Drug doesn't significantly lower risk of major heart problems in dialysis patients

In one of the largest and longest trials involving patients with kidney failure, a study led by an international team of researchers found that cinacalcet — a drug commonly prescribed to patients with kidney failure and a disturbance of bone and mineral metabolism known as secondary hyperparathyroidism — does not significantly reduce the risk of death or major cardiovascular events.

The results of the trial known as EVOLVE, which enrolled nearly 4,000 kidney patients from several continents and stretched over five years, were mixed, researchers said.

"The results of the EVOLVE trial suggest that cinacalcet favorably alters bone and mineral metabolism, and could result in improved health and longevity for patients with end-stage renal disease," said the study's lead author, Glenn Chertow, MD, professor of medicine and chief of nephrology at the Stanford University School of Medicine. "But the trial was not definitive in determining cardiovascular benefits because so many patients discontinued taking the study drug."

Researchers did say the trial results showed possible cardiovascular benefits when certain factors were taken into account, such as an imbalance in age between study participants who were treated with cinacalcet and those who received a placebo. Those who received the drug were on average a year older; age is a major risk factor for cardiovascular disease.

"The trial is not definitive in its results; however, recognizing some of the limitations — such as the high dropout rate — it is suggestive of a cardiovascular health benefit," said co-author Geoffrey Block, MD, medical director of Denver Nephrology.

The study will be published online Nov. 3 in the New England Journal of Medicine and will also be presented at the American Society of Nephrology annual meeting in San Diego the same day.

Patients on kidney dialysis are among the most frail and chronically ill, with high mortality and hospitalization rates. This makes recruitment and retention of such patients in clinical trials particularly challenging, the study stated.

Earlier studies suggested that cinacalcet, one of several drugs used to treat secondary hyperparathyroidism, may also help to prevent or ameliorate cardiovascular disease. Cinacalcet is manufactured by Amgen Inc., a biotechnology firm located in Thousand Oaks, Calif., which sponsored the EVOLVE trial.

Because secondary hyperparathyroidism and associated disorders are linked with death, fractures and cardiovascular disease, physicians have prescribed the drug in the hopes of preventing cardiovascular events in patients undergoing dialysis. Its side effects include nausea and gastrointestinal distress.

"Secondary hyperparathyroidism develops when the kidneys are unable to maintain the balance of certain minerals, including phosphorus and calcium," Chertow said. "In this setting, the bones do not mineralize normally, and blood vessels and other tissues can become calcified."