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.
Bibliographical noteFunding Information:
This study was funded by Amgen, Inc. and led by an Executive Committee composed of academic members, two Sponsor members (nonvoting), and statisticians. The Executive Committee oversaw the design, conduct, and all analyses. Data were collected by the Sponsor and shared with the Executive Committee throughout the study and after unblinding. The analysis was performed by an independent biostatistician (SA) at Stanford University School of Medicine. The Sponsor provided the active medication and matching placebo. The lead author wrote the first draft of the manuscript, and the Executive Committee was responsible for data interpretation and manuscript completion. The Sponsor reviewed the manuscript, but decisions about the final manuscript were made by the lead author and academic members of the Executive Committee only. All authors vouch for the integrity of the data. The lead author (TC), Executive Committee Co-Chair (GC), with the statistician (SA) independently performed all prespecified and exploratory analyses; these analyses were confirmed by Amgen statisticians. The results of the independent analyses are those reported in the manuscript.
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