Patients with
end-stage renal disease often have derangements in
calcium and
phosphorus homeostasis and resultant
secondary hyperparathyroidism (sHPT), which may contribute to the high prevalence of arterial stiffness and
hypertension. We conducted a secondary analysis of the Evaluation of
Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) trial, in which patients receiving
hemodialysis with sHPT were randomly assigned to receive
cinacalcet or placebo. We sought to examine whether the effect of
cinacalcet on death and major cardiovascular events was modified by baseline pulse pressure as a marker of arterial stiffness, and whether
cinacalcet yielded any effects on blood pressure. As reported previously, an unadjusted intention-to-treat analysis failed to conclude that randomization to
cinacalcet reduces the risk of the primary composite end point (all-cause mortality or non-fatal
myocardial infarction,
heart failure, hospitalization for
unstable angina or peripheral vascular event). However, after prespecified adjustment for baseline characteristics, patients randomized to
cinacalcet experienced a nominally significant 13% lower adjusted risk (95% confidence limit 4-20%) of the primary composite end point. The effect of
cinacalcet was not modified by baseline pulse pressure (Pinteraction=0.44). In adjusted models, at 20 weeks
cinacalcet resulted in a 2.2 mm Hg larger average decrease in systolic blood pressure (P=0.002) and a 1.3 mm Hg larger average decrease in diastolic blood pressure (P=0.002) compared with placebo. In summary, in the EVOLVE trial, the effect of
cinacalcet on death and major cardiovascular events was independent of baseline pulse pressure.