Background and Aims

In patients with acute mild-moderate ischemic stroke or high-risk transient ischemic attack (TIA) in the THALES trial, combination of ticagrelor and aspirin for 30 days reduced stroke or death but increased risk of severe bleeding in comparison to aspirin alone. We investigated the short-term time course for benefit and risk of ticagrelor-aspirin in these patients.

Methods

We evaluated the cumulative incidence of efficacy and safety of treatment for varying timepoints during 30-day follow-up. The efficacy outcome was major ischemic events defined as a composite of ischemic stroke or non-hemorrhagic death. The safety outcome was major hemorrhage defined as a composite of intracranial hemorrhage or fatal bleedings. Net clinical impact was defined as the combination of these two endpoints.

Results

The reduction of major ischemic events by ticagrelor occurred in the first week (4.1% vs 5.3%; absolute risk reduction [ARR] 1.15%, 95% CI 0.36% to 1.94%), and remained throughout the 30-day treatment period. An increase of major hemorrhage was seen during the first week which remained relatively constant in the following weeks (absolute risk increase, approximately 0.3%). Cumulative analysis showed that the net clinical impact favored ticagrelor-aspirin in the first week (ARR 0.97%, 95% CI, 0.17% to 1.77%) and remained constant throughout the 30 days.

Conclusions

In patients with mild-moderate ischemic stroke or high-risk TIA, net clinical benefit was seen in the first week and remained during the entire 30-day study period. This analysis supports 30 days of dual antiplatelet therapy with ticagrelor and aspirin in these patients.

TRIAL REGISTRATION

clinicaltrials.gov Identifiers: NCT03354429

Background and Aims

This study aimed to disentangle temporal course benefit and risk of ticagrelor-aspirin treatment in patients with a minor ischemic stroke or transient ischemic attack (TIA) who carried CYP2C19 loss-of-function (LOF) alleles in the CHANCE-2 (ticagrelor or Clopidogrel with aspirin in High- risk patients with Acute Non- disabling Cerebrovascular Events II) trial.

Methods

The efficacy outcome was major ischemic event defined as the composite of ischemic stroke or non-hemorrhagic death. The safety outcome included moderate-to-severe bleeding and any bleeding. Time course analyses of ischemic benefit and hemorrhagic risk were performed at different timepoints by week and time periods before and after 21 days.

Results

A total of 43, 3, 4 and 1 of 54 fewer major ischemic events and a total of 28, 38, 10 and 7 of 90 excess bleedings occurred in the ticagrelor-aspirin group at the first, second, third and fourth week, respectively. Whereas, the risk of moderate-to-severe bleeding was consistent low in the ticagrelor-aspirin group. The reduction of major ischemic events by ticagrelor-aspirin predominately occurred in the first week (absolute risk reduction 1.34%, 95% CI 0.29% to 2.39%) and attenuated but remained in the next three weeks. The absolute increase in bleeding seen in the first week (0.87%) remained in the next three weeks.

Conclusions

Among patients with minor ischemic stroke or TIA who were carriers of CYP2C19 LOF alleles, the benefit of ticagrelor-aspirin was present from the first week and persisted throughout 21-day period of dual antiplatelet therapy, supporting 21 days treatment with ticagrelor and aspirin in these patients.