PMID- 22035463
OWN - NLM
STAT- MEDLINE
DCOM- 20120905
LR  - 20211020
IS  - 1179-1918 (Electronic)
IS  - 1173-2563 (Linking)
VI  - 31
IP  - 12
DP  - 2011 Dec 1
TI  - Long-term safety and tolerability of the oral direct renin inhibitor aliskiren 
      with optional add-on hydrochlorothiazide in patients with hypertension: a 
      randomized, open-label, parallel-group, multicentre, dose-escalation study with 
      an extension phase.
PG  - 825-37
AB  - BACKGROUND: Most patients with hypertension will require combination therapy with 
      at least two agents from different antihypertensive classes to achieve blood 
      pressure (BP) control. Thiazide diuretics, such as hydrochlorothiazide (HCTZ), 
      are widely used in combination therapy. The volume reduction with these agents 
      stimulates the renin-angiotensin system (RAS), making RAS inhibitors such as the 
      direct renin inhibitor aliskiren a logical choice for combination therapy with 
      HCTZ. OBJECTIVE: The aim of this study was to investigate the long-term safety, 
      tolerability and efficacy of the direct renin inhibitor aliskiren, with or 
      without addition of the diuretic HCTZ. METHODS: In the 12-month core study, 
      patients with hypertension (mean sitting diastolic BP >/=90 mmHg and <110 mmHg) 
      were randomized in a 3 : 2 ratio to once-daily aliskiren 150 mg or 300 mg. At 
      months 2, 3, 4, 6 and 9, treatment was adjusted in patients not achieving a BP 
      goal of <140/90 mmHg. Patients not at goal on aliskiren 150 mg once daily were 
      up-titrated to aliskiren 300 mg once daily. Patients not at goal with aliskiren 
      300 mg once daily received add-on HCTZ 12.5 mg once daily, which was up-titrated 
      to 25 mg once daily if BP remained inadequately controlled. At month 12, patients 
      who received aliskiren/HCTZ 300 mg/25 mg once daily for at least 8 months in the 
      core study were eligible to enter a 4-month extension study. RESULTS: Overall, 
      1625/1955 patients completed the core study, and 870/1955 patients received 
      add-on HCTZ; 189/198 patients completed the 4-month extension. Aliskiren, with or 
      without add-on HCTZ, was generally well tolerated; the incidence of adverse 
      events (AEs) during the core study was similar among the four final treatment 
      groups. The most frequently reported AEs in the core and extension studies were 
      mild and transient cases of nasopharyngitis, headache and dizziness. Few patients 
      exhibited laboratory abnormalities. Overall, aliskiren, with or without add-on 
      HCTZ, reduced mean BP by 18.0/12.7 mmHg at core study endpoint, and 61.2% of 
      patients achieved BP control. BP reductions with aliskiren/HCTZ 300 mg/25 mg 
      combination therapy at the core study endpoint were maintained during the 
      extension study. CONCLUSION: In patients with hypertension, long-term treatment 
      with aliskiren, with or without add-on HCTZ, is well tolerated and provides 
      effective BP lowering that is sustained over 12 months.
FAU - Sica, Domenic
AU  - Sica D
AD  - Virginia Commonwealth University Health System, Richmond, USA.
FAU - Gradman, Alan H
AU  - Gradman AH
FAU - Lederballe, Ole
AU  - Lederballe O
FAU - Kolloch, Rainer E
AU  - Kolloch RE
FAU - Zhang, Jack
AU  - Zhang J
FAU - Keefe, Deborah L
AU  - Keefe DL
LA  - eng
SI  - ClinicalTrials.gov/NCT00219037
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - New Zealand
TA  - Clin Drug Investig
JT  - Clinical drug investigation
JID - 9504817
RN  - 0 (Amides)
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Diuretics)
RN  - 0 (Fumarates)
RN  - 0J48LPH2TH (Hydrochlorothiazide)
RN  - 502FWN4Q32 (aliskiren)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Amides/adverse effects/*pharmacology/therapeutic use
MH  - Antihypertensive Agents/adverse effects/*pharmacology/therapeutic use
MH  - Blood Pressure/*drug effects
MH  - Diuretics/adverse effects/*pharmacology/therapeutic use
MH  - Dose-Response Relationship, Drug
MH  - Drug Therapy, Combination
MH  - Female
MH  - Follow-Up Studies
MH  - Fumarates/adverse effects/*pharmacology/therapeutic use
MH  - Humans
MH  - Hydrochlorothiazide/adverse effects/*pharmacology/therapeutic use
MH  - Hypertension/drug therapy/physiopathology
MH  - Male
MH  - Middle Aged
MH  - Renin-Angiotensin System/*drug effects
MH  - Time Factors
MH  - Young Adult
EDAT- 2011/11/01 06:00
MHDA- 2012/09/06 06:00
CRDT- 2011/11/01 06:00
PHST- 2011/11/01 06:00 [entrez]
PHST- 2011/11/01 06:00 [pubmed]
PHST- 2012/09/06 06:00 [medline]
AID - 3 [pii]
AID - 10.1007/BF03256921 [doi]
PST - ppublish
SO  - Clin Drug Investig. 2011 Dec 1;31(12):825-37. doi: 10.1007/BF03256921.