Nitrate therapy linked to less exercise in heart failure

Isosorbide mononitrate therapy for patients with heart failure and preserved ejection fraction may actually be associated with lower levels of daily activity and does not appear to achieve significant improvements in quality of life or exercise capacity, compared with placebo.

In a double-blind crossover trial in 110 patients who were prescribed escalating doses of isosorbide mononitrate over a period of 6 weeks and then switched, those patients treated with the highest dose of 120 mg once daily showed a nonsignificant trend (P = .06) toward lower daily activity and hours of activity per day, compared with those given placebo.

According to data presented at the American Heart Association scientific sessions and published simultaneously Nov. 8 in the New England Journal of Medicine, researchers observed a decrease in average daily accelerometer units with increasing doses of isosorbide mononitrate, but not with placebo (N Engl J Med. 2015 Nov 8 [doi: 10.1056/NEJMoa1510774]).

They also noted a nonsignificant decrease in quality of life scores, N-terminal probrain natriuretic peptide, and blood pressure with isosorbide mononitrate, as well as a greater number of discontinuations and adverse events.

Although nitrates are commonly prescribed for symptom relief in heart failure, the authors said, the pathophysiology of heart failure with preserved ejection fraction may be responsible for the observed lack of improvement in exercise tolerance and daily activity.

“Increased ventricular systolic and vascular stiffness, autonomic dysfunction, chronotropic incompetence, and altered baroreflex sensitivity are common and may limit the hemodynamic benefit of nitrates,” wrote Dr. Margaret M. Redfield of the Mayo Clinic, Rochester, Minn., and her coauthors.

The National Heart, Lung, and Blood Institute supported the study. Several authors reported grants, fees, royalties and consultancies from private industry, including a patent relating to natriuretic peptide.

Isosorbide mononitrate therapy for patients with heart failure and preserved ejection fraction may actually be associated with lower levels of daily activity and does not appear to achieve significant improvements in quality of life or exercise capacity, compared with placebo.

In a double-blind crossover trial in 110 patients who were prescribed escalating doses of isosorbide mononitrate over a period of 6 weeks and then switched, those patients treated with the highest dose of 120 mg once daily showed a nonsignificant trend (P = .06) toward lower daily activity and hours of activity per day, compared with those given placebo.

According to data presented at the American Heart Association scientific sessions and published simultaneously Nov. 8 in the New England Journal of Medicine, researchers observed a decrease in average daily accelerometer units with increasing doses of isosorbide mononitrate, but not with placebo (N Engl J Med. 2015 Nov 8 [doi: 10.1056/NEJMoa1510774]).

They also noted a nonsignificant decrease in quality of life scores, N-terminal probrain natriuretic peptide, and blood pressure with isosorbide mononitrate, as well as a greater number of discontinuations and adverse events.

Although nitrates are commonly prescribed for symptom relief in heart failure, the authors said, the pathophysiology of heart failure with preserved ejection fraction may be responsible for the observed lack of improvement in exercise tolerance and daily activity.

“Increased ventricular systolic and vascular stiffness, autonomic dysfunction, chronotropic incompetence, and altered baroreflex sensitivity are common and may limit the hemodynamic benefit of nitrates,” wrote Dr. Margaret M. Redfield of the Mayo Clinic, Rochester, Minn., and her coauthors.

The National Heart, Lung, and Blood Institute supported the study. Several authors reported grants, fees, royalties and consultancies from private industry, including a patent relating to natriuretic peptide.

Isosorbide mononitrate therapy for patients with heart failure and preserved ejection fraction may actually be associated with lower levels of daily activity and does not appear to achieve significant improvements in quality of life or exercise capacity, compared with placebo.

In a double-blind crossover trial in 110 patients who were prescribed escalating doses of isosorbide mononitrate over a period of 6 weeks and then switched, those patients treated with the highest dose of 120 mg once daily showed a nonsignificant trend (P = .06) toward lower daily activity and hours of activity per day, compared with those given placebo.

According to data presented at the American Heart Association scientific sessions and published simultaneously Nov. 8 in the New England Journal of Medicine, researchers observed a decrease in average daily accelerometer units with increasing doses of isosorbide mononitrate, but not with placebo (N Engl J Med. 2015 Nov 8 [doi: 10.1056/NEJMoa1510774]).

They also noted a nonsignificant decrease in quality of life scores, N-terminal probrain natriuretic peptide, and blood pressure with isosorbide mononitrate, as well as a greater number of discontinuations and adverse events.

Although nitrates are commonly prescribed for symptom relief in heart failure, the authors said, the pathophysiology of heart failure with preserved ejection fraction may be responsible for the observed lack of improvement in exercise tolerance and daily activity.

“Increased ventricular systolic and vascular stiffness, autonomic dysfunction, chronotropic incompetence, and altered baroreflex sensitivity are common and may limit the hemodynamic benefit of nitrates,” wrote Dr. Margaret M. Redfield of the Mayo Clinic, Rochester, Minn., and her coauthors.

The National Heart, Lung, and Blood Institute supported the study. Several authors reported grants, fees, royalties and consultancies from private industry, including a patent relating to natriuretic peptide.