Prognosis impact of ticagrelor vs clopidogrel based DAPT discontinuation after acute coronary syndrome. Insights from the multicenter CREA ARIAM Andalucia registry

Type of funding sources: Private company. Main funding source(s): The study project was financially supported by a non-conditional grant by Astrazeneca.

Premature cessation of dual antiplatelet therapy (DAPT) after acute coronary syndrome (ACS) has been associated with increased risk of major adverse cardiovascular events (MACE)

To assess the relationship between premature DAPT discontinuation versus therapy continuation and outcomes in ACS patients discharged on ticagrelor or clopidogrel.

Prospective, observational, multicentre all-comers registry of ACS patients who were intended to receive 12-month DAPT with ticagrelor or clopidogrel. Adherence was defined by the medication possession ratio metric (MPA, proportion of days of medication supply within a time interval). Categories for DAPT cessation included: physician-recommended discontinuation, brief interruption (invasive procedures), or disruption due to non-compliance or because of bleeding. Fully-adjusted Cox models with time-varying covariates to account for informative censoring, were used to examine the effect of DAPT cessation on MACE (a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, definite stent thrombosis, or target-lesion revascularization). Moderation analysis was also performed to assess for potential exposure-adherence interaction.

Among 2070 patients included (mean age 63 years, 73% men), 150 (7.3%) prematurely discontinued DAPT, median (IQR) 214 (101-236) days. Significantly more clopidogrel than ticagrelor users discontinued medication (9.5% vs 5%, respectively; P = .001), though timing of cessation was similar in both groups. At 1 year, MPR was slightly higher, but not significantly different, in the clopidogrel group than in the ticagrelor group (70±30 vs 64±29; P = .06). Overall, physician-guided discontinuation and bleeding were the main reasons for DAPT cessation. These were observed with a similar rate in both groups, while non-compliant disruption was more common among ticagrelor- than clopidogrel-treated patients (8% vs 2%, respectively; P for trend .04). After adjustments, DAPT cessation was associated with significantly increased risk of MACE (adjusted HR 2.94; 95% CI 1.82 – 4.74; P < .0001), regardless of the P2Y12 inhibitor (P interaction = 0.665). Non-compliance related cessation resulted in higher risk of MACE (HR 6.04, 95%CI 2.15 – 16.95; P = .001).

Overall, approximately 7% of patients discontinued DAPT. Early cessation of either ticagrelor- or clopidogrel-based DAPT portended to a near 3-fold increased risk of MACE. Disruption due to non-compliance resulted in higher risk for ischemic events. These data warrant efforts to focus on patient education in subgroups at high risk of non-compliance.