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NEAT-HFpEF: Isosorbide mononitrate offers insignificant benefit in patients with HFpEF
ORLANDO, Fla. — Isosorbide mononitrate did not improve activity level, exercise capacity or quality of life of patients with HF with preserved ejection fraction, according to results from the NEAT-HFpEF study.
Nitrates are commonly prescribed to boost activity tolerance in people with HF with preserved ejection fraction (HFpEF), so investigators conducted a double blind crossover study to compare the effect of isosorbide mononitrate and placebo on daily activity in those patients, Margaret M. Redfield, MD, said during a press conference at the American Heart Association Scientific Sessions.
Margaret M. Redfield
“The hemodynamic effects of nitrates might attenuate pulmonary congestion with exertion and improve exercise capacity,” she said. “However, patients with HFpEF might be at increased risk for nitrate-induced hypotension or other side effects.”
Redfield, from Mayo Clinic, and colleagues randomized 110 patients with HFpEF to a 6-week dose-escalation regimen of isosorbide mononitrate 30 mg/day to 60 mg/day to 120 mg/day or placebo. At the end of the 6-week period, the placebo group switched to the isosorbide mononitrate regimen for 6 weeks and vice versa.
The primary endpoint was daily activity level as determined by patient-worn accelerometers (KXUS9-2050, Kionix) based on average daily accelerometer units when the 120-mg/day dose of isosorbide mononitrate was in effect.
Secondary endpoints included hours of daily activity during the 120-mg/day phase, daily accelerometer units during all three isosorbide mononitrate dosage phases, quality-of-life scores, 6-minute walk distance and N-terminal pro-brain natriuretic peptide levels.
Redfield and colleagues found that the 120-mg/day phase of isosorbide mononitrate was associated with a trend toward lower daily activity compared with placebo (381 accelerometer units; 95% CI, 780 to 17; P = .06).
In addition, during the 120-mg/day phase of isosorbide mononitrate, patients had fewer hours of activity per day compared with those assigned placebo (0.3 hours; 95% CI, 0.55 to 0.05; P = .02), Redfield said.
They also found that during all phases of the isosorbide mononitrate regimen, daily activity was lower in the isosorbide mononitrate group compared with the placebo group (439 accelerometer units; 95% CI, isosorbide mononitrate 792 to 86; P = .02).
In fact, Redfield said, activity levels decreased with increasing dosage of isosorbide mononitrate, a pattern that was not true for placebo.
The researchers found no difference between the groups in quality-of-life measures (Kansas City Cardiomyopathy Questionnaire, P = .16; Minnesota Living with Heart Failure Questionnaire, P = .37), 6-minute walk scores (treatment difference, 0.57 m; 95% CI, 9.63 to 10.78; P = .91) or NT-proBNP levels (treatment difference, 53 pg/ml; 95% CI, 33 to 138; P = .22).
“As compared to placebo, isosorbide mononitrate decreased daily activity levels and did not improve exercise capacity, quality-of-life scores or NT-proBNP levels in patients with HFpEF,” Redfield said. “We conclude that these data do not support use of long-acting nitrates for symptom relief in HFpEF.”
The findings were simultaneously published in the New England Journal of Medicine. – by Erik Swain
References:
Redfield MM, et al. LBCT 1: Failure is Not an Option: New Drugs and Systems of Care. Presented at: American Heart Association Scientific Sessions; Nov. 7-11, 2015; Orlando, Fla.
Redfield MM, et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1510774.
Disclosures: The study was funded by the NHLBI. Redfield reports receiving grant support from the NHLBI and personal fees from Eli Lilly, the Heart Failure Society of America, the NIH and Merck.
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These findings indicate just how challenging the HFpEF syndrome is; often, things that we all “know” are going to work, don’t work. But you have to test them. It’s disappointing to have a negative trial, but it’s one more piece of the puzzle.
What we know is that nitrates relieve angina, and in patients with HF with reduced ejection fraction, they frequently relieve congestion and can improve symptoms. But I think we have better drugs to use.
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We know little about how to treat this group of patients. What we’ve done traditionally is to treat them as we do patients with HFrEF. For many, we have used isosorbide mononitrates. This study demonstrates to us in a very well-done manner that this is not a therapy that overall has improved quality of life or outcomes in this patient population, so we should probably stop that medication in our patients.