroke), safety (TIMI major bleeding) and net outcomes (CV death, MI, stroke, ICH or fatal bleeding) of ticagrelor 60 mg were evaluated by risk group. Results: Patients (N=13938) were divided into 4 groups first by the presence of a bleeding predictor (High Bleeding Risk - HBR, N=2703, 19%) and then the remainder (Low Bleeding Risk - LBR, N=11235, 81%) divided by the number of ischemic risk factors. In those with HBR, ticagrelor did not reduce the PEP (ARD 0.0%) but did increase bleeding by 2.2%. Of those with LBR, 22% had only 0 or 1 ischemic risk indicators, and in this subgroup ticagrelor reduced PEP by 0.5%, but increased bleeding by 1.0%. The remaining 59% of patients had no bleeding risk indicators and at least 2 ischemic risk indicators, and in this subgroup ticagrelor significantly reduced the risk of the PEP by 1.9% (P=0.0024, NNT 52) and only increased bleeding by 1.0% (P<0.0001, NNH 102). In this latter subgroup, ticagrelor significantly reduced CV death (HR 0.66, 95% CI 0.50 - 87, p=0.0034, ARR 1.2%) and all-cause mortality (HR 0.75, 95% CI 0.61 - 0.95, p=0.018, ARR 1.1%) and the net outcomes (HR 0.80, 95% CI 0.68 - 0.93, p=0.0031, ARR 1.9%). Conclusions: A patient selection strategy first identifying those at low bleeding risk and then stratifying according to number of ischemic high-risk features identifies a population that derives significant ischemic benefit with reductions in all-cause mortality and net outcomes.