title: Efficacy and safety of LCI699 for hypertension: a meta-analysis of randomized controlled trials and systematic review.
abstract: OBJECTIVE
  This study reviews the available data from randomized controlled trials on efficacy and safety of LCI699, a novel inhibitor of aldosterone synthase, as treatment of hypertension.
  
  
  METHODS
  We performed a meta-analysis of phase II randomized, controlled trials comparing the efficacy/safety of LCI699 with placebo in hypertension patients. For this purpose, PubMed, Embase, Cochrane Library database, ISI-Science Citation Index, and the Chinese Biomedicine Literature Database were searched until August 2013. The available data on mean sitting systolic blood pressure (MSSBP), mean sitting diastolic blood pressure (MSDBP), adverse effects, renin-angiotensin-aldosterone system biomarkers (RAASB) and adrenocorticotropic hormone-stimulated cortisol concentration (AHSC) were collected. All data were analyzed using Review Manager, version 5.2.
  
  
  RESULTS
  The present study finally included three randomized controlled trials, comprising of 623 patients in total. The daily use of ≥ 1 mg LCI699 was associated with a significant reduction of MSSBP (Weighted mean difference/WMD = -8.80, 95% CI: -11.31 to -5.68, p < 0.00001, I2 = 0%) and MSDBP (WMD = -4.94, 95% CI: -7.49 to -2.40, p = 0.00001, I2 = 9%). Adverse reactions occurred in 73 of the 139 patients (52.51%) treated with LCI699 and in 34 of the 63 patients (53.96%) treated with placebo. Pooled meta-analysis showed that the use of LCI699 was associated with no increased risk of side effects compared with placebo (RR = 0.90; 95% CI: 0.68 to 1.18, p = 0.43, I2 = 0%). Suppression of plasma aldosterone was measured at all doses of LCI699 treatment groups. LCI699 suppressed the ACTH-stimulated cortisol response in a dose- and time-dependent manner.
  
  
  CONCLUSIONS
  Current evidence indicates that the novel aldosterone inhibitor LCI699 is an effective and well-tolerated antihypertensive agent that lowers plasma aldosterone concentration and produces a mild ACTH-stimulated cortisol response suppressive effect.
authors: Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA. hwang20@tulane.edu.
authors: H-Z
authors: HZ
authors: Wang
authors: J-B
authors: JB
authors: Tian
authors: K H
authors: KH
authors: Yang
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use; D017322:Clinical Trials, Phase II as Topic; D019405:Cytochrome P-450 CYP11B2 / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D015337:Multicenter Studies as Topic; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
chemical_list: D000959:Antihypertensive Agents; D007093:Imidazoles; D011725:Pyridines; C553306:Osilodrostat; D019405:Cytochrome P-450 CYP11B2