Evaluation of Systolic Blood Pressure, Use of Aspirin and Clopidogrel, and Stroke Recurrence in the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke Trial

Abstract

Importance: Elevated systolic blood pressure (SBP) after acute ischemic stroke and transient ischemic attack (TIA) is associated with future stroke risk.

Objective: To explore the association of dual antiplatelet therapy (DAPT) with stroke recurrence among patients with acute ischemic stroke and TIA with or without elevated baseline SBP.

Design, setting, and participants: This cohort study performed a post hoc subgroup analysis of the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, which was a multicenter trial conducted from 2010 to 2018 at 269 sites in 10 countries in North America, Europe, Australia, and New Zealand. Patients enrolled in POINT with available blood pressure and outcome data were included in this cohort. Statistical analysis was performed from November 2020 to January 2021.

Exposures: Baseline SBP less than 140 mm Hg vs greater than or equal to 140 mm Hg and the interaction term of SBP (<140 mm Hg vs ≥140 mm Hg) × treatment group (aspirin vs DAPT).

Main outcomes and measures: The primary outcome was ischemic stroke during 90 days of follow-up. The statistical analysis fit Cox proportional hazards models adjusted for patient age, race, premorbid hypertension, diabetes, and final diagnosis of the qualifying event (stroke vs TIA).

Results: Among 4781 patients in the cohort, the mean (SD) age was 64.6 (13.1) years; 2142 (44.8%) were male individuals, 3487 (72.9%) were White individuals, and 266 (5.6%) had a primary outcome of ischemic stroke during follow-up. There were 946 patients (19.8%) with baseline SBP less than 140 mm Hg and 3835 (80.2%) with SBP greater than or equal to 140 mm Hg. The interaction term (SBP × treatment) was significant (P for interaction = .03). In the subgroup of patients with SBP less than 140 mm Hg, the hazard ratio (HR) of DAPT vs aspirin alone for ischemic stroke was 0.36 (95% CI, 0.18-0.72; P = .004), whereas the HR in the subgroup with SBP greater than or equal to 140 mm Hg was 0.79 (95% CI, 0.60-1.02; P = .08). When evaluating the outcome of ischemic stroke within 7 days of randomization, the interaction term was significant (P for interaction = .02), and the HR for patients with DAPT with SBP less than 140 mm Hg was 0.19 (95% CI, 0.07-0.55; P = .002).

Conclusions and relevance: In the POINT trial, patients with SBP less than 140 mm Hg at presentation received a greater benefit from 90 days of DAPT than those with higher baseline SBP, particularly for reduction of early ischemic stroke recurrence. Additional research is needed to replicate these findings and potentially test whether mild SBP reduction and DAPT within 12 hours of stroke onset lowers early risk of stroke recurrence.

Figure 1.. Kaplan-Meier Curves for Ischemic Stroke Events Within 90 Days, Stratified by First Measured Systolic Blood Pressure (SBP) Level With Failure Rates for Aspirin and Dual Antiplatelet Therapy

Figure 2.. Kaplan-Meier Curves for Ischemic Stroke Events Within 90 Days, Stratified by Final Diagnosis of the Baseline Qualifying Event and First Measured Systolic Blood Pressure (SBP) With Failure Rates for Aspirin and Dual Antiplatelet Therapy

TIA denotes transient ischemic attack.