Comparison of the effects of losartan and atenolol on common carotid artery intima-media thickness in patients with hypertension: results of a 2-year, double-blind, randomized, controlled study.
BACKGROUND
Hypertension induces progressive pathologic changes in the arterial wall. Experimental findings suggest that these changes, which include intima-media thickening, may be mediated, at least in part, by angiotensin II (AII).


OBJECTIVE
The Losartan Vascular Regression Study (LAARS) was a double-blind, parallel-group, randomized, controlled, multicenter study designed to compare the effects of the AII antagonist losartan and the beta-blocker atenolol on ultrasonographically determined intimamedia thickness (IMT) of the common carotid artery (CCA) in patients with mild to moderate essential hypertension.


METHODS
The primary end point of the study was the yearly rate of change (YRC) from baseline of the mean IMT of the CCA (CCA-IMT(mean)) averaged over 2 years of treatment. Secondary end points included IMT of the common femoral artery and sitting systolic and diastolic blood pressures (SiSBP/SiDBP). Safety assessments of losartan and atenolol were made by statistical and clinical review of the incidence of adverse experiences as well as review of vital signs and laboratory values. A total of 414 patients with essential hypertension were screened for study inclusion at 36 study centers in Germany and Brazil. Patients received losartan (50 mg once daily) or atenolol (50 mg once daily) for 24 months. Target blood pressure (SiSBP/SiDBP <140/<90 mm Hg) was achieved by adding hydrochlorothiazide 12.5 mg once daily, doubling the dose of study drug, or adding an open-label calcium channel blocker sequentially, as needed.


RESULTS
Of the original 414 patients screened, 280 hypertension patients (SiDBP 95-115 mm Hg), aged 35 to 65 years, with an IMT of 0.8 to 1.5 mm of the right or left CCA, were randomized to treatment with either losartan (n = 142) or atenolol (n = 138). Both losartan and atenolol therapy produced comparable reductions in CCA-IMTmean over 24 months compared with baseline; the average YRC was -0.038 +/- 0.004 mm/y (P < or = 0.001) for losartan and -0.037 +/- 0.004 mm/y (P < or = 0.001) for atenolol. There were no significant differences between groups. Losartan showed a greater reduction of femoral artery IMT than did atenolol; the average YRC was -0.024 mm/y (P < or = 0.05) for losartan and -0.017 mm/y for atenolol (P = NS), with no significant difference between groups. Both agents produced similar significant reductions in SiSBP and SiDBP and were generally well tolerated. Approximately 7% of losartan patients had drug-related clinical adverse events, compared with 12% of atenolol patients.


CONCLUSIONS
The findings of LAARS, the first large study with an AII antagonist that examined IMT, suggest that AII antagonism reverses the early stages of vascular hypertrophy in patients with hypertension. Further studies are needed to delineate the relative importance of AII antagonism versus blood pressure reduction per se in mediating the beneficial vascular effects of losartan.
Ludwig
Malte
M
University Clinic Bonn, Department of Medicine, Germany.
Stapff
Manfred
M
Ribeiro
Artur
A
Fritschka
Emanuel
E
Tholl
Ulrich
U
Smith
Ronald D
RD
Stumpe
Klaus O
KO
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001262:Atenolol / Q000494:pharmacology* / Q000627:therapeutic use*; D017536:Carotid Artery, Common / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D017540:Tunica Media / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology
D000959:Antihypertensive Agents; D001262:Atenolol; D019808:Losartan