日本昭和大学医学院Tadao Akizawa团队比较了碳酸镧与碳酸钙治疗高磷血症对血液透析慢性肾病患者心血管事件的影响。2021年5月18日，该研究发表在《美国医学会杂志》上。

在接受透析的高磷血症患者中，目前尚不清楚非钙基磷酸盐粘合剂是否比钙基粘合剂能更有效地减少心血管事件。

为了探讨碳酸镧与碳酸钙相比是否能减少血液透析中高磷血症伴血管钙化患者的心血管事件，2011年11月至2018年6月，研究组对日本273家血液透析机构的2374例慢性肾病患者进行了一项盲终点判定的开放标签、随机、平行组临床试验。符合条件的患者有高磷血症和一个或多个血管钙化的危险因素（即，≥65岁，绝经后，糖尿病）。

将患者随机分组，其中1154例接受碳酸镧治疗，1155例接受碳酸钙治疗，维持血清磷酸盐水平在3.5 mg/dL和6.0 mg/dL之间。主要结局是复合心血管事件（心血管死亡、非致命性心肌梗死或中风、不稳定性心绞痛、短暂性脑缺血发作或因心力衰竭或室性心律失常而住院）。次要结局包括总生存率、无继发性甲状旁腺功能亢进生存率、无髋部骨折生存率和不良事件。

2309例接受随机分组的患者中位年龄为69岁，其中40.5%为女性，共有1851人（80.2%）完成了试验。中位随访3.16年后，碳酸镧组1063例患者中有147例发生心血管事件，碳酸钙组1072例患者中有134例，组间差异不显著。两组患者的全因死亡率或髋部骨折率无显著差异。与碳酸钙组相比，碳酸镧组心血管死亡和继发性甲状旁腺功能亢进的风险增加。碳酸镧组发生不良事件282例（25.7%），碳酸钙组发生不良事件259例（23.4%）。

研究结果表明，对于患有高磷血症和至少有一个血管钙化危险因素的血液透析患者，碳酸镧治疗高磷血症与碳酸钙相比，在复合心血管事件方面并没有显著差异。

附：英文原文

Title: 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

Author: Hiroaki Ogata, Masafumi Fukagawa, Hideki Hirakata, Tatsuo Kagimura, Masanori Fukushima, Tadao Akizawa, LANDMARK Investigators and Committees, Masashi Suzuki, Yoshiki Nishizawa, Chikao Yamazaki, Shiro Tanaka, Shuzo Kobayashi, Issei Komuro, Kazuhiko Tsuruya, Hideki Fujii, Hirotaka Komaba, Masatomo Taniguchi, Takeshi Hasegawa, Takayuki Hamano, Masahide Mizobuchi, Takashi Akiba, Ryoichi Ando, Kunitoshi Iseki, Masaaki Inaba, Takatoshi Kakuta, Hitoshi Kato, Hideki Kawanishi, Eriko Kinugasa, Fumihiko Koiwa, Takashi Shigematsu, Tetsuo Shoji, Yoshiharu Tsubakihara, Yoshihiro Tominaga, Masaaki Nakayama, Ichiei Narita, Shinichi Nishi, Kosaku Nitta, Jun Minakuchi, Keitaro Yokoyama, Yuzo Watanabe, Noritomo Itami, Tetsuo Komota, Kenji Yuasa, Akimi Uehata, Ikuo Takahashi, Mikihiko Fujishima, Kazutaka Kukita, Ibuki Yajima, Kanji Shishido, Noriko Toshima, Masato Oroku, Tomoki Yonaha, Koshi Goto, Kazuyuki Maeno, Motoko Tanaka, Tomoko Okuda, Hiroyuki Tamura, Tokihiko Sawada, Senji Okuno, Masaki Fukushima, Takashi Sekiguchi, Kazuyoshi Nakamura, Ryuji Suzuki, Teruo Kowatari, Ikuto Masakane, Minoru Ito, Hirofumi Hashimoto, Hiroaki Ogata, Ryuji Aoyagi, Sumi Hidaka, Jun Mizuguchi, Toshio Shinoda, Kenji Tanaka, Shohei Sawada, Takahiro Kawakami, Masayuki Iyoda

Issue&Volume: 2021/05/18

Abstract:

Importance  Among patients with hyperphosphatemia undergoing dialysis, it is unclear whether non–calcium-based phosphate binders are more effective than calcium-based binders for reducing cardiovascular events.

Objective  To determine whether lanthanum carbonate reduces cardiovascular events compared with calcium carbonate in patients with hyperphosphatemia at risk of vascular calcification undergoing hemodialysis.

Design, Setting, and Participants  Open-label, randomized, parallel-group clinical trial with blinded end point adjudication performed in 2374 patients with chronic kidney disease from 273 hemodialysis facilities in Japan. Eligible patients had hyperphosphatemia and 1 or more risk factors for vascular calcification (ie, ≥65 years, postmenopausal, diabetes). Enrollment occurred from November 2011 to July 2014; follow-up ended June 2018.

Interventions  Patients were randomized to receive either lanthanum carbonate (n=1154) or calcium carbonate (n=1155) and titrated to achieve serum phosphate levels of between 3.5 mg/dL and 6.0 mg/dL.

Main Outcomes and Measures  The primary outcome was a composite cardiovascular event (cardiovascular death, nonfatal myocardial infarction or stroke, unstable angina, transient ischemic attack, or hospitalization for heart failure or ventricular arrhythmia). Secondary outcomes included overall survival, secondary hyperparathyroidism-free survival, hip fracture–free survival, and adverse events.

Results  Among 2309 randomized patients (median age, 69 years; 40.5% women), 1851 (80.2%) completed the trial. After a median follow-up of 3.16 years, cardiovascular events occurred in 147 of 1063 patients in the lanthanum calcium group and 134 of 1072 patients in the calcium carbonate group (incidence rate, 4.80 vs 4.30 per 100 person-years; difference 0.50 per 100 person-years [95% CI, 0.57 to 1.56]; hazard ratio [HR], 1.11 [95%, CI, 0.88 to 1.41], P=.37). There were no significant differences in all-cause death (difference, 0.43 per 100 person-years [95% CI, 0.63 to 1.49]; HR, 1.10 [95% CI, 0.88 to 1.37]; P=.42) or hip fracture (difference, 0.10 per 100 person-years [95% CI, 0.26 to 0.47]; HR, 1.21 [95% CI, 0.62 to 2.35]; P=.58). The lanthanum carbonate group had an increased risk of cardiovascular death (difference, 0.61 per 100 person-years [95% CI, 0.02 to 1.21]; HR, 1.51 [95% CI, 1.01 to 2.27]; P=.045) and secondary hyperparathyroidism (difference, 1.34 [95% CI, 0.49 to 2.19]; HR, 1.62 [95% CI, 1.19 to 2.20]; P=.002). Adverse events occurred in 282 (25.7%) in the lanthanum carbonate group and 259 (23.4%) in the calcium carbonate groups.

Conclusions and Relevance  Among patients undergoing hemodialysis with hyperphosphatemia and at least 1 vascular calcification risk factor, treatment of hyperphosphatemia with lanthanum carbonate compared with calcium carbonate did not result in a significant difference in composite cardiovascular events. However, the event rate was low, and the findings may not apply to patients at higher risk.

DOI: 10.1001/jama.2021.4807

Source: https://jamanetwork.com/journals/jama/article-abstract/2779993