Time Course for Benefit and Risk of Ticagrelor and Aspirin in Acute Ischemic Stroke or Transient Ischemic Attack.

Abstract

BACKGROUND AND OBJECTIVES:

The goal of this work was to investigate the short-term time-course benefit and risk of ticagrelor with aspirin in acute mild-moderate ischemic stroke or high-risk TIA in The Acute Stroke or Transient Ischemic Attack Treated with Ticagrelor and ASA for Prevention of Stroke and Death (THALES) trial.

METHODS:

In an exploratory analysis of the THALES trial, we evaluated the cumulative incidence of irreversible efficacy and safety outcomes at different time points during the 30-day treatment period. The efficacy outcome was major ischemic events defined as a composite of ischemic stroke or nonhemorrhagic death. The safety outcome was major hemorrhage defined as a composite of intracranial hemorrhage and fatal bleedings. Net clinical impact was defined as the combination of these 2 endpoints.

RESULTS:

This analysis included a total of 11,016 patients (5,523 in the ticagrelor-aspirin group, 5,493 in the aspirin group) with a mean age of 65 years, and 39% were women. The reduction of major ischemic events by ticagrelor occurred in the first week (4.1% vs 5.3%; absolute risk reduction 1.15%, 95% CI 0.36%-1.94%) and remained throughout the 30-day treatment period. An increase in major hemorrhage was seen during the first week and remained relatively constant in the following weeks (absolute risk increase ≈0.3%). Cumulative analysis showed that the net clinical impact favored ticagrelor-aspirin in the first week (absolute risk reduction 0.97%, 95% CI, 0.17%-1.77%) and remained constant throughout the 30 days.

DISCUSSION:

In patients with mild-moderate ischemic stroke or high-risk TIA, the treatment effect of ticagrelor-aspirin was present from the first week. The ischemic benefit of ticagrelor-aspirin outweighs the risk of major hemorrhage throughout the treatment period, which may support the use of 30-day treatment with ticagrelor and aspirin in these patients.

CLASSIFICATION OF EVIDENCE:

This study provides Class II evidence that, for patients with mild-moderate ischemic stroke or high-risk TIA, the ischemic benefit of ticagrelor-aspirin outweighs the risk of major hemorrhage throughout the 30-day treatment period.

• Authors: Yongjun Wang, Yuesong Pan, Hao Li, Pierre Amarenco, Hans Denison, Scott R Evans, Anders Himmelmann, Stefan James, Mikael Knutsson, Per Ladenvall, Carlos A Molina, S Claiborne Johnston
• Journal: Neurology (Neurology) Vol. 99 Issue 1 Pg. e46-e54 (07 05 2022) ISSN: 1526-632X [Electronic] United States
• PMID: 35437261 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Chemical References

• Platelet Aggregation Inhibitors
• Ticagrelor
• Aspirin

Topics

• Aged
• Aspirin (therapeutic use)
• Drug Therapy, Combination
• Female
• Hemorrhage (chemically induced, epidemiology)
• Humans
• Ischemia
• Ischemic Attack, Transient (chemically induced, drug therapy, epidemiology)
• Ischemic Stroke (drug therapy, epidemiology)
• Male
• Platelet Aggregation Inhibitors (adverse effects)
• Stroke (drug therapy, epidemiology, prevention & control)
• Ticagrelor (therapeutic use)