Effects of losartan and atenolol on left ventricular mass and neurohormonal profile in patients with essential hypertension and left ventricular hypertrophy.
OBJECTIVE
To compare the effects of the angiotensin II antagonist, losartan, with those of atenolol on left ventricular hypertrophy (LVH), blood pressure and neurohormone concentrations in hypertensive patients with LVH.


METHODS
A multinational, randomized, double-blind trial.


METHODS
Hospital.


METHODS
Hypertensive patients with an echocardiographically documented left ventricular mass index (LVMI) 120 g/m(2) (men) or 105 g/m(2) (women).


METHODS
Patients allocated randomly to groups received either losartan or atenolol 50 mg/day for 36 weeks, with possible titration to 100 mg/day, and addition of hydrochlorothiazide 12.5 or 25 mg/day.


METHODS
Changes in LVMI and sitting systolic (SBP) and diastolic (DBP) blood pressures after 36 weeks of treatment (study powered for non-inferiority hypothesis). All echocardiographic data were read in a central laboratory by staff blinded to the treatments and sequence of echocardiographic tapes.


RESULTS
The estimated treatment difference between the losartan and atenolol regimens (mean change from baseline at week 36) in LVMI was -2.5 g/m(2) [95% confidence interval (CI) -7.36 to 2.37 g/m(2) ] in favor of losartan, indicating that losartan was significantly non-inferior ( 0.001, non-inferiority limit 8 g/m(2) ) and numerically superior to atenolol in reducing LVMI. The losartan-based regimen significantly reduced LVMI after 36 weeks compared with baseline (-6.56 g/m(2) , 95% CI -10.24 to -2.88 g/m(2) , P<0.001), whereas the atenolol-based regimen had no significant effect (-3.71 g/m, 95% CI -7.75 to 0.32 g/m(2) , P= NS). In a subset of 82 patients, significant changes in serum concentrations of atrial natriuretic peptide, brain natriuretic peptide and immunoreactive amino-terminal pro-brain natriuretic peptide were recorded in losartan-treated ( 0.01) but not atenolol-treated patients. Losartan and atenolol significantly decreased SBP and DBP from baseline after 6, 12, 24 and 36 weeks. The changes from baseline in DBP were greater in the atenolol group at weeks 6 and 36 [difference -2.6 mmHg ( P= 0.016) at week 36]. However, both treatment regimens achieved similar SBP/DBP values at week 36 (141.1 +/- 12.8/86.8 +/- 8.2 mmHg for losartan and 141.4 +/- 17.2/85.0 +/- 10.1 mmHg for atenolol, respectively). Overall, losartan treatment was associated with significantly fewer drug-related clinical adverse events, compared with atenolol (10 and 22%, respectively, P= 0.028).


CONCLUSIONS
Both losartan- and atenolol-based regimens effectively decreased blood pressure. Losartan was non-inferior and numerically superior to atenolol in regression of LVH. The reduction in hypertrophy with losartan treatment was accompanied by reductions in circulating concentrations of cardiac natriuretic peptides. Losartan, by specifically blocking angiotensin II, may therefore have effects on the heart beyond those expected from the decrease in blood pressure alone. Losartan was better tolerated than atenolol.
Dahlof
Björn
B
University of Göteborg-Ostra University Hospital, Göteborg, Sweden. bdahlof@scandanaviancri.se
Zanchetti
Alberto
A
Diez
Javier
J
Nicholls
M Gary
MG
Yu
Cheuk-Man
CM
Barrios
Vivencio
V
Aurup
Peter
P
Smith
Ronald D
RD
Johansson
Magnus
M
D000368:Aged; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001262:Atenolol / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004452:Echocardiography; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging* / Q000209:etiology; D019808:Losartan / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018377:Neurotransmitter Agents / Q000097:blood*; D012449:Safety
D000959:Antihypertensive Agents; D018377:Neurotransmitter Agents; D001262:Atenolol; D019808:Losartan