Adding Iron May Help Maintain Exercise Capacity in Heart Failure


CME NUGGETS

ED SUSMAN

Mr. Susman is a freelance medical writer based in Florida, USA. He travels worldwide to report from medical conferences, writing regularly for wire services, internet websites, and medical journals such as the Journal of the National Cancer Institute and AIDS.

For comments, edwardsusman@cs.com


NEW ORLEANS, Louisiana – The addition of iron to the medication regimen of people struggling with advanced heart failure may help maintain some exercise capacity – but a lot of the benefit depends upon how the iron is delivered, researchers reported here at the 2016 scientific sessions of the American Heart Association.

In separate studies, researchers reported that intravenous iron – administered three times – maintained exercise capacity, but daily iron supplements failed to do any better than placebo.

In the so-called EFFECT trial, intravenous treatment with ferric carboxymaltose in heart failure patients with iron deficiency maintained exercise capacity as measure by peak oxygen consumption (VO2) after six months of treatment, reported Dirk van Veldhuisen, MD, PhD, professor and chief of cardiology at the University Medical Center, Groningen, the Netherlands.

Dr. Veldhuisen, in his late-breaker presentation, suggested the study results “confirm and extend the results of previous studies that treatment with ferric carboxymaltose improves exercise capacity and symptoms.”

On the other hand, researchers treating patients with oral iron agents had a different outcome. In the so-called IRONOUT study, Gregory Lewis, MD, medical director of the cardiology intensive care unit at Massachusetts General Hospital/Harvard Medical School, Boston, found that treatment with oral iron polysaccharide did not improve exercise capacity in heart failure patients when compared with placebo after 16 weeks of treatment.

“High dose oral iron minimally repleted iron stores and did not improve peak VO2 in patients with iron deficiency and heart failure with reduced ejection fraction,” Dr. Lewis said.

In the EFFECT trial, 88 patients diagnosed with heart failure and iron deficiency were randomly assigned to receive ferric carboxymaltose at a dose of at least 100 micrograms/L at the start of the trial and then at week 6 and week 12 of the 24 week study. They were compared with 85 patients who receive standard of care therapy – but without iron supplementation.

The patients were about 63 years old, and about 20-25 percent were women. Their left ventricular ejection fraction was about 32 percent.

At six months, the exercise capacity of the patients treated with intravenous iron was basically unchanged from baseline, but those who received standard of care therapy has a men decline in VO2 capacity of about 1.2 mL/kg/min. That difference was statistically significant, Dr. Veldhuisen said in his oral presentation (P=0.02).

He said the treatment was well-tolerated.

For IRONOUT, Dr. Lewis and colleagues assigned 111 patients to oral iron at a dose of 150 mg twice a day and also assigned 150 patients to placebo. About 40 percent of the patients were women and the mean age of the cohort was 63. Their men left ventricular ejection fraction was 25 percent.

At 16 weeks, there was no appreciable difference in VO2, nor was there improvement in a wide variety of secondary measures including the six-minute walk test, mean response time of quality of life surveys, Dr. Lewis reported in the late-breaker oral session.

In commenting on the studies, James Udelson, MD, chief of cardiology at Tufts Medical Center, Boston, said, “We know that a substantial number of patients with heart failure have iron deficiency and that creates a lot of co-morbid problems, including problems with oxygen delivery and oxygen utilization. There has been a lot of attention in smaller trials in trying to replete iron to see if that can have a favorable effect in patients.

“In EFFECT, the intravenous therapy achieved iron repletion and allowed people to remain stable in their exercise capacity compared to a slight deterioration in the standard of care group. They also saw favorable changes in the patient quality of life assessment.

“IRONOUT investigators took the approach of oral iron repletion with the idea that might be easier for patients, but results were entirely neutral. It did not appear that the patients were very iron repleted after the therapy. We don’t know if that was a compliance issue or an absorption problem.

“Since they weren’t able to achieve the goal of iron repletion, the neutral results are not surprising,” Dr. Udelson said.

He said that the results do not necessarily provide a mandate for iron repletion in clinical practice. “I think we need to know more about an adverse cardiovascular hospitalization observe in the EFFECT study to determine if it is a true signal. What we have learned is that whether treatment is oral or intravenous, you have to find a way to replete the iron. This is not the end of the story. This is promising.’’

“The IRONOUT study is very important,” said Stefan Anker, MD, PhD, professor of innovative clinical trials at the University of Gottingen, Germany. “Medicine is about things you do and things you shouldn’t do. And this study really tells us that oral iron for patients with heart failure is of no use for symptom improvement, exercise capacity improvement or any other benefits.

“The investigators have to be congratulated,” he said, “because they tried to find out why it didn’t work. And it didn’t work because the iron was simply not take up by the body. There seems to be a blockage that is mediated biochemically in heart failure patients for taking up iron, and so when iron does not get into the body, you simply cannot expect any benefits.”

Adding Iron May Help Maintain Exercise Capacity in Heart Failure 2C-section and obese kids

Women who are obese when they get pregnant and have Cesarian section deliveries are almost three times more likely of having an obese child by age five as children of normal weight women who deliver vaginally.

The obese women who have C-section deliveries are 2.8 times more likely (P<0.01) to have an obese child at age 5, and women who are obese at the time they become pregnant and deliver vaginally are 1.8 times more likely (P<0.01) to have an obese child at age five, said Noel Mueller, PhD, MPH, assistant professor of epidemiology the Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.

Dr. Mueller said that the children of normal weight women who have Cesarian deliveries have a elevated risk of 10 percent to 20 percent of having an obese child at five years of age, but that difference was not statistically significantly different than the children of normal weight women who deliver vaginally.

“We think that the reason for the difference may be due to the beneficial microbes found in the birth canal that newborns are exposed to during a vaginal birth,” Dr. Mueller said. “We suspect that these microbes may benefit a child’s health, including enhancing metabolism and training the immune system.”

“We need more studies to determine whether exposing Cesarean-delivered newborns to vaginal microbes at birth can reduce their future risk of metabolic disorders such as obesity.”

Researchers analyzed data on 1,441 full-term deliveries from the Boston Birth Cohort. The cohort includes about 1,500 pairs of mothers and their children. Among the study group, 57 percent of the women who gave birth by Cesarean were obese and 53 percent of those who delivered vaginally were obese. Mueller said that the researchers found – as had previous researchers – that women who were overweight had children who were overweight; and they also confirmed that children born through C-section tended to be overweight by age five.

“What we also found was that the association between these risk factors seemed to be additive in such a way that women who were obese and delivered by C-section, delivered children who had about a three-fold greater odds of having obesity at age five compared to women who were normal weight and delivered vaginally,” Dr. Mueller said.

Among the vaginal deliveries, 506 women were normal weight; 251 women were overweight and 204 women were obese. Among the women delivered through C-section, 177 were normal weight, 145 of the women were overweight and 158 of the women were obese.The women having vaginal deliveries were somewhat younger than those women having c-Section; the women having c-sections were more likely to have low educational levels; the gestational weight gain was greater across the board in women who had C-sections, and the birth weight of the children of mothers who had C-sections was 70 to 100 grams greater when compared to vaginal deliveries.

Mueller suggested that program that would argue against unnecessary C-sections might be able to reduce the intergenerational association with obesity.

December 2016 Health and Lifestyle

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