Systolic Blood Pressure and Pulse Pressure in Heart Failure: Pooled Participant-Level Analysis of 4 Trials

Background: Hypertension is common in patients with heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), and current guidelines recommend treating systolic blood pressure (SBP) to a target <130 mm Hg. However, data supporting treatment to this target are limited. Additionally, pulse pressure (PP), a marker of aortic stiffness, has been associated with increased risk of cardiovascular events, but its prognostic impact in HFpEF has not been extensively studied.

Objectives: This study aimed to explore the impact of baseline SBP and PP on cardiovascular outcomes in patients with HFmrEF or HFpEF.

Methods: The I-PRESERVE (Irbesartan in Heart Failure With Preserved Ejection Fraction), TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist)-Americas, PARAGON-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin-Receptor Blocker Global Outcomes in HF With Preserved Ejection Fraction), and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trials were global, randomized clinical trials testing irbesartan, spironolactone, sacubitril/valsartan, and dapagliflozin, respectively, against either a placebo or an active comparator (valsartan, in PARAGON-HF), in patients with heart failure and a left ventricular ejection fraction ≥40% (in DELIVER) or ≥45% (in the other trials). The relationship between continuous baseline SBP and PP, and the primary endpoint (first heart failure hospitalization or cardiovascular death) was analyzed with restricted cubic splines. We further evaluated the prognostic impact of SBP categories (<120, 120-129, 130-139, and ≥140 mm Hg) and PP quartiles on the primary endpoint.

Results: A total of 16,950 patients (mean age 71 ± 9 years; 49% male; mean SBP 131 ± 15 mm Hg; mean PP 55 ± 14 mm Hg) were included. The relationship between SBP and the primary endpoint was J-shaped, with the lowest risk at 120 to 130 mm Hg. A similar pattern was found for PP, with the lowest risk at 50 to 60 mm Hg. The highest SBP category (reference: 120-129 mm Hg) and PP quartile (reference: 46-54 mm Hg) were associated with a higher risk of the primary outcome (HR: 1.22; 95% CI: 1.10-1.34 and HR: 1.22; 95% CI: 1.11-1.34, respectively). Higher PP was associated with greater cardiovascular risk, regardless of SBP.

Conclusions: Our analysis of a large pooled dataset from 4 clinical trials, including >16,900 patients with HFmrEF/HFpEF, indicates a J-shaped relationship between both SBP and PP and cardiovascular risk. The lowest risk was observed at SBP levels between 120 and 130 mm Hg and PP values between 50 and 60 mm Hg (I-PRESERVE [Irbesartan in Heart Failure With Preserved Systolic Function], NCT00095238; TOPCAT [Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist], NCT00094302; PARAGON-HF [Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction], NCT01920711; DELIVER [Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure], NCT03619213).