Effects of pharmacological blood pressure lowering in heart failure with mildly reduced or preserved ejection fraction: a meta-analysis

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BACKGROUND: The role of blood pressure (BP) lowering in patients with heart failure (HF) with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) remains uncertain, and it is unclear to what extent the existing benefits of therapies are mediated by BP reduction. METHODS AND RESULTS: A systematic review and meta-analysis of randomised clinical trials was conducted, comparing any BP lowering treatment to placebo, usual care or another drug class in patients with HFmrEF/HFpEF. The primary endpoint was a composite of cardiovascular death and HF hospitalisation. Data were pooled using a random effects meta-analysis and meta-regression with inverse variance weighting expressed as a risk ratio (RR) and its 95% CI. 18 studies were identified totalling 39 452 patients. Pharmacological BP lowering led to a significant reduction in the primary composite endpoint (RR 0.86, 95% CI 0.83 to 0.89; p≤0.001), but there were significant differences between drug classes (p value=0.018), with evidence of benefit with sodium-glucose cotransporter 2 inhibitor, mineralocorticoid receptor antagonist, angiotensin-receptor neprilysin inhibitor and glucagon-like peptide-1 receptor agonists but not other drug classes. Meta-regressions found no significant association between the degree of BP reduction and treatment effects (coefficient slope=-0.0125, p=0.304). Similarly, pharmacological BP lowering was associated with a reduction in HF hospitalisations (RR 0.83, 95% CI 0.79 to 0.86; p≤0.001), but treatment effects were not related to degree of BP reduction (coefficient slope=-0.0121, p=0.528). CONCLUSION: In patients with HFmrEF/HFpEF, there was no significant association between pharmacological BP lowering and clinical outcomes, suggesting that BP lowering alone is unlikely to explain all the benefits observed with the use of recently established HF therapies. PROSPERO REGISTRATION NUMBER: CRD42025631539.

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