How Does Phosphate Binder Type Affect the Heart in Hemodialysis?

Non-calcium-based phosphate binders weren’t any better at reducing cardiovascular events than calcium-based binders in dialysis patients, the LANDMARK trial determined.

In the open-label randomized trial of over 2,300 Japanese patients on hemodialysis, there were no significant differences in composite cardiovascular events between the lanthanum carbonate group versus the calcium carbonate group (HR 1.11, 95% CI 0.88-1.41, P=0.37), reported Hiroaki Ogata, MD, of Showa University Northern Yokohama Hospital in Kanagawa, Japan, and colleagues.

These heart events included cardiovascular death, nonfatal myocardial infarction or stroke, unstable angina, transient ischemic attack, or hospitalization for heart failure or ventricular arrhythmia, the group explained in JAMA.

During the median 3.16-year follow-up period, 147 of 1,063 dialysis patients using lanthanum carbonate experienced cardiovascular events compared with 134 of 1,072 patients in the calcium carbonate group.

This equated to a composite cardiovascular event incident rate of 4.80 per 100 person-years for the lanthanum carbonate group versus 4.30 per 100 person-years for the calcium carbonate group (difference 0.50 per 100 person-years, 95% CI -0.57 to 1.56).

“[T]he event rate was low, and the findings may not apply to patients at higher risk,” Ogata and team pointed out.

However, when breaking down the composite cardiovascular events, the lanthanum carbonate group did see a significantly increased risk specifically for cardiovascular death (HR 1.51, 95% CI 1.01-2.27, P=0.045). This equated to an incidence rate difference of 0.61 per 100 person-years (95% CI 0.02-1.21) compared with the calcium carbonate group.

The only other significant difference seen between the two groups of binders involved secondary hyperparathyroidism — with a 62% higher risk seen in the lanthanum carbonate group (HR 1.62, 95% CI 1.19-2.20, P=0.002).

On the other hand, risk of all-cause death and hip fracture weren’t significantly different between the two groups.

Safety was also similar when comparing binder types: 25.7% of the lanthanum carbonate group and 23.4% of the calcium carbonate group experienced any type of adverse event. Gastrointestinal events were more common in the lanthanum carbonate group versus the calcium carbonate group.

The trial recruited participants with chronic kidney disease from 273 hemodialysis facilities in Japan. Among the 2,374 patients included, all had hyperphosphatemia and at least one other factor for vascular calcification, such as type 2 diabetes, postmenopausal status, or age 65 and older. All had an intact parathyroid hormone level of 240 pg/mL or less and were expected to live at least 1 year. Some exclusion criteria included peritoneal dialysis and contraindications to lanthanum carbonate or calcium carbonate such as prior stroke, heart failure, or ischemic heart disease.

The majority of the cohort were men with type 2 diabetes and a median age of 69. The most common primary cause of end-stage kidney disease was diabetic nephropathy, followed by glomerular disease and hypertension. The median duration of hemodialysis was 4.7 years.

A total of 1,154 dialysis patients received lanthanum carbonate with an initial oral dose of 750 mg/day — three separate doses of 250 mg immediately following meals — or their previously prescribed dose. Doses were then titrated up to a maximum of 2,250 mg/day in order to achieve serum phosphate levels of 3.5 mg/dL to 6.0 mg/dL at the beginning of the first dialysis session each week. Within the lanthanum carbonate group, administration of calcium carbonate was not allowed.

The 1,155 patients assigned to the calcium carbonate group were given an oral dose of 3,000 mg/day — three separate doses of 1,000 mg immediately after meals — or their previously prescribed dose. Sevelamer hydrochloride or another calcium-free phosphate binder could be added if the desired serum phosphate level wasn’t achieved. However, lanthanum carbonate was not allowed for this group.

“The appropriate use of calcium-based phosphate binders has the potential to reduce health care expenditures because of its low cost and high tolerability,” Ogata’s group wrote, adding that this study “demonstrates the need for an RCT [randomized clinical trial] among diverse patient populations to determine whether environmental, ethnic, or racial differences contribute to differences in the effects of lanthanum carbonate vs calcium carbonate.”

They noted that one limitation to this trial was size, as they didn’t achieve the original target for the number of enrolled participants.

These findings were first presented at the American Society of Nephrology’s annual Kidney Week meeting in 2018.