title: Comparison of the blood pressure-lowering effects and tolerability of Losartan- and Amlodipine-based regimens in patients with isolated systolic hypertension.
abstract: BACKGROUND
  Elevated systolic blood pressure is a more important risk factor for cardiovascular and renal disease than elevated diastolic blood pressure. Isolated systolic hypertension (ISH) is the predominant form of hypertension in the elderly. Effects of angiotensin II on the vascular wall and endothelium may contribute to development of ISH.
  
  
  OBJECTIVE
  The primary objective of this study was to compare the effects on trough sitting systolic blood pressure (SiSBP) of a regimen of losartan, a selective angiotensin II-receptor antagonist, and an amlodipine-based regimen in patients with ISH.
  
  
  METHODS
  This multicenter, prospective, randomized, double-blind, parallel-group study consisted of a 4-week placebo phase and an 18-week active-treatment phase. The losartan-based regimen consisted of losartan 50 mg, increased as needed to losartan 50 mg/hydrochlorothiazide (HCTZ) 12.5 mg at week 6 and to losartan 100 mg/HCTZ 25 mg at week 12 to achieve a target SiSBP <140 mm Hg. the amlodipine-based regimen consisted of amlodipine 5 mg, increased as needed to amlodipine 10 mg at week 6 and to amlodipine 10 mg/HCTZ 25 mg at week 12. The primary efficacy measure was change in trough SiSBP from baseline to week 18. Information on the tolerability of study treatments was collected at each visit, including the investigator's and patient's observations of clinical adverse experiences (CAEs), laboratory adverse experiences, and responses to a symptom questionnaire.
  
  
  RESULTS
  Eight hundred fifty-seven patients (65.6% female) were randomized to treatment, 432 in the losartan group and 425 in the amlodipine group. Their mean age was 67.6 years, and they had a mean duration of hypertension of 6.7 years at baseline. The losartan and amlodipine groups (intent-to-treat population) had baseline mean SiSBP values of 171.2 and 171.9 mm Hg, respectively. At week 18 (the primary end point), the mean change from baseline in SiSBP was -27.4 mm Hg for 426 patients who received losartan and -28.1 mm Hg for 419 patients who received amlodipine (estimated least-square mean difference, 0.3 mm Hg; 95% CI, -1.4 to 2.0), indicating that losartan's effect on systolic blood pressure was noninferior to that of amlodipine. The proportion of patients who responded (SiSBP <140 mm Hg or a > or =20-mm Hg decrease in SiSBP from baseline) was comparable between groups (73.9% losartan, 75.4% amlodipine). The incidence of CAEs and drug-related CAEs was significantly greater in the amlodipine group (amlodipine, 79.8% and 43.8%, respectively; losartan, 67.8% and 25.5%; P < or = 0.001). In addition, more patients in the amlodipine group discontinued therapy due to a drug-related CAE compared with patients in the losartan group (12.9% vs 4.4%, respectively; P < or = 0.001). Lower-extremity edema was the most common drug-related CAE in the amlodipine group (24.0% amlodipine, 2.5% losartan; P < or = 0.001); dizziness was the most common drug-related CAE in the losartan group (6.0% losartan, 4.0% amlodipine).
  
  
  CONCLUSIONS
  In these patients with ISH, losartan and amlodipine produced comparable clinically relevant reductions in SiSBP; however, losartan was better tolerated, as evidenced by fewer CAEs and discontinuations compared with amlodipine. Losartan may be considered for the initial treatment of ISH.
authors.affiliation: Universitá degli Studi di Roma "La Sapienza", Rome, Italy. volpe@uniromal.it
authors.forename: Massimo
authors.initials: M
authors.lastname: Volpe
authors.forename: Zhu
authors.initials: Z
authors.lastname: Junren
authors.forename: Thomas
authors.initials: T
authors.lastname: Maxwell
authors.forename: Aldo
authors.initials: A
authors.lastname: Rodriguez
authors.forename: Raul
authors.initials: R
authors.lastname: Gamboa
authors.forename: Pablo
authors.initials: P
authors.lastname: Gomez-Fernandez
authors.forename: Ginés
authors.initials: G
authors.lastname: Ortega-Gonzalez
authors.forename: Norberta
authors.initials: N
authors.lastname: Matadamas
authors.forename: Freddy
authors.initials: F
authors.lastname: Rodriguez
authors.forename: Badal
authors.initials: B
authors.lastname: Dass
authors.forename: Chris
authors.initials: C
authors.lastname: Kyle
authors.forename: Laurent
authors.initials: L
authors.lastname: Clarysse
authors.forename: Alfonso
authors.initials: A
authors.lastname: Bryce
authors.forename: Ernesto
authors.initials: E
authors.lastname: Moreno-Heredia
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Germano
authors.forename: Leen
authors.initials: L
authors.lastname: Gilles
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Smith
authors.forename: John E
authors.initials: JE
authors.lastname: Sanderson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; 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; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D019808:Losartan / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged
chemical_list: D000959:Antihypertensive Agents; D017311:Amlodipine; D019808:Losartan