POINT Trial: DAPT in International Population
In patients with high-risk TIA or minor ischemic stroke presenting within 12 hours, does dual antiplatelet therapy with clopidogrel plus aspirin reduce major ischemic events at 90 days compared with aspirin monotherapy?
Johnston et al. (NEJM 2018) · doi:10.1056/NEJMoa1800410 · 4,881 patients
Population
Included
- Age 18 years or older
- Minor ischemic stroke (NIHSS 0 to 3) or high-risk TIA (ABCD2 score 4 or higher)
- Randomization within 12 hours of symptom onset
- No clear indication for anticoagulation
- Independent at baseline (mRS 0 to 2)
Eligible patients
- At least 18 years of age
- Randomization within 12 hours after an acute ischemic stroke with an NIHSS score of 3 or less (range 0 to 42)
- Or a high-risk TIA with an ABCD2 score of 4 or more (range 0 to 7)
- Required CT or MRI to rule out intracranial bleeding or other explanatory conditions and detect contraindications
Excluded
- Hemorrhagic stroke on baseline imaging
- Severe stroke (NIHSS 4 or higher)
- Low-risk TIA (ABCD2 below 4)
- Indication for anticoagulation (atrial fibrillation)
- Recent major surgery or GI bleeding
- Contraindication to clopidogrel or aspirin
TIA mimics / prior thrombolysis
- Symptoms limited to isolated numbness, isolated visual changes, or isolated dizziness or vertigo
- Received any thrombolytic therapy within 1 week before the event
Reperfusion candidacy
- Candidates for thrombolysis, endovascular therapy, or endarterectomy
Antithrombotic / anticoagulation
- Planned antiplatelet or anticoagulation therapy (including presumed atrial fibrillation or cardiovascular disease where anticoagulation is indicated)
- A contraindication to aspirin or clopidogrel
- Anticipated NSAID use for more than 7 days during the trial
Source: Johnston SC et al., N Engl J Med 2018· Retrieved 2026-06-09
Primary Outcome
Negligible absolute difference
Major-event-free at 90 Days
Study Arms
- Agent
- Clopidogrel plus aspirin
- Dose
- Clopidogrel 600 mg loading on day 1, then 75 mg daily on days 2 to 90; plus open-label aspirin 50 to 325 mg daily (162 mg daily for 5 days then 81 mg daily recommended)
- Route
- Oral
- Frequency
- Once daily
- Duration
- Clopidogrel plus aspirin through day 90
- Co-interventions
- Open-label aspirin 50 to 325 mg daily in both groups, dose at physician discretion (162 mg x5 days then 81 mg recommended)
First dose as soon as possible after randomization; followed 90 days
- Agent
- Aspirin plus placebo clopidogrel
- Dose
- Placebo clopidogrel; plus open-label aspirin 50 to 325 mg daily (162 mg daily for 5 days then 81 mg daily recommended)
- Route
- Oral
- Frequency
- Once daily
- Duration
- Through day 90
- Co-interventions
- Open-label aspirin 50 to 325 mg daily in both groups, dose at physician discretion
Placebo matched clopidogrel appearance and taste
Safety
Major hemorrhage at 90 days
0.9%
0.4%
Major hemorrhage: 0.9% DAPT vs 0.4% aspirin (HR 2.32, 95% CI 1.10-4.87, P=0.02). Unlike CHANCE, POINT showed a statistically significant increase in major hemorrhage with 90-day dual therapy. This excess risk, concentrated after day 21, drove the guideline recommendation to limit DAPT to 21 days. Source: Johnston SC et al., NEJM 2018, Table 2.
Trial Design
Type
- Randomized double-blind international trial
- 1:1 allocation (DAPT vs. Aspirin)
Timeline
Enrolled 2010-2017
N
4,881
Enrollment
4,881 patients at 269 sites in 10 countries. Enrolled 2010 to 2017. Stopped early for efficacy at the prespecified 90-day interim analysis.
ClinicalTrials.gov
NCT00991029Bedside Pearl
POINT confirmed CHANCE in Western patients but showed major hemorrhage was significantly higher at 90 days (0.9% vs 0.4%, P=0.02). The hemorrhage excess emerged after day 21. Use the 21-day CHANCE protocol, not the 90-day POINT duration.