Using a non-calcium instead of a calcium-based phosphate binder may not reduce cardiovascular events in patients with hyperphosphatemia undergoing hemodialysis, according to new study findings published in JAMA.

In the LANDMARK trial (NCT01578200), investigators randomly assigned 2309 patients from 273 hemodialysis facilities in Japan to treatment with lanthanum carbonate or calcium carbonate, with doses titrated to achieve serum phosphate levels of 3.5 to 6.0 mg/dL. All patients had hyperphosphatemia and 1 or more risk factors for vascular calcification, such as age older than 65 years, menopause, or diabetes. After a median 3.16 years, cardiovascular events occurred in 4.80 vs 4.30 per 100 person-years in the lanthanum vs calcium carbonate group, respectively, a nonsignificant difference, Hiroaki Ogata, MD, of Showa University Northern Yokohama Hospital in Kanagawa, Japan, and colleagues reported. This primary composite outcome included cardiovascular death, nonfatal myocardial infarction or stroke, unstable angina, transient ischemic attack, or hospitalization for heart failure or ventricular arrhythmia.

With respect to secondary outcomes, the lanthanum carbonate group had significant 51% and 34% increased risks for cardiovascular death and secondary hyperparathyroidism, respectively, the investigators noted. Risks for all-cause death and hip fracture did not differ significantly.

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Adverse events occurred in 25.7% of the lanthanum carbonate group and 23.4% of the calcium carbonate group. Hypercalcemia (serum calcium exceeding 10 mg/dL) was more prevalent in the calcium carbonate group. The median dose of calcium carbonate was approximately 1500 mg/d, which is lower than in some previous trials. Patients were allowed to take calcium-free phosphate binders other than lanthanum carbonate, active vitamin D, cinacalcet, and higher dialysate calcium.

“This trial showed that the lanthanum carbonate-treated group did not have reduced cardiovascular events and all-cause death, compared with the calcium carbonate-treated group, among patients undergoing hemodialysis at cardiovascular risk,” Dr Ogata’s team stated. “However, it remains unknown whether other calcium-free phosphate binders, including sevelamer or iron-based phosphate binders, are more effective than calcium-based phosphate binders in improving clinical outcomes.”

The investigators cautioned that the cardiovascular event rates were low, and the findings may not apply to patients at higher cardiovascular risk. Whether the trial findings can be generalized to non-Japanese populations is also uncertain.

According to Dr Ogata’s team, the results appear to support Kidney Disease Improving Global Outcomes (KDIGO) guidelines on the use of moderately dosed calcium-based binders in patients on hemodialysis at lesser cardiovascular risk.

Disclosure: This research was supported by Bayer Yakuhin Ltd. Please see the original reference for a full list of disclosures.


Ogata H, Fukagawa M, Hirakata H, et al. Effect of treating hyperphosphatemia with lanthanum carbonate vs calcium carbonate on cardiovascular events in patients with chronic kidney disease undergoing hemodialysis: The LANDMARK randomized clinical trial. JAMA. 2021;325(19):1946-1954. doi:10.1001/jama.2021.4807