Serelaxin, Drops in SBP, and Poor Outcomes in Patients With Heart Failure

Systolic blood pressure (SBP) drops in patients with acute heart failure and normal to high SBP at hospital admission are associated with worse short- and long-term outcomes. Those drops may be less harmful in patients receiving serelaxin according to a study published in Circulation: Heart Failure.

The post hoc, retrospective analysis investigated whether SBP drops are associated with outcomes in patients treated with serelaxin from 4 clinical trials.

The main inclusion criteria were hospital admission for acute heart failure, age ≥18 years, subjective dyspnea, pulmonary congestion on chest radiograph, elevated NT-proBNP (N-terminal pro-B-type natriuretic peptide; >2000 pg/mL), and SBP between 125 and 180 mm Hg measured twice while bedridden.

Patients were randomly assigned in a 1:1 fashion to either a 48-hour infusion of serelaxin 30 μg per kilogram per day or placebo. In 1 trial, allocation was 1:2 in favor of serelaxin vs usual care.

Outcomes were all-cause, 180-day mortality and a composite short-term outcome of all-cause mortality, worsening heart failure, or hospital readmission for heart failure through day 14.

The pooled serelaxin cohort included 11,226 patients. They were mean aged 73±11 years, 40% were women, and their mean baseline SBP was 143±17 mm Hg at randomization.

A total of 2559 patients had an SBP drop, of whom 69% had an absolute systolic value lower than 100 mm Hg and 31% had a systolic drop of 40 mm Hg from baseline.

Patients who had an SBP drop during hospitalization had a higher cumulative incidence of 180-day mortality vs those without an SBP drop (11% [9%-12%] vs 9% [8%-0%]; P =.01) and a higher cumulative incidence of the composite outcome (11% [10%-12%] vs 9% [8%-10%]; P =.007).

Multivariable Cox regression showed that an SBP drop was associated with short-term composite outcome (adjusted hazard ratio [aHR], 1.29 [1.13-1.49]; P =.0003) and 180-day all-cause mortality (aHR, 1.21 [1.05-1.39]; P =.009).

According to the researchers, for the short-term composite outcome, the importance of SBP drop was different with and without the serelaxin (P interaction =.003), which suggests that serelaxin attenuates the relationship between an SBP drop and increased mortality and the composite outcome.

No significant association was found among patients (n=6064) treated with serelaxin (aHR, 1.18 [0.97-1.42]; P =.10). However, in usual care or placebo patients (n=5141), an SBP-drop was associated with a 46% increased risk of the composite outcome (cumulative incidence 14% [15%-13%] vs 9% [9%-10%]; aHR, 1.46 [1.19-1.79]; P =.0003).

In an analysis for the interaction with serelaxin for the 2 components of the SBP drop, SBP lower than 100 mm Hg and serelaxin interacted (P interaction =.002), suggesting that serelaxin attenuates the relationship between SBP lower than 100 mm Hg and the composite outcome. This interaction was not observed in a decrease from baseline of 40 mm Hg (P interaction =.32).

A 6-hour SBP of 130 to 140 mm Hg was associated with the best short- and long-term prognosis.

Study limitations include its retrospective and observational design, as the investigators could not determine a causal relationship between SBP drop and outcomes. In addition, patients with significant comorbidity and those with SBP lower than 125 mm Hg and higher than 180 mm Hg were excluded.

“The observations from the reported analysis suggest that blood pressure lowering in patients hospitalized for acute heart failure with baseline [SBPs] between 125 mm Hg and 180 mm Hg may need to be tempered, taking care to avoid lowering [SBP] below 100 mm Hg, particularly in patients with baseline systolic blood pressure [less than or equal to] 140 mm Hg,” the researchers noted.

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Grand J, Miger K, Sajadieh A, et al. Blood pressure drops during hospitalization for acute heart failure treated with serelaxin: a patient-level analysis of 4 randomized controlled trials. Circ Heart Fail. Published online February 21, 2022. doi: 10.1161/CIRCHEARTFAILURE.121.009199