Takeda Pharmaceuticals USA, Inc., 55 Hayden Ave, Lexington, MA, 02420, USA.
Analysis Group, Inc., Boston, MA, USA.
Adv Ther. 2022 Aug;39(8):3845-3856. doi: 10.1007/s12325-022-02198-y. Epub 2022 Jun 11.
Patients with chronic hypoparathyroidism are at increased risk of cardiovascular disease. This study evaluated the risk of developing cardiovascular conditions over a period of 5 years in adult patients with chronic hypoparathyroidism treated with recombinant human parathyroid hormone (1-84), rhPTH(1-84), compared with a historical control cohort of patients not treated with rhPTH(1-84).
This retrospective cohort study comprised patients with chronic hypoparathyroidism treated with rhPTH(1-84) in the REPLACE (NCT00732615), RELAY (NCT01268098), and RACE (NCT01297309) clinical trials, and controls selected from the IBM Explorys electronic medical record database (January 2007-August 2019) who did not receive parathyroid hormone but who had enrollment criteria similar to those for the clinical trials. Cardiovascular outcomes were the first diagnosis of cerebrovascular, coronary artery, peripheral vascular disease, or heart failure during the study period.
We evaluated 113 adult patients with chronic hypoparathyroidism treated with rhPTH(1-84) and 618 control patients who did not receive rhPTH(1-84). Over the 5-year follow-up period, 3.5% of patients (n = 4) in the rhPTH(1-84) cohort had a cardiovascular event compared with 16.3% (n = 101) in the control cohort. Kaplan-Meier analysis demonstrated that patients in the rhPTH(1-84) cohort had lower risk of experiencing a cardiovascular event compared with patients in the control cohort (P = 0.005). Multivariable analyses adjusted for baseline variables showed that patients in the rhPTH(1-84) cohort had 75% lower risk for a cardiovascular event compared with patients in the control cohort (adjusted hazard ratio, 0.25 [95% CI 0.08-0.81]; P = 0.020).
Long-term treatment with rhPTH(1-84) was associated with a lower risk of incident cardiovascular conditions compared with conventional therapy in patients with chronic hypoparathyroidism. Previous studies demonstrated that mineral homeostasis was maintained with lower use of calcium and active vitamin D when rhPTH(1-84) was added to conventional therapy. Future studies are needed to understand whether improved regulation of mineral homeostasis conferred by rhPTH(1-84) may provide long-term cardiovascular benefits to patients with chronic hypoparathyroidism.
患有慢性甲状旁腺功能减退症的患者患心血管疾病的风险增加。本研究评估了在接受重组人甲状旁腺激素（1-84），rhPTH（1-84）治疗的成年慢性甲状旁腺功能减退症患者中，在 5 年内发生心血管疾病的风险，与未接受 rhPTH（1-84）治疗的历史对照队列患者进行比较。
这项回顾性队列研究包括接受 rhPTH（1-84）治疗的慢性甲状旁腺功能减退症患者，这些患者来自于 REPLACE（NCT00732615）、RELAY（NCT01268098）和 RACE（NCT01297309）临床试验，以及从 IBM Explorys 电子病历数据库中选择的对照组患者（2007 年 1 月至 2019 年 8 月），这些患者未接受甲状旁腺激素治疗，但符合临床试验的纳入标准。心血管结局是研究期间首次诊断出的脑血管、冠状动脉、外周血管疾病或心力衰竭。
我们评估了 113 名接受 rhPTH（1-84）治疗的成年慢性甲状旁腺功能减退症患者和 618 名未接受 rhPTH（1-84）治疗的对照组患者。在 5 年的随访期间，rhPTH（1-84）组中有 3.5%（n=4）的患者发生心血管事件，而对照组中有 16.3%（n=101）的患者发生心血管事件。Kaplan-Meier 分析表明，与对照组相比，rhPTH（1-84）组患者发生心血管事件的风险较低（P=0.005）。多变量分析调整了基线变量，结果显示 rhPTH（1-84）组患者发生心血管事件的风险比对照组低 75%（调整后的危险比，0.25[95%CI 0.08-0.81]；P=0.020）。
与慢性甲状旁腺功能减退症患者的传统治疗相比，长期使用 rhPTH（1-84）治疗与心血管疾病发生率较低相关。先前的研究表明，当 rhPTH（1-84）与传统治疗联合使用时，钙和活性维生素 D 的使用量减少，矿物质稳态得以维持。需要进一步的研究来了解 rhPTH（1-84）改善矿物质稳态的调节是否可以为慢性甲状旁腺功能减退症患者带来长期的心血管益处。
