期刊
CIRCULATION
卷 124, 期 18, 页码 1945-U124出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCULATIONAHA.111.029892
关键词
blood pressure; hypertension; inhibitors; trials
资金
- Novartis
- Novartis Pharma AG (Switzerland)
- Roche
- Actelion
Background-LCI699, a novel inhibitor of aldosterone synthase, reduces serum aldosterone, and may have benefit in the treatment of hypertension. Methods and Results-We performed the first double-blind, randomized trial with LCI699 in patients with primary hypertension. We randomized 524 patients to LCI699 0.25 mg once daily (n = 92), 0.5 mg once daily (n = 88), 1.0 mg once daily (n = 86), and 0.5 mg twice daily (n = 97); eplerenone 50 mg twice daily (n = 84); or placebo (n = 77) for 8 weeks. Adrenocorticotropic hormone (250 mu g IV) stimulation testing was performed in a subset of patients to quantify the selectivity of LCI699 for aldosterone synthase compared with 11-beta-hydroxylase. Reductions in clinic diastolic blood pressure were significant for LCI699 1.0 mg (-7.1 mm Hg; P = 0.0012) and eplerenone 50 mg twice daily (-7.9 mm Hg; P < 0.0001) compared with placebo (-2.6 mm Hg) but not other doses of LCI699. Significant reductions in clinic systolic blood pressure were observed with all doses of LCI699 (P < 0.005 or better) and eplerenone (P < 0.0001). All doses of LCI699 significantly reduced 24-hour ambulatory blood pressure compared with placebo (P < 0.01). Adrenocorticotropic hormone stimulation of cortisol was suppressed in approximate to 20% of subjects receiving LCI699 at a total daily dose of 1.0 mg. Safety and tolerability were similar among LCI699, placebo, and eplerenone. Conclusions-Aldosterone synthase inhibition with LCI699 significantly lowered clinic and ambulatory blood pressure. A minority of subjects developed blunted adrenocorticotropic hormone-stimulated release of cortisol. These results support additional research to evaluate use of aldosterone synthase inhibition in primary hypertension and/or patients characterized by aldosterone excess.
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