Admission systolic blood pressure and short-term outcomes after dual antiplatelet therapy in patients with minor ischemic stroke or transient ischemic attack

Abstract

Background: Elevated baseline systolic blood pressure (SBP) was associated with poor outcomes following dual antiplatelet therapy (DAPT) in patients with non-cardioembolic minor ischemic stroke (MIS) or high-risk transient ischemic attack (TIA) in clinical trials.

Objectives: We aimed to assess the impact of admission SBP on the short-term outcomes after DAPT in patients with non-cardioembolic MIS or high-risk TIA.

Methods: We performed an inverse probability weighted (IPW) analysis from a prospective multicentric real-world study (READAPT) including patients with non-cardioembolic MIS (National Institute of Health Stroke Scale of 0-5) or high-risk TIA (ABCD2 ⩾4) who initiated DAPT within 48 h of symptom onset. The primary effectiveness outcome was the 90-day risk of new ischemic stroke or other vascular events. The secondary effectiveness outcomes were the 90-day modified Rankin Scale score ordinal shift, vascular and all-cause mortality, 24-h early neurological improvement or deterioration. The safety outcomes included the 90-day risk of moderate-to-severe and any bleedings, symptomatic intracranial hemorrhage, and 24-h hemorrhagic transformation. We used Cox proportional hazards regression with restricted cubic splines to model the continuous relationship between SBP and the hazard ratio (HR) of new vascular events. We selected SBP = 124 mm Hg as cut-off point for the IPW weighting. Outcomes were compared using Cox and generalized logistic regression analyses, adjusted for residual confounders.

Results: From 2278 patients in the READAPT cohort, we included 1291 MIS or high-risk TIAs (mean age 70.6 ± 11.4 years; 65.8% males). After IPW, patients with admission SBP ⩾124 mm Hg versus <124 mm Hg had a significantly higher risk of 90-day ischemic stroke or other vascular events (adjusted HR: 2.14 (95% CI 1.07%-4.98%); p = 0.033) and of 24-h early neurological deterioration (adjusted risk difference: 1.91% (95% CI 0.60%-3.41%); p = 0.006). The overall risk of safety outcomes was low, although patients with SBP ⩾124 mm Hg on admission showed higher rates of 90-day moderate-to-severe and any bleeding events (adjusted risk difference: 1.24% (95% CI 0.38%-2.14%); p = 0.004 and 6.18% (95% CI 4.19%-8.16%); p < 0.001; respectively), as well as of 24-h hemorrhagic transformation (adjusted risk difference: 1.57% (95% CI 0.60%-2.55%); p = 0.001). Subgroup analysis showed a significant interaction between admission SBP, sex, and time to DAPT start in predicting 90-day new vascular events (p for interaction <0.001 and 0.007, respectively).

Conclusion: In patients with non-cardioembolic MIS or high-risk TIA, higher levels of admission SBP may be associated with an increased risk of new vascular events, early neurological deterioration, and bleeding after DAPT use. Future studies should further investigate if optimizing blood pressure management may further improve prognosis.

Keywords: blood pressure; dual antiplatelet therapy; effectiveness; ischemic stroke; outcomes; safety.

Figure 1.

Study flowchart. DAPT, dual antiplatelet therapy; EA, endarterectomy; NIHSS, National Institute of Health Stroke Scale score.

Figure 2.

HR for admission SBP predicting 90-day risk of new ischemic stroke or other vascular events. Light red area around the slope indicates 95% confidence intervals. The SBP value of 124 mm Hg (blue point), where the HR approximated 1, was selected as the cut-off point for patient stratification. HR, hazard ratio; SBP, systolic blood pressure.

Figure 3.

Kaplan–Meier cumulative function of 90-day new ischemic stroke or other vascular events in the weighted population. Estimates and numbers at risk below the curves reflect the weighted pseudo-population. Shaded areas indicate 95% confidence intervals. CI, confidence interval; HR, hazard ratio; SBP, systolic blood pressure.

Figure 4.

Margin plots illustrating the relationship between admission SBP and the probability of 90-day ischemic stroke or new vascular events, analyzed by sex (a) and time to DAPT start (b). Each graph shows the predicted probability of 90-day new ischemic stroke and other vascular events (solid line) and 95% confidence intervals (shade) in a different subgroup. Each model was adjusted for age and sex, when applicable. DAPT, dual antiplatelet therapy; SBP, systolic blood pressure.