Novel Inhaled Tx Found to Be Ineffective for Patients With Heart Failure

The trial enrolled 105 patients who had HFpEF causing shortness of breath and fatigue with ordinary or mild physical activity.

Treatment with inhaled inorganic nitrite did not improve exercise capacity, daily activity levels, severity of symptoms or quality of life (QoL) in patients with heart failure with preserved ejection fraction (HFpEF), according to findings presented at the ACC.18 Scientific Sessions & Expo.

Inorganic nitrite, a novel nitric oxide-providing agent, is preferentially activated during exercise. Preliminary studies have suggested that inhalation of inorganic nitrite could potentially improve exercise capacity by reducing pressure in the heart.

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In this multicenter, double-blind, 12-week crossover study (INDIE-HFpEF Trial), researchers investigated whether inhaled nitrite could improve exercise capacity (peak VO2) in HFpEF patients. Study patients (N=105) underwent a 2-week baseline/washout during each 6-week phase of the crossover. They then received nitrite or placebo via a portable micronebulizer device at 46mg 3 times daily for 1 week followed by 80mg 3 times daily for 3 weeks. 

The primary endpoint was change in peak VO2 after 4 weeks of treatment; daily activity levels assessed by accelerometry, functional class, QoL, cardiac filling pressures assessed by echocardiography and NT-proBNP levels, other exercise indices, and safety and tolerability were secondary endpoints.

The results showed no significant differences for any primary or secondary endpoints. In the nitrite treatment arm, there was no effect on peak VO2 vs placebo group. Likewise, no significant between-group differences were seen in daily activity levels, health-related QoL, symptom severity classification, echocardiographic and exercise measures, or NT-proBNP levels. 

Possible factors that may have affected the trial outcomes include: patients having to use the nebulizer 3 times daily for 10 minutes each, insufficient exposure to medication with a 4-week treatment duration, and no requirement to increase patient activity levels.

Lead author, Barry A. Borlaug, MD, professor of medicine at Mayo Clinic in Rochester, MN, stated, “We are disappointed that this treatment strategy failed to live up to the promise it had shown in preliminary studies. We need to redouble our efforts to find an effective approach to treating this patient population, which represents a huge unmet public health need.” 

Another study is currently underway to evaluate whether HFpEF patients who receive both exercise training and nitrite medication perform better than patients who receive exercise training and placebo.


Borlaug B, Anstrom K, Lewis G, et al. Inorganic Nitrite Delivery to Improve Exercise Capacity in Heart Failure with Preserved Ejection Fraction: The INDIE Trial. Presented at: ACC.18 Scientific Sessions & Expo. March 10–12, 2018; Orlando, FL. Abstract #405-10.