Clinical

High-dose IV iron regimen does not adversely affect incidence of CV events

David Wheeler 2018
David C. Wheeler

SAN DIEGO — The PIVOTAL Trial has shown in patients undergoing hemodialysis, that the use of higher-dose IV iron does reduce erythropoiesis-stimulating agent dose requirements but at the same time, does not increase toxicity or affect mortality or the incidence of nonfatal CV events, according to one of the trial researchers.

“We know that when we use high doses of erythropoiesis-stimulating agents to treat renal anemia that we may induce toxicities in our patients and the outcomes of trials of ESAs have actually shown that high doses of ESAs are associated with an increased risk of cardiovascular events and all-cause mortality,” said David C. Wheeler, MD, who said he was presenting on behalf of Iain C. Macdougall, MD, and the PIVOTAL Study Group.

He said that “one trick” nephrologists use is to give iron with the ESA “so that you can reduce the dose of ESA, and the iron augments the erythropoietic effect of the erythropoiesis-stimulating agents.”

As the optimal amount of iron is unknown, the PIVOTAL (Proactive IV Iron Therapy in Haemodialysis Patients) Trial was started. It is a multicenter, open-label, blinded endpoint, controlled trial, Wheeler said here at ASN Kidney Week 2018.

Wheeler said they screened 2,589 patients who were new to hemodialysis (0 to 12 months), and those who had “a ferritin level of less than 400 µg/L and TSAT of less than 30%” were randomized to a proactive iron regimen or a reactive iron regimen.

In the proactive iron regimen, patients received 400 mg per month and this was withheld only if the ferritin level rose above 700 µg/L or the TSAT was greater than 40%. In the reactive, low-dose iron regimen, patients were only given iron if the ferritin level was less than 200 µg/L or the TSAT was less than 20%.

The ESA dosage was at the discretion of the investigators, Wheeler said. Patients were followed up monthly.

The primary endpoint was a composite of all-cause mortality and nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure or death, he said noting the trial ran for 4.4 years, with a mean follow-up of 2.1 years.

The mean cumulative dose was 3.8 g in the proactive arm and was 1.8 g in the reactive arm. The mean monthly dose was also different.

“That was reflected in increases in serum ferritin in the proactive group – a sharp rise in serum ferritin in the first year of the study” that stabilized to a mean of approximately 600 µg/L. In the reactive arm, the serum ferritin remained low (around 150 to 200 µg/L). He said this was statistically significant.

The ESA dose in the proactive arm was lower than the ESA dose in the reactive arm, Wheeler said.

Researchers found noninferiority between both iron doses, he said.

Also, superiority did not reach statistical significance.

Safety was a concern given that “high doses of intravenous iron might promote safety issues, such as vascular access thrombosis or infection,” Wheeler said.

No difference was found in vascular access thrombosis or all-cause hospitalization, including hospitalization for infection.

“In these patients who were in their first year of starting hemodialysis, our proactive high-dose regimen compared to the reactive low-dose regimen didn’t adversely affect mortality [and] didn’t increase the incidence of cardiovascular events,” he said. “It reduced the ESA requirements in these patients and that may be good if ESAs promote cardiovascular events and reduced the transfusion.”

The proactive high-dose regimen did not increase the risk of infection or hospitalization and “that was certainly a surprise to me,” he said. – by Joan-Marie Stiglich, ELS

 

Reference:

Macdougall IC, et al. FR-OR143. Presented at: ASN Kidney Week; Oct. 23-28, 2018; San Diego.

 

Disclosure: This study was funded by Kidney Research UK and Vifor Fresenius Medical Care Renal Pharma Ltd according to Wheeler.

David Wheeler 2018
David C. Wheeler

SAN DIEGO — The PIVOTAL Trial has shown in patients undergoing hemodialysis, that the use of higher-dose IV iron does reduce erythropoiesis-stimulating agent dose requirements but at the same time, does not increase toxicity or affect mortality or the incidence of nonfatal CV events, according to one of the trial researchers.

“We know that when we use high doses of erythropoiesis-stimulating agents to treat renal anemia that we may induce toxicities in our patients and the outcomes of trials of ESAs have actually shown that high doses of ESAs are associated with an increased risk of cardiovascular events and all-cause mortality,” said David C. Wheeler, MD, who said he was presenting on behalf of Iain C. Macdougall, MD, and the PIVOTAL Study Group.

He said that “one trick” nephrologists use is to give iron with the ESA “so that you can reduce the dose of ESA, and the iron augments the erythropoietic effect of the erythropoiesis-stimulating agents.”

As the optimal amount of iron is unknown, the PIVOTAL (Proactive IV Iron Therapy in Haemodialysis Patients) Trial was started. It is a multicenter, open-label, blinded endpoint, controlled trial, Wheeler said here at ASN Kidney Week 2018.

Wheeler said they screened 2,589 patients who were new to hemodialysis (0 to 12 months), and those who had “a ferritin level of less than 400 µg/L and TSAT of less than 30%” were randomized to a proactive iron regimen or a reactive iron regimen.

In the proactive iron regimen, patients received 400 mg per month and this was withheld only if the ferritin level rose above 700 µg/L or the TSAT was greater than 40%. In the reactive, low-dose iron regimen, patients were only given iron if the ferritin level was less than 200 µg/L or the TSAT was less than 20%.

The ESA dosage was at the discretion of the investigators, Wheeler said. Patients were followed up monthly.

The primary endpoint was a composite of all-cause mortality and nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure or death, he said noting the trial ran for 4.4 years, with a mean follow-up of 2.1 years.

The mean cumulative dose was 3.8 g in the proactive arm and was 1.8 g in the reactive arm. The mean monthly dose was also different.

“That was reflected in increases in serum ferritin in the proactive group – a sharp rise in serum ferritin in the first year of the study” that stabilized to a mean of approximately 600 µg/L. In the reactive arm, the serum ferritin remained low (around 150 to 200 µg/L). He said this was statistically significant.

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The ESA dose in the proactive arm was lower than the ESA dose in the reactive arm, Wheeler said.

Researchers found noninferiority between both iron doses, he said.

Also, superiority did not reach statistical significance.

Safety was a concern given that “high doses of intravenous iron might promote safety issues, such as vascular access thrombosis or infection,” Wheeler said.

No difference was found in vascular access thrombosis or all-cause hospitalization, including hospitalization for infection.

“In these patients who were in their first year of starting hemodialysis, our proactive high-dose regimen compared to the reactive low-dose regimen didn’t adversely affect mortality [and] didn’t increase the incidence of cardiovascular events,” he said. “It reduced the ESA requirements in these patients and that may be good if ESAs promote cardiovascular events and reduced the transfusion.”

The proactive high-dose regimen did not increase the risk of infection or hospitalization and “that was certainly a surprise to me,” he said. – by Joan-Marie Stiglich, ELS

 

Reference:

Macdougall IC, et al. FR-OR143. Presented at: ASN Kidney Week; Oct. 23-28, 2018; San Diego.

 

Disclosure: This study was funded by Kidney Research UK and Vifor Fresenius Medical Care Renal Pharma Ltd according to Wheeler.

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