Mineralocorticoid Receptor Antagonists Unlikely to Induce Hypotension in HFrEF

By Marilynn Larkin

January 18, 2020

NEW YORK (Reuters Health) - Patients with heart failure with reduced ejection fraction (HFrEF) can be treated with mineralocorticoid receptor antagonists (MRAs) and are unlikely to develop hypotension as a result, an analysis of two large randomized trials reveals.

"These extremely valuable drugs (MRAs) are underused in patients with heart failure, particularly in the USA and Canada," Dr. John JV McMurray of the University of Glasgow told Reuters Health by email. "One of the reasons given is that doctors believe that MRAs might cause a significant fall in blood pressure, and patients with heart failure often have a low blood pressure."

"However," he said, "this is clearly not the case...and hopefully, with this information, we have removed one of the barriers to the use of this life-saving treatment in patients with heart failure."

Dr. McMurray and colleagues analyzed the effect of MRA therapy in HFrEF patients participating in two placebo-controlled trials - one with spironolactone and one with eplerenone. In both trials, the starting dose of the study drug was 25 mg once daily. Spironolactone could be increased to 50 mg after eight weeks, whereas eplerenone was increased to 50 mg daily after four weeks, absent hyperkalemia or other intolerance.

Of note, neither trial had a lower blood pressure exclusion criterion.

As reported in JACC: Heart Failure, 4,396 patients (mean age, 67; 24% women; 84% white) were included in the analysis, including 2,214 randomized to placebo and 2,182 to an MRA.

There were 702 patients with a baseline systolic blood pressure (SBP) of 105 mmHg or less; 870 with an SBP between 105 to 115; 960 with an SBP >115 to 125; 823 with an SBP of >125 to 135; and 1,041 with an SBP >135.

Patients with a lower SBP were younger, more often male, had a worse NYHA functional class status and a lower median left ventricular ejection fraction. However, they were also less likely to have a history of hypertension, coronary heart disease or diabetes. They had worse renal function and a slightly lower potassium than patients with a higher SBP.

The mean change in SBP from baseline to one month was -0.5 mmHg in the placebo groups and -2.4 mmHg in the MRA groups. The mean SBP change from baseline to six months was +1.4 with placebo and - 1.2 mmHg with an MRA.

All outcomes were reduced by MRA therapy overall, with consistent effects across SBP categories. For example, HRs for all-cause mortality were 0.72 overall; 0.72 for an SBP of 105 mmHg or less; 0.78 for >105 to 115; 0.71 for >115 to 125; 0.79 for >125 to 135; and 0. 67 for >135.

Hypotension was infrequent and not more common with an MRA than with placebo overall (4.6% vs. 3.9%) or in any SBP category.

Summing up, the authors state, "Contrary to what is found in hypertension, MRAs do not have a substantial SBP-lowering effect in HFrEF...MRA treatment had little effect on SBP in HFrEF and the clinical benefits were not modified by baseline SBP. MRA treatment infrequently caused hypotension, even when the baseline SBP was low. The treatment-discontinuation rate was similar with MRA and placebo. Low SBP is not a reason to withhold MRA therapy in HFrEF."

Dr. Garrie Haas, medical director of heart failure at The Ohio State University Wexner Medical Center in Columbus, told Reuters Health he agrees with the findings. "In general, MRAs should not be withheld for fear of inducing hypotension in patients with HFrEF. The risk / benefit in this situation (symptomatic HFrEF) markedly favors the use of the drug. This has certainly been my experience in HF clinical practice."

"The primary adverse effect that should be monitored for when initiating treatment with MRA remains labs - serum potassium level and renal function," he said. "Otherwise, these drugs are safe to use and clearly have an important effect on HF outcomes (e.g., mortality). Their effect on reducing blood pressure in the HFrEF population is minimal (and) the risk of high potassium levels is the same with both drugs."

SOURCE: http://bit.ly/2TstXfz JACC: Heart Failure, online January 8, 2020.