Time to treatment and disability attributed to index stroke in the POINT trial

J Stroke Cerebrovasc Dis. 2024 Nov;33(11):107988. doi: 10.1016/j.jstrokecerebrovasdis.2024.107988. Epub 2024 Sep 1.

Abstract

Background: In the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, dual antiplatelet therapy (DAPT) was associated with reduced disability attributable to the index stroke compared to antiplatelet monotherapy. However, it is unknown whether earlier treatment with DAPT versus aspirin is associated with greater benefit.

Methods: We analyzed patients enrolled in POINT with minor ischemic stroke who had available data recording the treatment initiation time and modified Rankin Scale (mRS) at 90 days. Patients were randomized to DAPT (aspirin plus clopidogrel) vs. aspirin alone within 12 h of symptom onset. We estimated the effect of DAPT on disability (defined as mRS>1) ascribed to the index event and major hemorrhage at 90 days, stratified by tertiles of time from symptom onset-to-treatment-initiation.

Results: A total of 2559 patients were included; median onset-to-treatment-initiation time was 8.3 h (IQR:5.8-11.0). Comparing DAPT to aspirin, the rate of disability attributed to the index event at 90-day follow-up was 5.1 % vs. 8.6 % (OR 0.57; 95 % CI:0.33-0.99) in patients treated <6.7 h, 7.5 % vs. 9.9 % (OR 0.74; 95 % CI:0.45-1.19) in those treated 6.7-10.0 h, and 8.6 % vs. 10.6 % (OR 0.80; 95 % CI:0.50-1.26) in those treated >10.0 h after symptom onset (p for interaction=0.65). There was no difference in major hemorrhage across time strata.

Conclusions: While not statistically significant, these results suggest the possibility of greater efficacy at reducing disability ascribed to minor stroke with earlier treatment with DAPT compared to aspirin.

Registration: URL: https://www.

Clinicaltrials: gov; Identifier: NCT00991029.

Keywords: Aspirin; Clopidogrel; Dual anti-platelet therapy; Ischemic stroke; Stroke.

Publication types

  • Randomized Controlled Trial
  • Comparative Study
  • Multicenter Study

MeSH terms

  • Aged
  • Aspirin* / administration & dosage
  • Aspirin* / adverse effects
  • Aspirin* / therapeutic use
  • Clopidogrel* / adverse effects
  • Clopidogrel* / therapeutic use
  • Disability Evaluation*
  • Dual Anti-Platelet Therapy* / adverse effects
  • Female
  • Functional Status*
  • Humans
  • Ischemic Attack, Transient / diagnosis
  • Ischemic Attack, Transient / drug therapy
  • Ischemic Attack, Transient / physiopathology
  • Ischemic Stroke* / diagnosis
  • Ischemic Stroke* / drug therapy
  • Ischemic Stroke* / physiopathology
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors* / adverse effects
  • Platelet Aggregation Inhibitors* / therapeutic use
  • Recovery of Function
  • Risk Factors
  • Time Factors
  • Time-to-Treatment*
  • Treatment Outcome

Substances

  • Aspirin
  • Platelet Aggregation Inhibitors
  • Clopidogrel

Associated data

  • ClinicalTrials.gov/NCT00991029