Iron Infusion Aids Exercise, Overall Health of PAH Patients Lacking Mineral
Infusion with Ferinject (ferric carboxymaltose) safely treated people with pulmonary arterial hypertension (PAH) and iron deficiency, easing disease symptoms, improving exercise capacity, and lowering their number of hospital visits over a period of 18 months, a long-term study reported.
Ferinject, as this treatment for iron deficiency anemia is known in Europe, is available in the U.S. under the brand name Injectafer. It is approved for people who fail to respond sufficiently to oral iron supplements, or are unable to take such supplements.
Iron is essential to the body for functions that include the production of hemoglobin — the protein in red blood cells responsible for carrying oxygen to tissues. Iron deficiency is common to PAH patients — estimated to be found in 43–60% of these people — affecting their ability to exercise and increasing the frequency and severity of disease symptoms.
Oral iron supplements are reported to be of limited benefit to people with PAH and iron deficiency. But a few short-term studies have shown that a single intravenous infusion of Ferinject can improve the ability of muscle cells to carry oxygen, aiding their exercise capacity and quality of life.
Pulmonary hypertension (PH) guidelines and recommendations suggest iron supplementation be considered for PAH patients. However, the long-term effects of a supplement delivered intravenously are unknown.
A team of researchers in Germany assessed the impact and feasibility of a Ferinject infusion (500 to 1,000 mg) given to 58 iron deficient PAH patients as a supplement between December 2010 and October 2018, and then followed for 18 months (1.5 years). Their data were compared with a matched group of 59 PAH patients without iron deficiency (a control group), also followed for 18 months.
Patient data included exercise capacity, as shown in the 6-minute walk distance (6MWD, a test of functional capacity), health indicators, their World Health Organization functional classification (WHO-FC), and heart function.
The mean age of the 117 total patients was 60.9, and most (64.15%) were women. All were on stable PAH therapies, and exams were conducted three, six, 12, and 18 months.
Iron deficiency was defined as blood ferritin (a blood protein that stores iron) lower than 100 micrograms per liter (mcg/L), or a blood ferritin level of 100 to 300 mcg/L with a transferrin saturation (an indicator of iron status) lower than 20%, in the absence of significant inflammation.
Findings showed that a Ferinject infusion improved all markers of iron status (iron, ferritin, and transferrin saturation) during the 18 months of observation.
Fourteen patients needed a second infusion after an average of 9.6 months. Iron levels dropped repeatedly in four of them, and they required a maximum of three iron infusions throughout the study.
Iron replacement improved exercise capacity at six and 18 months after an iron infusion. This was seen by an increase in the 6-minute walk distance from 377.5 meters at baseline (pretreatment or study’s start) to 412.5 meters after six months and 401 meters after 18 months. In contrast, the distance walked by patients in the control group slightly deteriorated over time.
“The restoration of iron status in the intervention group was associated with an improvement of exercise capacity and symptom burden within the first 6 months and throughout the observation period,” the researcher wrote, later adding that the “magnitude of changes in the 6MWD upon correction of ID [iron deficiency] was similar to improvements reached by PAH-targeted drugs in several randomized controlled trials.”
The percentage of patients listed as WHO-FC I or II, characterized by no symptoms at rest but possible shortness of breath in normal activities, increased from 38% at the study’s start to 55% at 18 months. Among control group patients, the proportion in this WHO functional class dropped slightly, from 52% at baseline to 43% at 18 months, indicating a worsening in disease status.
No changes were found in heart function after iron supplementation. However, the rate of hospital visits was lower in patients given a Ferinject infusion. During the 12-month prior to this treatment, 22.4% of iron-deficient patients (13 people) had been hospitalized due to PAH, with a total of 16 hospital visits. Twelve months after iron replacement, four or 6.9% of these people had been hospitalized for PAH, with a total five number of hospital visits.
“Our data suggest a reduction of PAH-associated hospitalizations upon [ferric carboxymaltose] treatment,” the researchers wrote.
Furthermore, the ESC/ERS (European Society of Cardiology/European Respiratory Society) risk status — an important indicator of likely PAH prognosis or outcomes — also improved. Specifically, the proportion of patients in the iron supplement group with low-risk status increased from 24.1% at baseline to 31% at 18 months, a “remarkable shift,” the researchers reported.
“Because the risk status is known to predict mortality rates in PAH, bringing the patient into the low-risk category is considered as an important treatment goal in PAH,” they wrote.
Ferinject was generally well tolerated and safe, with no serious adverse events reported.
“In addition to targeted therapy, correction of ID by parenteral iron supplementation with [ferric carboxymaltose] appears feasible and safe, has sustained effects on iron status, and may improve the clinical status and hospitalization rates in patients with PAH,” the researchers concluded.
The team noted, however, that “larger controlled studies are required to confirm this finding.”