Key result
DOACs yield greatest net clinical benefit over warfarin at elevated SBP despite ~11% higher stroke risk.
Why the study?
Clinical data are limited regarding blood pressure targets in patients with AF and how hypertension modulates the therapeutic impact and net clinical benefit of direct oral anticoagulants versus warfarin.
Does baseline systolic blood pressure modulate the risk of ischemic stroke, mortality, and intracranial hemorrhage, and the net clinical benefit of direct oral anticoagulants over warfarin in patients with atrial fibrillation?
Meta-Analysis (n=281,224)
Does baseline systolic blood pressure modulate the risk of ischemic stroke, mortality, and intracranial hemorrhage, and the net clinical benefit of direct oral anticoagulants over warfarin in patients with atrial fibrillation?
In patients with atrial fibrillation, a baseline systolic blood pressure of 135 mmHg is associated with the lowest mortality and represents a threshold for escalating stroke risk, while the net clinical benefit of DOACs over warfarin is significantly amplified in those with uncontrolled hypertension (>140 mmHg).
Supports targeting SBP ≤135 mmHg in AF to minimize mortality and stroke; extends evidence quantifying greatest DOAC net benefit above 140 mmHg.
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
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Shahmohamadi et al. (2026) conducted a meta-analysis in Atrial fibrillation (n=281,224). Baseline systolic blood pressure and direct oral anticoagulants (DOAC) vs. Reference SBP of 110 mmHg and warfarin was evaluated on Ischemic stroke, all-cause mortality, intracranial hemorrhage, and net clinical benefit (RR 1.11 at 145 mmHg; RR 1.16 at 160 mmHg (for ischemic stroke vs 110 mmHg), 95% CI 1.01-1.17, p=<0.0001). Baseline SBP >135 mmHg increased stroke and mortality risks in AF, while DOACs vs warfarin yielded the greatest net clinical benefit at SBP >140 mmHg (6.54 events prevented/100 patients, p<0.0001).
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