A high-risk SPI-II score identified a patient subgroup that derived a greater absolute risk reduction of 2.80% for ischemic stroke when treated with dual-antiplatelet therapy compared to aspirin.
RCT (n=4,841)
Double-blind
Randomized
Yes
Does short-term clopidogrel-aspirin (DAPT) reduce incident ischemic stroke compared to aspirin alone in patients with transient ischemic attack and minor ischemic stroke?
Stratification by baseline stroke risk using the SPI-II score identifies a subgroup of patients with TIA or minor stroke who derive greater absolute benefit from DAPT, despite a higher absolute risk of major hemorrhage.
Effect estimate: HR 0.64 (95% CI 0.46-0.88)
p-value: p=0.007
BACKGROUND: High-risk transient ischemic attacks and minor ischemic strokes are followed by a variable risk of ischemic stroke. We aimed to determine how baseline stroke risk modified the efficacy of clopidogrel-aspirin (referred to here as dual-antiplatelet therapy DAPT) for transient ischemic attack and minor ischemic stroke. METHODS: We performed an unplanned secondary analysis of the POINT trial (Platelet-Oriented Inhibition in New Transient Ischemic Attack and Minor Ischemic Stroke). We first evaluated the associations of the CHA 2 DS 2 -VASc and stroke prognosis instrument II (SPI-II) scores with the risk of incident ischemic stroke and major hemorrhage (intracranial hemorrhage or major systemic hemorrhage). We then tested for heterogeneity of the relative and absolute treatment effect of DAPT relative to aspirin across low- and high-risk patient subgroups. RESULTS: A total of 4841 trial participants were included in this analysis, with 2400 participants assigned to treatment with short-term DAPT and 2430 participants to treatment with aspirin and placebo. The dichotomized SPI-II score, but not the CHA 2 DS 2 -VASc score ( P =0.18), was associated with the risk of incident ischemic stroke. A high-risk SPI-II score (>3) was associated with greater risk of incident ischemic stroke (hazard ratio of incident ischemic stroke relative to low-risk SPI-II score of 1.84 95% CI, 1.44–2.35; P <0.001) and numerically greater risk of major hemorrhage though not meeting statistical significance (hazard ratio, 1.80 95% CI, 0.90–3.57; P =0.10). The relative risk reduction with DAPT was similar across SPI-II strata ( P interaction =0.31). The absolute risk reduction for ischemic stroke with DAPT compared with aspirin was nearly 4-fold higher (2.80% versus 0.76%; number needed to treat, 31 versus 131) in the high-risk SPI-II stratum relative to the low-risk stratum. The absolute risk increase for major hemorrhage with DAPT compared with aspirin was 3-fold higher (0.84% versus 0.30%; number needed to harm, 119 versus 331) in the high-risk SPI-II stratum relative to the low-risk stratum. CONCLUSIONS: Stratification by baseline stroke risk identifies a patient subgroup that derives greater absolute benefit from treatment with DAPT. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00991029.
Daghlas et al. (2024) conducted an RCT in High-risk transient ischemic attacks (TIA) and minor ischemic strokes (n=4,841). Dual-antiplatelet therapy (clopidogrel and aspirin) vs. Aspirin 50mg-325mg and placebo was evaluated on Incident ischemic stroke within 90 days (High-risk SPI-II stratum) (HR 0.64, 95% CI 0.46-0.88, p=0.007). A high-risk SPI-II score identified a patient subgroup that derived a greater absolute risk reduction of 2.80% for ischemic stroke when treated with dual-antiplatelet therapy compared to aspirin.