Effect of inorganic nitrite vs. placebo on exercise capacity among patients with HFpEF

Researchers for the INDIE-HFpEF clinical trial sought to determine whether inhaled inorganic nitrite improved exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF). For the randomized, crossover trial, 105 patients with HFpEF were randomized to inorganic nitrite or placebo via micronebulizer.

Researchers for the INDIE-HFpEF clinical trial sought to determine whether inhaled inorganic nitrite improved exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF). For the randomized, crossover trial, 105 patients with HFpEF were randomized to inorganic nitrite or placebo via micronebulizer. In each 6-week phase of the study, patients received no study drug for 2 weeks, followed by the study drug or placebo at 46 mg 3 times a day for 1 week followed by 80 mg 3 times a day for 3 weeks. According to the researchers, there was no meaningful difference in mean peak oxygen consumption—the primary endpoint—compared with the placebo phase. Additionally, there was not significant between-treatment phase differences in daily activity levels, functional class, echocardiographic E/e' ratio, or N-terminal fragment of the prohormone brain natriuretic peptide levels. A total of 3 participants experienced worsening heart failure during the nitrite phase, compared with 8 during the placebo phase. The results indicate that "inhaled sodium nitrite, a nitric oxide–providing therapy, did not improve peak aerobic capacity, daily activity levels, quality-of-life scores, or other indicators of clinical status in patients with chronic HFpEF," the researchers said, contrasting with "multiple earlier studies suggesting administration of inorganic nitrite or nitrate may have benefits in HFpEF."