Lower Risk of Cardiovascular Events in Adult Patients with Chronic Hypoparathyroidism Treated with rhPTH(1–84): A Retrospective Cohort Study

INTRODUCTION: 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). METHODS: 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. RESULTS: 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). CONCLUSION: 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12325-022-02198-y.