EVOLVE
Trial question
What is the effect of cinacalcet on CVD in patients undergoing dialysis?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
41.0% female
59.0% male
N = 3883
3883 patients (1578 female, 2305 male).
Inclusion criteria: patients with moderate-to-severe secondary hyperparathyroidism (median level of intact PTH, 693 pg/mL) who were undergoing hemodialysis.
Key exclusion criteria: unstable medical condition, parathyroidectomy in the 12 weeks before the date of informed consent, severe concomitant disease, history of seizure within 12 weeks prior to randomization, scheduled date for kidney transplant from a known living donor, anticipated parathyroidectomy within 6 months after randomization, or pregnancy or breast feeding.
Interventions
N=1948 cinacalcet (at a starting dose of 30 mg daily with dose adjustment up to 180 mg daily).
N=1935 placebo (matching placebo).
Primary outcome
Death, MI, hospitalization for unstable angina, heart failure, or a peripheral vascular event
48.2%
49.2%
49.2 %
36.9 %
24.6 %
12.3 %
0.0 %
Cinacalcet
Placebo
No significant
difference ↔
No significant difference in death, MI, hospitalization for unstable angina, HF, or a peripheral vascular event (48.2% vs. 49.2%; HR 0.93, 95% CI 0.85 to 1.02).
Secondary outcomes
No significant difference in CV death (377 vs. 391; HR 0.92, 95% CI 0.8 to 1.07).
No significant difference in adjudicated stroke (115 vs. 102; HR 1.07, 95% CI 0.82 to 1.4).
Safety outcomes
Significant difference in hypocalcemia (12.4% vs. 1.7%) and gastrointestinal adverse events (75.2% vs. 47.9%).
Conclusion
In patients with moderate-to-severe secondary hyperparathyroidism (median level of intact PTH, 693 pg/mL) who were undergoing hemodialysis, cinacalcet was not superior to placebo with respect to death, MI, hospitalization for unstable angina, HF, or a peripheral vascular event.
Reference
EVOLVE Trial Investigators, Chertow GM, Block GA et al. Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. N Engl J Med. 2012 Dec 27;367(26):2482-94.
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