title: Aliskiren as add-on therapy in the treatment of hypertensive diabetic patients inadequately controlled with valsartan/HCT combination: a placebo-controlled study.
abstract: BACKGROUND
  Hypertension frequently coexists with diabetes mellitus, resulting in increased cardiovascular risk. Thus, BP control is crucial in decreasing morbidity and mortality in this difficult-to-treat patient population.
  
  
  OBJECTIVE
  The objective of this study was to evaluate the efficacy and safety of aliskiren in hypertensive patients with diabetes not adequately responsive to the combination of valsartan and hydrochlorothiazide (HCT).
  
  
  METHODS
  After a 1- to 4-week washout period, patients with a mean sitting diastolic BP (msDBP) ≥95 mmHg were treated with valsartan 160 mg for 2 weeks followed by valsartan/HCT 160 mg/25 mg for an additional 4 weeks (single-blind active run-in period). Patients whose msDBP remained ≥85 mmHg after the active run-in period were randomized (1 : 1) to receive aliskiren 150 mg (n = 184) or placebo (n = 179) as add-on therapy for 6 weeks. Aliskiren was then force-titrated to 300 mg once daily for another 6 weeks. Efficacy variables were: the change in msDBP and mean sitting systolic BP (msSBP) from baseline to week 12 endpoint, diastolic response (msDBP <80 mmHg or reduction of at least 10 mmHg), and BP control rate (<130/80 mmHg).
  
  
  RESULTS
  Of the 363 patients randomized, 328 (90.4%) completed the study (aliskiren and placebo groups: 89.7% and 91.1%, respectively). At week 12 endpoint, the least squares mean (LSM) changes in msDBP (aliskiren vs placebo: -5.8 vs -4.8 mmHg; p = 0.2767) and msSBP (aliskiren vs placebo: -7.3 vs -4.8 mmHg; p = 0.0725) were numerically greater in patients treated with aliskiren compared with those treated with placebo; however, this difference was not statistically significant. The proportion of diastolic responders (aliskiren and placebo: 68.5% and 72.9%, respectively; p = 0.8482) and patients achieving BP control (aliskiren and placebo: 16.0% and 16.4%, respectively; p = 0.7511) were similar for both groups. Overall, 63 (34%) and 59 (33%) patients in the aliskiren and placebo groups, respectively, experienced adverse events (AEs). The most commonly reported AEs were headache (placebo group: 6.1%) and dizziness (aliskiren group: 4.4%). Aliskiren was well tolerated.
  
  
  CONCLUSIONS
  The reductions in BP with aliskiren added to valsartan/HCT in this study were numerically greater compared with placebo added to valsartan/HCT, although not statistically significant.
authors.affiliation: Renaissance Clinical Research and Hypertension Center, Dallas, TX, USA. rcrh@swbell.net
authors.forename: W
authors.initials: W
authors.lastname: Drummond
authors.forename: Y M
authors.initials: YM
authors.lastname: Sirenko
authors.forename: E
authors.initials: E
authors.lastname: Ramos
authors.forename: I
authors.initials: I
authors.lastname: Baek
authors.forename: D L
authors.initials: DL
authors.lastname: Keefe
mesh_terms: D000368:Aged; D000577:Amides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017311:Amlodipine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004351:Drug Resistance; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D005650:Fumarates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010352:Patient Dropouts; D011188:Potassium / Q000097:blood; D016037:Single-Blind Method
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; D006852:Hydrochlorothiazide; D017311:Amlodipine; C446481:aliskiren; D011188:Potassium