ESC Congress 2026 Abstract · Oct 26, 2026
Non-linear associations between systolic blood pressure and clinical outcomes in atrial fibrillation and net clinical benefit of oral anticoagulants: a dose-response meta-analysis
By Shahmohamadi E, Elliott A, Middeldorp M et al.
Background: Hypertension has the highest attributable risk for AF and is also an important determinant of associated stroke and bleeding risks. Clinical data are limited regarding blood pressure targets and how hypertension modulates the therapeutic impact of direct oral anticoagulants (DOAC). Purpose: We aimed to characterize the dose-response relationship between baseline systolic blood pressure (SBP) and the risk of ischemic stroke, mortality, and intracranial hemorrhage and net-clinical benefit (NCB) of DOAC and warfarin at preventing them Method: A systematic search of PubMed, EMBASE, and Cochrane databases was conducted to identify studies that reported clinical outcomes in patients with AF stratified by baseline SBP categories. We performed a dose-response meta-analysis to evaluate the association between SBP and clinical outcomes. Restricted cubic splines with three knots were used to model potential non-linear relationships, while linear trends were assessed for outcomes without significant non-linearity. Within-study correlation was accounted for using the Greenland and Longnecker method. NCB was calculated by weighing the prevention of ischemic events against the risk of intracranial hemorrhage while a weight of 1.5 was applied to hemorrhagic events based on existing literature. Subgroup interaction analyses were performed across SBP groups and NCB quantified as the number of clinical events prevented per 100 patient-years. Results: 11 studies (n=281,224) were included. The relationship between SBP and ischemic stroke was J-shaped. Compared to a reference of 110 mmHg, stroke risk remained stable until 135 mmHg, then increased significantly with a relative risk of (RR) 1.11 (95% CI: 1.01–1.17) at 145 mmHg and 1.16 (95% CI: 1.07–1.33) at 160 mmHg. All-cause mortality exhibited a significant U-shaped association (P_non-linearity <0.05), with a nadir at 135 mmHg. In contrast, intracranial hemorrhage demonstrated a significant linear association; each 10 mmHg increase in SBP was associated with a 27% higher risk (RR 1.27; 95% CI: 1.12–1.44). The net clinical benefit of DOAC therapy was greatest and statistically significant in the high SBP group (>140 mmHg), with an estimated prevention of 6.54 weighted events per 100 patients (95%CI: 3.29–9.78, p<0.0001). In contrast, the NCB did not reach statistical significance in the low (1.17, p=0.37) or medium (-0.48, p=0.71) SBP categories. Conclusion: We found a U-shaped relationship between mortality and baseline SBP in patients with AF, with the lowest risk observed at 135 mmHg. We also observed a significant escalation in both ischemic risk and bleeding beyond this threshold. These findings suggest that 135 mmHg represents an optimal SBP target for this population. Also, this meta-analysis confirms that the NCB of DOACs over warfarin simultaneously increases, and is amplified in patients with uncontrolled hypertension (SBP>140 mmHg) at baseline.Figure1Net Clinal Benefit