title: Combined olmesartan, amlodipine, and hydrochlorothiazide therapy in randomized patients with hypertension: a subgroup analysis of the TRINITY study by age.
abstract: BACKGROUND
  Hypertension is often inadequately controlled in older people.
  
  
  OBJECTIVE
  This prespecified subgroup analysis assessed the efficacy and safety of an olmesartan medoxomil (OM) 40 mg/amlodipine besylate (AML) 10 mg/hydrochlorothiazide (HCTZ) 25 mg triple-combination treatment compared with the 3 components as dual-combination treatments in participants with hypertension who were <65 and ≥ 65 years of age. Within the ≥ 65 years of age subgroup, efficacy and safety were also summarized for participants ≥ 75 years of age.
  
  
  METHODS
  12-week, multicenter, double-blind, randomized, parallel-group study.
  
  
  METHODS
  317 ambulatory care sites in the US and Puerto Rico.
  
  
  METHODS
  Individuals ≥ 18 years of age with mean seated blood pressure (SeBP) ≥ 140/100 or ≥ 160/90 mmHg off antihypertensive medication on 2 consecutive clinic visits with no recent history of significant cerebrovascular disease, coronary artery disease, heart failure (New York Heart Association class III or IV), severe renal insufficiency, or uncontrolled diabetes (HbA1c >9 %).
  
  
  METHODS
  Participants were randomized, stratified by age, diabetes status, and race to one of four treatment assignments: OM 40/AML 10/HCTZ 25 mg, OM 40/AML 10 mg, OM 40/HCTZ 25 mg, or AML 10/HCTZ 25 mg.
  
  
  METHODS
  Least squares (LS) mean change from baseline in seated diastolic blood pressure (SeDBP) at week 12 (last observation carried forward) in each age subgroup (prespecified analysis).
  
  
  RESULTS
  Of the 2492 randomized participants in the study (total cohort), 2021 (81.1 %) were <65 and 471 (18.9 %) were ≥ 65 years of age, including 79 (3.2 %) who were ≥ 75 years of age. OM 40/AML 10/HCTZ 25 mg triple-combination treatment resulted in a significantly greater reduction in LS mean SeDBP at week 12 than dual-combination component treatments in participants in both cohorts: <65 years (21.0 vs. 14.2-17.2 mmHg; p < 0.0001) and ≥ 65 years (23.7 vs. 17.3-20.0 mmHg; p ≤ 0.002). Similarly, triple-combination treatment resulted in a greater reduction in LS mean seated systolic blood pressure (SeSBP) at week 12 than dual-combination component treatments: <65 years (38.2 vs. 28.3-31.4 mmHg; p < 0.0001) and ≥ 65 years (39.2 vs. 29.3-31.1 mmHg; p < 0.0001). Triple-combination treatment was more effective than dual-combination treatments in enabling participants to reach SeBP goal (<140/90 mmHg [<130/80 mmHg in participants with diabetes, chronic kidney disease, or chronic cardiovascular disease]) in both age subgroups (<65 years: 65 vs. 34-50 %, respectively, p < 0.0001 and ≥ 65 years: 63 vs. 32-39 %; p ≤ 0.0004). All 4 treatments were safe and well tolerated with low discontinuation rates in both age subgroups. There were no clinically relevant differences in the incidence of treatment-emergent adverse events between participants <65 and ≥ 65 years of age receiving triple-combination treatment.
  
  
  CONCLUSIONS
  Triple-combination treatment with OM 40/AML 10/HCTZ 25 mg was well tolerated and more effective in lowering BP than the component dual-combination treatments in elderly and non-elderly subgroups.
authors.affiliation: National Research Institute, 2010 Wilshire Blvd. Ste. 302, Los Angeles, CA 90057, USA. docl@clinical-studies.com
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lewin
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Izzo
authors.forename: Michael
authors.initials: M
authors.lastname: Melino
authors.forename: James
authors.initials: J
authors.lastname: Lee
authors.forename: Victor
authors.initials: V
authors.lastname: Fernandez
authors.forename: Reinilde
authors.initials: R
authors.lastname: Heyrman
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D017311:Amlodipine / Q000009:adverse effects / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000009:adverse effects / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy*; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000068557:Olmesartan Medoxomil; D013777:Tetrazoles / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000959:Antihypertensive Agents; D004338:Drug Combinations; D007093:Imidazoles; D013777:Tetrazoles; D006852:Hydrochlorothiazide; D017311:Amlodipine; D000068557:Olmesartan Medoxomil
references.citation: J Am Coll Cardiol. 2011 May 17;57(20):2037-114
references.pmid: 21524875
references.citation: Clin Ther. 2007 May;29(5):972-984
references.pmid: 17697916
references.citation: Lancet. 1997 Sep 13;350(9080):757-64
references.pmid: 9297994
references.citation: BMJ. 1992 Feb 15;304(6824):405-12
references.pmid: 1445513
references.citation: Popul Health Metr. 2010 Oct 22;8:29
references.pmid: 20969750
references.citation: Lancet. 1985 Jun 15;1(8442):1349-54
references.pmid: 2861311
references.citation: J Hum Hypertens. 2011 Jun;25(6):354-63
references.pmid: 20686499
references.citation: Clin Drug Investig. 2012 Oct 1;32(10):649-64
references.pmid: 22909147
references.citation: Curr Med Res Opin. 2008 Sep;24(9):2597-607
references.pmid: 18812017
references.citation: Circulation. 2013 Jan 1;127(1):143-52
references.pmid: 23283859
references.citation: Circulation. 2008 Jul 1;118(1):42-8
references.pmid: 18559700
references.citation: Cochrane Database Syst Rev. 2009 Oct 07;(4):CD000028
references.pmid: 19821263
references.citation: NCHS Data Brief. 2010 Oct;(48):1-8
references.pmid: 21050532
references.citation: J Clin Hypertens (Greenwich). 2002 Nov-Dec;4(6):393-404
references.pmid: 12461301
references.citation: Drugs Aging. 2011 Jun 1;28(6):477-90
references.pmid: 21639407
references.citation: Clin Ther. 2010 Jul;32(7):1252-69
references.pmid: 20678674
references.citation: J Am Soc Hypertens. 2010 Jan-Feb;4(1):42-50
references.pmid: 20374950
references.citation: Cardiovasc Diabetol. 2012 Oct 30;11:134
references.pmid: 23110471
references.citation: J Hypertens. 2012 Jul;30(7):1468-77
references.pmid: 22573127
references.citation: J Clin Hypertens (Greenwich). 2010 Nov;12(11):869-78
references.pmid: 21054774
references.citation: Lancet. 2005 Jan 15-21;365(9455):217-23
references.pmid: 15652604
references.citation: Curr Med Res Opin. 2010 Dec;26(12):2877-87
references.pmid: 21067459
references.citation: Curr Med Res Opin. 2010 Sep;26(9):2065-76
references.pmid: 20629600
references.citation: J Hypertens. 1998 Dec;16(12 Pt 1):1823-9
references.pmid: 9869017
references.citation: J Clin Hypertens (Greenwich). 2010 Jan;12(1):3-13
references.pmid: 20047622
references.citation: JAMA. 1991 Jun 26;265(24):3255-64
references.pmid: 2046107
references.citation: JAMA. 2003 Apr 23-30;289(16):2073-82
references.pmid: 12709465
references.citation: Hypertension. 2009 Jul;54(1):19-22
references.pmid: 19470871
references.citation: Vasc Health Risk Manag. 2007;3(6):999-1005
references.pmid: 18200818
references.citation: J Clin Hypertens (Greenwich). 2009 Aug;11(8):411-21
references.pmid: 19695028
references.citation: Clin Ther. 2008 Aug;30(8):1558-63
references.pmid: 18803997
references.citation: Hypertension. 2010 Feb;55(2):399-407
references.pmid: 20026768
references.citation: Eur J Cardiovasc Prev Rehabil. 2005 Jun;12(3):243-9
references.pmid: 15942423
references.citation: Arch Intern Med. 2005 May 23;165(10):1147-52
references.pmid: 15911728
references.citation: Lancet. 2005 Sep 10-16;366(9489):895-906
references.pmid: 16154016
references.citation: Lancet. 1991 Nov 23;338(8778):1281-5
references.pmid: 1682683
references.citation: Hypertension. 2003 Dec;42(6):1206-52
references.pmid: 14656957
references.citation: Lancet. 2002 Dec 14;360(9349):1903-13
references.pmid: 12493255
references.citation: Arch Intern Med. 2008 Feb 11;168(3):271-6
references.pmid: 18268167
references.citation: J Hypertens. 2010 Nov;28(11):2342-50
references.pmid: 20829713
references.citation: Arzneimittelforschung. 2011;61(4):221-8
references.pmid: 21650080
references.citation: Am J Med. 2007 Aug;120(8):713-9
references.pmid: 17679131
references.citation: N Engl J Med. 2008 May 1;358(18):1887-98
references.pmid: 18378519
references.citation: J Hum Hypertens. 2010 Dec;24(12):831-8
references.pmid: 20200547
references.citation: Expert Opin Pharmacother. 2009 Aug;10(12):1869-74
references.pmid: 19496740
references.citation: Am J Med. 1991 Mar;90(3A):60S-61S
references.pmid: 2006663
references.citation: J Hypertens. 2003 May;21(5):875-86
references.pmid: 12714861
references.citation: N Engl J Med. 2008 Dec 4;359(23):2417-28
references.pmid: 19052124
references.citation: P T. 2008 Nov;33(11):652-66
references.pmid: 19750061