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

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.