Cinacalcet use and the risk of cardiovascular events, fractures and mortality in chronic kidney disease patients with secondary hyperparathyroidism

Marie Evans,Juan-Jesus Carrero,Shona Methven,Fergus J Caskey,Peter Barany,Alessandro Gasparini,Margaret T May,Stephanie Macneill,Kate Birnie

doi:10.1038/s41598-018-20552-5

Abstract

With the aim to expand the randomized controlled trial evidence of cinacalcet treatment to the unselected, general chronic kidney disease (CKD) population we analysed a large inception cohort of CKD patients in the region of Stockholm, Sweden 2006–2012 (both non-dialysis, dialysis and transplanted) with evidence of secondary hyperparathyroidism (SHPT). We used marginal structural models to account for both confounding by indication and time-dependent confounding. Over 37 months, 435/3,526 (12%) initiated cinacalcet de novo. Before cinacalcet initiation, parathyroid hormone (PTH) had increased progressively to a median of 636ng/L. After cinacalcet initiation, PTH declined, as did serum calcium and phosphate. In total, 42% of patients experienced a fatal/non-fatal cardiovascular event, 32% died and 9% had a new fracture. The unadjusted cardiovascular odds ratio (OR) associated with cinacalcet treatment was 1.01 (95% confidence interval: 0.83, 1.22). In the fully weighted model, the cardiovascular odds was lower in cinacalcet treated patients (OR 0.67: 0.48, 0.93). The adjusted ORs for all-cause mortality and for fractures were 0.79 (0.56, 1.11) and 1.08 (0.59, 1.98) respectively. Our study suggests cinacalcet treatment improves biochemical abnormalities in the wider CKD population, and adds real-world support that treating SHPT with cinacalcet may have beneficial effects on cardiovascular outcomes.

Highlights

Chronic kidney disease (CKD) is a common disease with a life-time risk in the United States as high as 59%1
In this study we aimed to analyse if treatment with cinacalcet in chronic kidney disease (CKD) patients with secondary hyperparathyroidism (SHPT) was associated with improved cardiovascular outcomes, all-cause mortality or fractures compared with non-treatment
No effect modification was seen for age strata, sex or dialysis/transplantation status at baseline (Web Appendix). In this analysis of referred CKD patients in the region of Stockholm with secondary hyperparathyroidism, we found that initiation of cinacalcet was associated with a lower odds of cardiovascular events compared with no use

Summary

Introduction

Chronic kidney disease (CKD) is a common disease with a life-time risk in the United States as high as 59%1. The increased levels of parathyroid hormone (PTH), often seen in patients with CKD, has been associated with the increased risk of cardiovascular events, fractures and mortality[3]. In those with end-stage kidney disease, secondary hyperparathyroidism (SHPT) accelerates vascular calcification and subclinical atherosclerosis[4,5] and further lead to hyper-dynamic bone disease and osteitis fibrosis cystica (renal osteodystrophy). In this study we aimed to analyse if treatment with cinacalcet in CKD patients with SHPT was associated with improved cardiovascular outcomes, all-cause mortality or fractures compared with non-treatment. We undertook this study in a complete healthcare utilization cohort in Stockholm, Sweden using MSMs19 to provide less biased estimates by controlling for baseline confounding by indication and time-dependent confounding

Objectives

Methods

Results

Conclusion