Possibly greater reduction in MACE after patient selection for extended DAPT
New analyses from the PEGASUS-TIMI 54 trial suggest that a patient selection strategy excluding patients with predictors of bleeding and then stratifying based on number of ischemic risk factors may identify a large subgroup of patients (59%) with the potential to derive greater reductions in MACE from long-term treatment with ticagrelor 60 mg, with a lower risk of bleeding than the overall cohort in the trial PEGASUS-TIMI 54 (PrEvention with TicaGrelor of SecondAry Thrombotic Events in HighRiSk Patients with Prior AcUte Coronary Syndrome – Thrombolysis In Myocardial Infarction Study Group). These findings help advance the clinical understanding of the role of dual-antiplatelet therapy (DAPT) in the treatment of post-MI patients beyond the initial 12 months of treatment for acute coronary syndrome (ACS).
One new post-hoc sub-analysis of the PEGASUS-TIMI 54 study examined the efficacy and safety of long-term treatment with ticagrelor 60 mg and 90 mg or placebo twice daily, on a background of low-dose aspirin therapy (75-150 mg daily) in 21,162 post-MI patients with vs. without a history of coronary stenting. The relative risk reduction (RRR) in MACE with ticagrelor (pooled doses) was consistent in patients without (18% RRR) and with (15% RRR) prior coronary stenting (P-interaction=0.95). Given the higher baseline CV risk, patients without a history of coronary stenting demonstrated a higher absolute risk reduction in MACE (2.1% vs. 1.0%).
These data indicate that long-term treatment with ticagrelor plus acetylsalicylic acid (ASA or aspirin) may be equally beneficial in reducing relative risk of MACE in patients with or without prior coronary stenting and indicate that the potential benefit of extended DAPT may be driven through reduction of new coronary atherothrombotic events, rather than stent protection alone.
A second post-hoc analysis of the PEGASUS-TIMI 54 trial (n=13,938) explored whether clinical characteristics predicting bleeding and ischemic risk, identify subgroups of patients who may derive greater reductions in the rate of MACE from long-term treatment with ticagrelor 60 mg plus ASA or ASA alone, with a lower rate of major bleeding than the overall cohort in PEGASUS. Patients were grouped according to the presence or absence of predictors of bleeding events and ischemic risk factors. 59% of patients had no predictors of bleeding events and at least 2 ischemic risk factors.
In these patients, ticagrelor 60 mg significantly reduced the rate of MACE events by 1.9% (NNT=52) whilst increasing the rate of major bleeding by 1.0% (NNH= 102). In this subgroup ticagrelor also significantly reduced the risk of CV death (HR 0.66, P=0.0034, ARR 1.2%) and all-cause death (HR 0.75, P=0.018, ARR 1.1%). The risk reduction in CV and all-cause death did not reach statistical significance when looking at the overall PEGASUS patient population without grouping patients according to risk predictors. 19% of patients had a predictor of bleeding events. In these patients, treatment with ticagrelor 60 mg did not reduce the MACE event rate vs ASA alone but did increase the rate of major bleeding by 2.2%. 22% of patients had no predictors of bleeding events and 0 or 1 ischemic risk factors. In these patients, treatment with ticagrelor 60 mg reduced the MACE event rate by 0.5% vs ASA alone, but increased rate of major bleeding by 1%.