Iron Replacement Has No Impact on Disease Severity, Quality of Life in PAH

Idiopathic pulmonary arterial hypertension (PAH) is associated with iron deficiency, which is in turn associated with worse functional capacity and survival in PAH; however, iron repletion by infusion provided no significant clinical benefit, according to a new study published in Annals of the American Thoracic Society.

Guidelines suggest iron replacement in the management of pulmonary hypertension, but “there remain concerns about the safety of iron supplementation in idiopathic and heritable PAH and its impact on pulmonary vascular resistance, cardiac function, and exercise capacity remain to be defined,” the authors explained.

They reported on 2 randomized, double-blind studies investigating the safety and efficacy of iron replacement in patients with idiopathic or heritable PAH who have iron deficiency without anemia.

One study recruited 39 patients in 4 specialists centers in London, Cambridge, and Sheffield, United Kingdom; and Giessen, Germany. They were randomized 1:1 to a single infusion of ferric carboxymaltose or saline given over 15 minutes. There was cross over after 12 weeks.

The iron treatment increased ferritin from 17 ug/L at baseline to 146 ug/L at 12 weeks in the group of patients treated with ferric carboxymaltose initially. In the patients treated initially by placebo who crossed over, ferritin increased from 14 ug/L to 134.5 ug/L from weeks 12 to 24.

Soluble transferrin receptor levels decreased in both groups, but treatment had no significant effect on the secondary end points or on endurance time measured on cardiopulmonary exercise testing.

The second study recruited 17 patients from Fu Wai Hospital in Beijing. They were randomized to a single infusion of iron dextran or saline administered over 4 to 6 hours. Again, there was cross over after 12 weeks.

Patients treated with iron dextran had increased serum ferritin levels, but treatment did not impact pulmonary vascular resistance (PVR), which was the primary outcome. There was also no significant effect on any secondary end points.

The researchers pooled the patient-level data from the 2 studies to investigate the effect on PVR, 6-minute walk distance, peak oxygen consumption (VO₂), and VO₂ at metabolic threshold on incremental cardiopulmonary exercise testing. There was no beneficial signal and iron replacement had no effect on cardiac function at 12 weeks.

“Iron replacement in the absence of overt anaemia has no clinically significant impact on markers of disease severity or quality of life at 12 weeks,” the authors concluded. “Patients with iron deficiency should not be denied iron replacement at the discretion of the physician but this report should temper the expectation of therapeutic benefit from iron replacement in PAH patients with iron deficiency in the absence of anaemia.”

Reference

Howard LSGE, He J, Watson GMJ, et al. Supplementation with iron in pulmonary arterial hypertension: two randomized crossover trials. Ann Am Thorac Soc. Published online March 18, 2021. doi:10.1513/AnnalsATS.202009-1131OC