PCISOS Risk Profiles Stratify Heterogeneous Outcomes in Minor Posterior Circulation Ischemic Stroke: A Post Hoc Analysis of the CHANCE-2 Trial

BACKGROUND: Risk stratification in posterior circulation ischemic stroke (PCIS) is challenging. Although the Posterior Circulation Ischemic Stroke Outcome Score (PCISOS) was developed to address this, its utility in minor PCIS and in identifying homogeneous populations for clinical trials or treatment-responsive subgroups remains uncertain. METHODS: CHANCE-2 (Ticagrelor or Clopidogrel With Aspirin in High-Risk Patients With Acute Nondisabling Cerebrovascular Events II) was a multicenter, randomized trial that enrolled patients with minor stroke or high-risk transient ischemic attack who carried CYP2C19 loss-of-function alleles. Patients received ticagrelor-aspirin or clopidogrel-aspirin. This secondary analysis included patients with PCIS, stratified into low- (≤15), intermediate- (16–20), and high-risk (≥21) groups based on PCISOS. The primary outcome was 90-day stroke recurrence. Outcomes were analyzed using Cox and logistic regression models, adjusting for significantly imbalanced baseline covariates relevant to each comparison. RESULTS: Among 1379 patients with PCIS (median age, 64.0 [56.6–70.7] years; 67.4% male), 90-day stroke recurrence occurred in 6.0%, 8.2%, and 18.5% of the low-, intermediate-, and high-risk PCISOS groups, respectively ( P <0.001). Risk increased progressively (adjusted hazard ratio for intermediate-risk, 1.32 [95% CI, 0.87–2.02]; high-risk, 3.02 [95% CI, 1.52–6.02]; P trend =0.008). Similar associations were observed for modified Rankin Scale score of 2 to 6 outcomes (adjusted odds ratio for intermediate-risk, 2.21 [95% CI, 1.28–3.84]; high-risk, 3.53 [95% CI, 1.42–8.74]; P trend <0.001). A treatment-by-risk interaction was observed: ticagrelor-aspirin reduced the modified Rankin Scale score of 1 to 6 rates in low- and intermediate-risk patients, but not in high-risk patients ( P interaction =0.03). Favorable outcome (modified Rankin Scale score of 0–1) was more common in patients with PCISOS ≤15 than in those with National Institutes of Health Stroke Scale score ≤3 ( P =0.02). CONCLUSIONS: PCISOS provides effective risk stratification in minor PCIS, identifying subgroups with heterogeneous outcome risks and differential response to ticagrelor-aspirin. Patients with PCISOS ≥21, a high-risk subgroup within National Institutes of Health Stroke Scale–defined minor strokes, remain underexplored and may benefit from tailored strategies in future trials. A threshold of PCISOS ≤15 may more accurately define truly low-risk patients than National Institutes of Health Stroke Scale score ≤3, thereby improving trial efficiency and advancing precision in PCIS research. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04078737.