Long-term safety and efficacy of aliskiren and valsartan combination with or without the addition of HCT in patients with hypertension.
OBJECTIVE
To assess the long-term safety and antihypertensive efficacy of aliskiren/valsartan 300/320 mg combination.


METHODS
This was a 54-week, multicenter, open-label study (core phase), followed by a 26-week extension phase. Efficacy variables were change in msDBP and msSBP from baseline to endpoint (54-week and 80-week). Safety was assessed by monitoring and recording adverse events (AEs). ClinicalTrials.gov Identifier: NCT00386607 RESULTS: A total of 601 patients (msDBP ≥ 90 and <110 mmHg) entered the 54-week core study. Optional add-on HCT was allowed at week 10 onwards if BP was ≥ 140/90 mmHg at two consecutive visits. Of the 486 patients completed the core study, 180 patients entered the extension phase and received aliskiren/valsartan and add-on HCT (12.5 or 25 mg). Overall the combination of aliskiren/valsartan was well-tolerated and the majority of AEs were mild-to-moderate in severity. The incidence of SAEs was low (core phase: n = 22 [3.7%]; extension phase: n = 4 [2.2%]). Elevated serum potassium (>5.5 mmol/L at any time during the study) was observed in 21 (3.6%) patients. The majority of these elevations were transient and returned to normal in subsequent visits, and the discontinuation rate due to elevated serum potassium was low (0.3% [n = 2]). Decreased serum potassium levels (<3.5 mmol/L at any time during the study) was observed in 26 (4.4%) patients, mainly in patients receiving aliskiren/valsartan/HCT (n = 22; 7.1%). At the 54-week endpoint, a mean BP reduction of 20.5/13.4 mmHg from baseline (baseline BP: 152.9/97.0 mmHg) was observed and 66.9% (n = 398/595) of patients achieved BP control with aliskiren/valsartan with or without HCT. At the end of the extension phase (80-week endpoint), additional reduction in BP was obtained (overall, 28.8/18.3 mmHg) and 86.6% (n = 155/179) of patients achieved BP control with aliskiren/valsartan/HCT. A limitation is the absence of an active comparator group.


CONCLUSIONS
Long-term treatment with the combination of aliskiren/valsartan with or without HCT provided clinically meaningful BP reductions and high rates of BP control and was well-tolerated.
University of Oklahoma, Oklahoma City, OK, USA. schrysant@yahoo.com
Steven G
SG
Chrysant
Alexander V
AV
Murray
Uta C
UC
Hoppe
Dan
D
Dattani
Samir
S
Patel
Shannon
S
Ritter
Jack
J
Zhang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000577:Amides / Q000008:administration & dosage* / Q000009:adverse effects; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects; D004338:Drug Combinations; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D005650:Fumarates / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage* / Q000009:adverse effects; D006973:Hypertension / Q000188:drug therapy* / Q000453:epidemiology; D015994:Incidence; D008297:Male; D008875:Middle Aged; D013777:Tetrazoles / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D014633:Valine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000068756:Valsartan; D055815:Young Adult
D000577:Amides; D000959:Antihypertensive Agents; D004338:Drug Combinations; D005650:Fumarates; D013777:Tetrazoles; D006852:Hydrochlorothiazide; C446481:aliskiren; D000068756:Valsartan; D014633:Valine