The risk of cardiovascular death in patients with chronic kidney disease is increased by a factor of ten in comparison with the general population. While a host of factors including chronic inflammation, increased oxidative stress and endothelial dysfunction contribute to this risk, disorders of mineral metabolism, including secondary hyperparathyroidism, are thought to contribute by promoting extraskeletal (including vascular) calcification. Cinacalcet is a calcimimetic agent that reduces levels of parathormone, calcium and phosphorous and in this large randomised controlled trial was assessed to reduce the risk of death or nonfatal cardiovascular events in patients on haemodialysis.
A total of 3883 patients with moderate-to-severe secondary hyperparathyroidism who were undergoing haemodialysis were randomised to receive either cinacalcet or placebo along with conventional therapy, including phosphate binders, vitamin D sterols, or both. Patients were followed for up to 64 months with the primary end point a composite of time until death, myocardial infarction, hospitalization for unstable angina, heart failure, or a peripheral vascular event. In an intention to treat analysis there was no benefit demonstrated with cinacalcet with the primary composite end point reached in 938 of 1948 patients (48.2%) in the cinacalcet group and 952 of 1935 patients (49.2%) in the placebo group (HR 0.93; 95% CI, 0.85 to 1.02; P=0.11) with no differences demonstrable in any of the components of the composite end-point between the two groups either. The results of the study however were clouded by a lower than anticipated event rate, a high dropout rate in both groups and almost 20% of the placebo group using commercially available cinacalcet, with adjusted analyses suggesting a nominally significant benefit for cinacalcet in reducing cardiovascular events (p=0.02).
In an intention-to-treat analysis of this large randomised trial, cinacalcet did not significantly reduce the risk of death or major cardiovascular events in patients undergoing renal dialysis. However, problems with the trial protocol suggest further study is necessary.
- Chertow GM, Block GA, Correa-Rotter R, Drüeke TB, Floege J, Goodman WG, Herzog CA, Kubo Y, London GM, Mahaffey KW, Mix TC, Moe SM, Trotman ML, Wheeler DC, Parfrey PS. Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. N Engl J Med. 2012 Dec 27;367(26):2482-94.