Efficacy and Safety of Ticagrelor and Aspirin in Patients With Moderate Ischemic Stroke An Exploratory Analysis of the THALES Randomized Clinical Trial
Por:
Wang, YJ, Pan, YS, Li, H, Amarenco, P, Denison, H, Evans, SR, Himmelmann, A, James, S, Birve, F, Ladenvall, P, Molina, CA, Johnston, SC, Martí-Fàbregas J., Pham, Dinh Dai
Publicada:
1 sep 2021
Ahead of Print:
1 jul 2021
Resumen:
IMPORTANCE Prior trials of dual antiplatelet therapy excluded patients with moderate ischemic stroke. These patients were included in the Acute Stroke or Transient Ischaemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death (THALES) trial, but results have not been reported separately, raising concerns about safety and efficacy in this subgroup.
OBJECTIVE To evaluate the efficacy and safety of ticagrelor plus aspirin in patients with moderate ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score of 4 to 5).
DESIGN, SETTING, AND PARTICIPANTS The THALES trial was a randomized trial conducted at 414 hospitals in 28 countries in January 2018 and December 2019. This exploratory analysis compared patients with moderate stroke (baseline NIHSS score of 4 to 5) with patients with less severe stroke (NIHSS score of 0 to 3). A total of 9983 patients with stroke were included in the present analysis, after excluding 2 patients with NIHSS scores greater than 5 and 1031 patients with transient ischemic attack. Data were analyzed from March to April 2021.
INTERVENTIONS Ticagrelor (180-mg loading dose on day 1 followed by 90 mg twice daily on days 2 to 30) or placebo within 24 hours after symptom onset. All patients received aspirin, 300 to 325 mg, on day 1 followed by aspirin, 75 to 100 mg, daily on days 2 to 30. Patients were observed for 30 additional days.
MAIN OUTCOMES AND MEASURES The primary outcome was time to stroke or death within 30 days. The primary safety outcome was time to severe bleeding.
RESULTS In total, 3312 patients presented with moderate stroke and 6671 presented with less severe stroke. Of those in the moderate stroke group, 1293 (39.0%) were female, and the mean (SD) age was 64.5 (10.8) years; of those in the less severe stroke group, 2518 (37.7%) were female, and the mean (SD) age was 64.8 (11.2) years. The observed primary outcome event rate in patients with moderate stroke was 7.6%(129 of 1671) for those in the ticagrelor group and 9.1% (150 of 1641) for those in the placebo group (hazard ratio, 0.84; 95% CI, 0.66-1.06); the primary outcome event rate in patients with less severe stroke was 4.7%(158 of 3359) for those in the ticagrelor group and 5.7%(190 of 3312) for those in the placebo group (hazard ratio, 0.82; 95% CI, 0.66-1.01) (P for interaction = .88). Severe bleeding occurred in 8 patients (0.5%) in the ticagrelor group and in 4 patients (0.2%) in the placebo group in those with moderate stroke compared with 16 patients (0.5%) and 3 patients (0.1%), respectively, with less severe stroke (P for interaction = .26).
CONCLUSIONS AND RELEVANCE In this study, patients with a moderate ischemic stroke had consistent benefit from ticagrelor plus aspirin vs aspirin alone compared with patients with less severe ischemic stroke, with no further increase in the risk of intracranial bleeding or other severe bleeding events.
Filiaciones:
Wang, YJ:
Capital Med Univ, Beijing Tiantan Hosp, Dept Neurol, 119,South 4th Ring West Rd, Beijing 100070, Peoples R China
China Natl Clin Res Ctr Neurol Dis, Beijing, Peoples R China
Pan, YS:
Capital Med Univ, Beijing Tiantan Hosp, Dept Neurol, 119,South 4th Ring West Rd, Beijing 100070, Peoples R China
China Natl Clin Res Ctr Neurol Dis, Beijing, Peoples R China
Li, H:
Capital Med Univ, Beijing Tiantan Hosp, Dept Neurol, 119,South 4th Ring West Rd, Beijing 100070, Peoples R China
China Natl Clin Res Ctr Neurol Dis, Beijing, Peoples R China
Amarenco, P:
Univ Paris, BichatClaude Bernard Hosp, Dept Neurol, Paris, France
Univ Paris, BichatClaude Bernard Hosp, Stroke Ctr, Paris, France
Denison, H:
AstraZeneca, Biopharmaceut Res & Dev, Gothenburg, Sweden
Evans, SR:
George Washington Univ, Biostat Ctr, Washington, DC USA
Himmelmann, A:
AstraZeneca, Biopharmaceut Res & Dev, Gothenburg, Sweden
James, S:
Uppsala Univ, Dept Med Sci, Uppsala, Sweden
Birve, F:
AstraZeneca, Biopharmaceut Res & Dev, Gothenburg, Sweden
Ladenvall, P:
AstraZeneca, Biopharmaceut Res & Dev, Gothenburg, Sweden
Molina, CA:
Vall dHebron Hosp, Stroke Unit, Barcelona, Spain
Johnston, SC:
Univ Texas Austin, Dell Med Sch, 1912 Speedway,Ste 564, Austin, TX 78712 USA
Martí-Fàbregas J.:
Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
Pham, Dinh Dai:
Military Hospital 103, Hanoi, Vietnam
hybrid, Green Published
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