The effects of cinacalcet on blood pressure, mortality and cardiovascular endpoints in the EVOLVE trial
T I Chang1, S Abdalla1, G M London2
1Department of Medicine, Stanford University School of Medicine, Palo Alto, CA, USA.
Insights
Cinacalcet, used for secondary hyperparathyroidism in dialysis patients, did not show a significant reduction in cardiovascular events in the EVOLVE trial. However, it did lower blood pressure, independent of arterial stiffness markers.
Area of Science:
- Nephrology
- Cardiology
- Clinical Trials
Background:
- End-stage renal disease (ESRD) patients often have mineral metabolism disorders, leading to secondary hyperparathyroidism (sHPT).
- sHPT is linked to arterial stiffness and hypertension, increasing cardiovascular risk in ESRD patients.
- The Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) trial investigated cinacalcet's efficacy in this population.
Purpose of the Study:
- To assess if cinacalcet's effect on cardiovascular events and mortality is modified by baseline pulse pressure, a marker of arterial stiffness.
- To determine cinacalcet's impact on blood pressure in patients with ESRD and sHPT.
Main Methods:
- Secondary analysis of the randomized, placebo-controlled EVOLVE trial.
- Patients on hemodialysis with sHPT were assigned to cinacalcet or placebo.
- Statistical adjustments were made for baseline characteristics to evaluate treatment effects and interactions.
Main Results:
- An unadjusted analysis did not find cinacalcet reduced the primary composite endpoint (death or major cardiovascular events).
- After adjustment, cinacalcet showed a nominally significant 13% lower adjusted risk of the primary endpoint.
- Cinacalcet significantly reduced systolic blood pressure by 2.2 mmHg and diastolic blood pressure by 1.3 mmHg at 20 weeks compared to placebo.
- The treatment effect on the primary endpoint was not modified by baseline pulse pressure (Pinteraction=0.44).
Conclusions:
- In the EVOLVE trial, cinacalcet's effect on major cardiovascular events and mortality was independent of baseline arterial stiffness.
- Cinacalcet effectively lowered blood pressure in patients with ESRD and sHPT.
- These findings suggest cinacalcet may offer cardiovascular benefits through blood pressure reduction in ESRD patients, irrespective of arterial stiffness.
Abstract:
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.
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