title: Zofenopril plus hydrochlorothiazide and irbesartan plus hydrochlorothiazide in previously treated and uncontrolled diabetic and non-diabetic essential hypertensive patients.
abstract: BACKGROUND
  In most treated patients with hypertension, a two or more drug combination is required to achieve adequate blood pressure (BP) control. In our study we assessed whether the combination of zofenopril + hydrochlorothiazide (HCTZ) was at least as effective as irbesartan + HCTZ in essential hypertensives with at least one additional cardiovascular risk factor, uncontrolled by a previous monotherapy.
  
  
  METHODS
  After a 2-week placebo washout, 361 treated hypertensive patients [office sitting diastolic BP (DBP), ≥90 mmHg], aged 18-75 years, were randomized double blind to 18-week treatment with zofenopril 30 mg plus HCTZ 12.5 mg or irbesartan 150 mg plus HCTZ 12.5 mg once daily, in an international, multicenter study. After the first 6 and 12 weeks, zofenopril and irbesartan doses could be doubled in non-normalized subjects. The primary study end point was the office sitting DBP reduction after 18 weeks of treatment. Secondary end points included office systolic BP (SBP), ambulatory BP and high sensitivity C-reactive protein (hs-CRP).
  
  
  RESULTS
  The between-treatment difference for office DBP averaged to +1.0 (95% CI -0.4, +0.8) mmHg (P = 0.150), the upper limit of the 95% confidence interval being inferior to the protocol-defined non-inferiority limit (3 mmHg). In the subset of patients with valid ambulatory BP, no difference in 24-h average DBP [n = 181; 6.7 (8.7, 4.6) zofenopril + HCTZ vs. 6.3 (8.8, 3.7) mmHg irbesartan + HCTZ, P = 0.810] and SBP reductions [11.7 (15.4, 8.0) vs. 12.6 (17.2, 8.0) mmHg, P = 0.758] were observed between the two treatment groups. hs-CRP was reduced by zofenopril + HCTZ [-0.52 (-1.05, 0.01) mg/L], while it was increased by irbesartan plus HCTZ [0.97 (0.29, 1.65) mg/L, P = 0.001 between treatments].
  
  
  CONCLUSIONS
  In previously monotherapy-treated, uncontrolled patients with hypertension, zofenopril 30-60 mg + HCTZ 12.5 mg is as effective as irbesartan 150-300 mg plus HCTZ 12.5 mg, with the added value of a potential protective effect against vascular inflammation.
authors.affiliation: Division of Medicine and Surgery, Spedali Civili and University of Brescia, Brescia, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Agabiti-Rosei
authors.forename: Athanasios
authors.initials: A
authors.lastname: Manolis
authors.forename: Dario
authors.initials: D
authors.lastname: Zava
authors.forename: Stefano
authors.initials: S
authors.lastname: Omboni
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D002216:Captopril / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016022:Case-Control Studies; D048909:Diabetes Complications; D003920:Diabetes Mellitus; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy*; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D013777:Tetrazoles; D006852:Hydrochlorothiazide; C044958:zofenopril; D002216:Captopril; D000077405:Irbesartan