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MRAs, Blood Pressure, and Outcomes in HFrEF
Study Questions:
What is the effect of mineralocorticoid receptor antagonists (MRAs) on systolic blood pressure (SBP) and outcomes in patients with heart failure with reduced ejection fraction (HFrEF)?
Methods:
Two major randomized placebo-controlled trials, RALES (Randomized Aldactone Evaluation Study) and EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure), used MRA therapy (spironolactone and eplerenone) in patients with HFrEF. Both databases were merged for analyses in this study and 4,396 patients were analyzed. Patients were divided into five baseline SBP categories: ≤105 mm Hg, >105 to ≤115 mm Hg, >115 to ≤125 mm Hg, >125 to ≤135 mm Hg, and >135 mm Hg. The primary outcome was the composite of cardiovascular death or HF hospitalization. All-cause death, occurrence of investigator-reported hypotension, elevation of serum potassium, elevation of creatinine, and the rate of permanent study drug discontinuation for any reasons other than death were also examined.
Results:
A total of 2,214 patients were randomized to placebo and 2,182 patients to an MRA. Patients with a lower SBP were younger and more often male, and had a lower median left ventricular EF and worse New York Heart Association functional class. Overall, the mean change in SBP from baseline to 1 month was -0.5 (standard deviation [SD], 15.9) mm Hg in the placebo group and -2.4 (SD, 16.3) mm Hg in the MRA group. This resulted in a between-treatment difference of 1.9 (95% confidence interval, 0.9-2.0; p < 0.001) mm Hg. Compared with placebo, MRA therapy reduced the risk of the primary composite outcome (cardiovascular death or HF hospitalization). The benefit of MRA therapy was consistent across all SBP categories. 4.2% of patients experienced hypotension: 3.9% in the placebo group and 4.6% in the MRA group. Elevation of creatinine and potassium were more common in the MRA than in the placebo group. 19.9% of patients permanently discontinued study treatment for reasons other than death. The rate of discontinuation between placebo and MRA did not differ across SBP categories.
Conclusions:
MRA treatment has little effect on BP in patients with HFrEF. MRA treatment did not worsen hypotension, even when the SBP baseline was low. The rate of discontinuation between placebo and MRA did not differ.
Perspective:
MRA therapy should continue to be used as guideline-directed medical therapy in patients with HFrEF. When hypotension arises, consider causes other than MRA therapy prior to discontinuation.
Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure
Keywords: Blood Pressure, Blood Pressure Determination, Creatinine, Heart Failure, Hypotension, Mineralocorticoid Receptor Antagonists, Potassium, Spironolactone, Stroke Volume, Ventricular Dysfunction, Left
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