title: Efficacy and Safety Study of Olmesartan Medoxomil, Amlodipine, and Hydrochlorothiazide Combination Therapy in Patients with Hypertension Not Controlled with Olmesartan Medoxomil and Hydrochlorothiazide Combination Therapy: Results of a Randomized, Double-Blind, Multicenter Trial.
abstract: BACKGROUND
  This study was to evaluate the efficacy and safety of triple fixed-dose combination (FDC) therapy with olmesartan medoxomil (OM) 20 mg, amlodipine (AML) 5 mg, and hydrochlorothiazide (HCTZ) 12.5 mg (OM/AML/HCTZ 20/5/12.5) in Korean patients with moderate hypertension not controlled with dual FDC therapy (OM/HCTZ 20/12.5).
  
  
  METHODS
  In this multicenter, randomized, double-blind, parallel-group study, Korean patients aged 20 to 75 years with stage 2 hypertension who had a mean seated diastolic blood pressure (msDBP) ≥100 mmHg were enrolled when their BP was uncontrolled [mean seated systolic BP (msSBP)/msDBP >140/90 mmHg or msSBP/msDBP >130/80 mmHg with diabetes or chronic kidney disease] with 4-week dual FDC therapy (OM/HCTZ 20/12.5). The patients were randomized to receive either OM/AML/HCTZ 20/5/12.5 or OM/HCTZ 20/12.5 once daily for 8 weeks. At the end of 8 weeks, patients with uncontrolled BP were assigned to receive either OM/AML/HCTZ 40/5/12.5 or OM/AML/HCTZ 20/5/12.5 in an additional 8-week open-label extension period.
  
  
  RESULTS
  A total of 623 patients received a 4-week run-in treatment with OM/HCTZ, 341 patients were randomized, and finally, 167 patients in the OM/AML/HCTZ group and 171 patients in the OM/HCTZ group were analyzed for the full analysis set. Non-responders after the 8 weeks of double-blind treatment continued the 8-week open-label treatment with OM/AML/HCTZ 40/5/12.5 mg (n = 32) or OM/AML/HCTZ 20/5/12.5 mg (n = 71). After 8 weeks of double-blind treatment, the changes in msDBP were -9.50 (8.46) mmHg in the OM/AML/HCTZ group and -4.23 (7.41) mmHg in the OM/HCTZ group (both p < 0.0001 vs. baseline; p < 0.0001 between groups). The response rates for both msSBP and msDBP at week 8 were 65.27 % in the OM/AML/HCTZ group and 37.43 % in the OM/HCTZ group (p < 0.0001 between groups). The response rates for both msSBP and msDBP at week 16 after open-label treatment were 18.75 % in the OM/AML/HCTZ 40/5/12.5 group and 46.48 % in the OM/AML/HCTZ 20/5/12.5 group (p = 0.0073 between groups). All medications were well tolerated.
  
  
  CONCLUSIONS
  In Korean patients with moderate hypertension not controlled with dual FDC therapy (OM/HCTZ 20/12.5) as first-line therapy, switching to triple FDC therapy (OM/AML/HCTZ 20/5/12.5) was associated with significant BP reductions and greater achievement of BP goals, and was well tolerated (ClinicalTrials.gov Identifier: NCT01838850).
authors.affiliation: Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea.
authors.forename: Il Suk
authors.initials: IS
authors.lastname: Sohn
authors.affiliation: Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea.
authors.forename: Chong-Jin
authors.initials: CJ
authors.lastname: Kim
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, 101 Daehak-ro(28 Yongon-dong), Jongno-gu, Seoul, 110-744, Republic of Korea. ohbhmed@snu.ac.kr.
authors.forename: Byung-Hee
authors.initials: BH
authors.lastname: Oh
authors.affiliation: Pusan National University Hospital, Busan, Republic of Korea.
authors.forename: Taek-Jong
authors.initials: TJ
authors.lastname: Hong
authors.affiliation: Korea University Guro Hospital, Seoul, Republic of Korea.
authors.forename: Chang-Gyu
authors.initials: CG
authors.lastname: Park
authors.affiliation: Daedong Hospital, Busan, Republic of Korea.
authors.forename: Byung-Soo
authors.initials: BS
authors.lastname: Kim
authors.affiliation: Yeouido St. Mary's Hospital of the Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Woo-Baek
authors.initials: WB
authors.lastname: Chung
mesh_terms: D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000008:administration & dosage / Q000009:adverse effects; D000959:Antihypertensive Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000009:adverse effects* / Q000379:methods; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000009:adverse effects; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D000068557:Olmesartan Medoxomil / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D006852:Hydrochlorothiazide; D017311:Amlodipine; D000068557:Olmesartan Medoxomil