Effect of valsartan or olmesartan addition to amlodipine on ankle edema in hypertensive patients.
BACKGROUND
The objective of this study was to compare the effect on ankle edema of adding valsartan (V) or olmesartan (O) to amlodipine (A) in the treatment of hypertension.


METHODS
After a 4-week placebo period, 74 adult outpatients with essential hypertension (diastolic blood pressure [DBP] >90 and <110 mmHg, and systolic blood pressure [SBP] >140 mmHg) were treated with A 10 mg once daily for 4 weeks. Thereafter, nonresponder patients (DBP >90 mmHg and/or SBP >140 mmHg; n=51) were randomized to receive additional V 160 mg once daily or O 20 mg once daily for 8 weeks in two crossover periods, each separated by a 4-week placebo period. Clinic blood pressure (BP), heart rate, and ankle/foot volume (AFV) were evaluated and blood samples were drawn to evaluate plasma norepinephrine (NE) levels.


RESULTS
Both V/A and O/A induced a greater SBP/DBP reduction than A monotherapy (-26.4/-20.8 mmHg and -24.4/-19.1 mmHg, respectively; all P<0.001 vs. baseline and P<0.01 vs. A). A monotherapy increased AFV by 24%, P<0.001 vs. baseline, while the addition of either V or A reduced such increases. However, with V/A the AFV increase (+9.7%, P<0.05 vs. baseline, P<0.01 vs. A) was lower than with O/A (+16.7%, P<0.01 vs. baseline, P<0.05 vs. A); the difference between the two combinations was significant. Plasma NE levels were significantly increased by A (+44.6%) and values did not change with the addition of V (+35.2%) or O (+33.7%). Plasma active renin (PAR) was unchanged by A but increased by V/A (+214.4%, P<0.05 vs. baseline) and further by O/A (+325.6%, P<0.01 vs. baseline; difference between the 2 combinations: P<0.05). An inverse correlation was found between the AFV decrease and PAR increase (r=-0.31, P<0.05).


CONCLUSIONS
Adding V or O to A reduced ankle edema, but this effect was more pronounced with V. The greater degree of renin-angiotensin system activation observed with Ocould be related to such a difference.
Fogari
Roberto
R
Clinica Medica II, Centro Ipertensione e Fisiopatologia Cardiovascolare, Department of Internal Medicine and Therapeutics, University of Pavia, Italy. r.fogari@unipv.it
Malamani
Gian
G
Corradi
Luca
L
Mugellini
Amedeo
A
Preti
Paola
P
Zoppi
Annalisa
A
Derosa
Giuseppe
G
D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000627:therapeutic use*; D000843:Ankle Joint; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D004487:Edema / Q000188:drug therapy*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D011446:Prospective Studies; D013777:Tetrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan
D000959:Antihypertensive Agents; D007093:Imidazoles; D013777:Tetrazoles; D017311:Amlodipine; D000068756:Valsartan; C437965:olmesartan; D014633:Valine; D009638:Norepinephrine