Supplementation with Iron in Pulmonary Arterial Hypertension. Two Randomized Crossover Trials

Ann Am Thorac Soc. 2021 Jun;18(6):981-988. doi: 10.1513/AnnalsATS.202009-1131OC.


Rationale: Iron deficiency, in the absence of anemia, is common in patients with idiopathic and heritable pulmonary arterial hypertension (PAH) and is associated with a worse clinical outcome. Oral iron absorption may be impeded by elevated circulating hepcidin concentrations. The safety and benefit of parenteral iron replacement in this patient population is unclear. Objectives: To evaluate the safety and efficacy of parenteral iron replacement in PAH. Methods: In two randomized, double-blind, placebo-controlled 12-week crossover studies, 39 patients in Europe received a single infusion of ferric carboxymaltose (Ferinject) (1,000 mg or 15 mg/kg if weight <66.7 kg) or saline as placebo, and 17 patients in China received iron dextran (Cosmofer) (20 mg iron/kg body weight) or saline placebo. All patients had idiopathic or heritable PAH and iron deficiency at entry as defined by a serum ferritin <37 μg/L or iron <10.3 μmol/L or transferrin saturations <16.4%. Results: Both iron treatments were well tolerated and improved iron status. Analyzed separately and combined, there was no effect on any measure of exercise capacity (using cardiopulmonary exercise testing or 6-minute walk test) or cardiopulmonary hemodynamics, as assessed by right heart catheterization, cardiac magnetic resonance, or plasma NT-proBNP (N-terminal-pro hormone brain natriuretic peptide) at 12 weeks. Conclusions: Iron repletion by administration of a slow-release iron preparation as a single infusion to patients with PAH with iron deficiency without overt anemia was well tolerated but provided no significant clinical benefit at 12 weeks. Clinical trial registered with (NCT01447628).

Keywords: exercise capacity; ferric carboxymaltose; iron; iron dextran; pulmonary arterial hypertension.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia, Iron-Deficiency* / drug therapy
  • Cross-Over Studies
  • Dietary Supplements
  • Double-Blind Method
  • Familial Primary Pulmonary Hypertension
  • Humans
  • Iron
  • Pulmonary Arterial Hypertension*
  • Treatment Outcome


  • Iron

Associated data