ESC 2014 Report: Intravenous supplementation improves iron deficiency in heart failure

by Bruce Sylvester: Two intravenous doses of an iron supplement appears to cause heart failure patients with iron deficiency to achieve significant improvements in functional capacity, quality of life and reduced risk of hospitalization for worsening heart failure.

Researchers presented findings from the CONFIRM-HF (Ferric CarboxymaltOse evaluatioN on perFormance in patients with IRon deficiency in coMbination with chronic Heart Failure) on August 30, 2014 at ESC 2014. The study appeared simultaneously in the European Heart Journal.

The investigators enrolled 304 stable, symptomatic heart failure patients.

All subjects had been diagnosed with iron deficiency, a serum ferritin level of less than 100 ng/mL, or between 100 and 300 ng/mL if transferrin saturation [TSAT] was less than 20%.

The researchers randomized the subjects to intravenous iron (n=152), given as ferric carboxymaltose solution (FCM), or a normal saline placebo (n=152), for 52 weeks.

Dosings took place at baseline, 6, 12, 24, and 36 weeks.

.Among the FCM cohort subjects, median total dose was 1500 mg of iron during the 52 weeks, ranging from 500 to 3500 mg.

At each dosing, more than 75% of the FCM subjects required a maximum of two injections of FCM to maintain the iron parameters.

All subjects completed a six-minute walk test (6MWT) at baseline. The primary endpoint of the study was improvement in the 6MWT at week 24.

Compared to placebo-treated subjects, FCM-treated subjects achieved a significant increase in distance completed during the 6MWT 33 extra meters at week 24 (p=0.002), 42 extra meters at week 36, and 36 extra meters at week 52 (both p<0.001).

“The magnitude of the treatment effect of FCM on the 6MWT distance, is robust and clinically meaningful,”  investigator Dr. Piotr Ponikowski of the Medical University in Wrocław, Poland. “In previous interventional studies, such beneficial effects have only been seen with cardiac resynchronisation therapy.”

Notably, improvement in the 6MWT distance appeared among all patient subgroups, including those with and without anemia.

Findings also indicated improvement in other measures of functional status and quality of life among FCM-treated subjects compared to placebo-treated subjects.

After week 12, the FCM-treated subjects achieved a significant benefit in Patient Global Assessment compared with placebo (p= 0.035 at week 12, p=0.047 at week 24 and p<0.001 at weeks 36 and 52). There was a similar relative improvement between the cohorts in New York Heart Association class (p= 0.004 at week 24 and p< 0.001 at weeks 36 and 52).

Fatigue scores improved significantly among the FCM-treated subjects compared to placebo-treated subjects. The same was true for quality of life scores on both the Kansas City Cardiomyopathy Questionnaire [KCCQ] and European Quality of Life 5D [EQ-5D]  questionnaire.
Treatment with FCM resulted in a significant 61% reduction in the risk of hospitalization due to worsening heart failure (hazard ratio [HR] 0.39; p=0.009), compared to placebo.

“Hospitalizations due to heart failure are an economic burden for society, resulting in poor outcomes and impaired quality of life for patients.  There is evident need for their prevention. In this context the results of CONFIRM-HF are of particular interest. Among recently introduced pharmacological therapies only ivabradine has demonstrated such results,” said  Ponikowski.
Mortality was similar in both cohorts, suggesting that longer follow-up may be needed to test this outcome.

Adverse events were mild, and appeared at similar rates in both groups.

“Current ESC guidelines for managing heart failure patients recognize iron deficiency as a common and clinically relevant comorbidity which should always be tested for,” concluded Ponikowski. “However at the same time, there is a relatively weak recommendation to manage iron deficiency in such patients, mainly because of a paucity of evidence confirming the benefits of iron repletion. For a stronger recommendation of iron depletion as a valid therapeutic target in heart failure, well-designed and controlled studies with adequate follow-up are needed. CONFIRM-HF was designed and executed with this goal. We believe that the results of this trial will be most important when it comes to defining the role of iron repletion for heart failure iron deficient patients in the next ESC Heart Failure guidelines in 2016.”