Abstract
Chronic hypoparathyroidism is associated with an increased risk of cardiovascular (CV) complications. This study investigated CV events over a period of up to 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 who did not receive rhPTH(1–84). The rhPTH(1–84)-treated patient cohort was derived from the NCT00732615 (REPLACE), NCT01268098 (RELAY), and NCT01297309 (RACE) clinical trials. A control cohort of adult patients who did not receive rhPTH(1–84) or rhPTH(1–34) was selected from the US Explorys electronic medical record database (Jan 2007−Aug 2019) using selection criteria similar to the enrollment criteria used in the trials. Index date was the day after initiation of treatment for the rhPTH(1–84) cohort and the day after the first calcitriol prescription for the control cohort. The primary outcome was the risk of a composite CV event (defined as any event of cerebrovascular disease, coronary artery disease, heart failure, or peripheral vascular disease) in the rhPTH(1–84) cohort compared with the control cohort through 5 years post-index. Patients with a CV event at baseline were excluded from the analysis. Risk of a CV event was assessed in a Kaplan-Meier analysis and a Cox proportional hazards model adjusted for demographic characteristics, baseline clinical conditions, and baseline serum calcium levels. The analysis included 113 patients in the rhPTH(1–84) cohort and 618 patients in the control cohort. Patients in the rhPTH(1–84) cohort, compared with the control cohort, were younger (mean ± SD age, 47.8±12.0 vs 51.0±16.8 years; P<0.05), a higher proportion were White (94.7% vs 81.9%; P<0.01), and fewer had acute manifestations of hypoparathyroidism before the index date (22.1% vs 69.6%; P<0.001). In a Kaplan-Meier analysis, rhPTH(1–84)-treated patients had a significantly reduced risk of developing a CV event compared with patients in the control cohort (P<0.01); 3.5% of rhPTH(1–84)-treated patients and 16.3% of control cohort patients developed a CV event over the 5-year follow-up period. The adjusted hazard ratio for developing a CV event associated with rhPTH(1–84) treatment vs no rhPTH(1–84) treatment was 0.23 (95% CI, 0.07−0.74; P<0.05). This analysis is limited by differences in patient management under predefined clinical trial protocols for the rhPTH(1–84) cohort vs real-world clinical practice for the control cohort. Over 5 years, patients with chronic hypoparathyroidism treated with rhPTH(1–84) in clinical trials had a significantly reduced risk of CV events compared with a control cohort of patients who did not receive rhPTH(1–84). Further research is needed to better understand the mechanism underlying the association between chronic hypoparathyroidism and risk of developing a CV event.
Use of historical control data for assessing treatment effects in clinical trials