Calcium antagonist lacidipine slows down progression of asymptomatic carotid atherosclerosis: principal results of the European Lacidipine Study on Atherosclerosis (ELSA), a randomized, double-blind, long-term trial.
BACKGROUND
Most cardiovascular events associated with hypertension are complications of atherosclerosis. Some antihypertensive agents influence experimental models of atherosclerosis through mechanisms independent of blood pressure lowering.


RESULTS
The European Lacidipine Study on Atherosclerosis (ELSA) was a randomized, double-blind trial in 2334 patients with hypertension that compared the effects of a 4-year treatment based on either lacidipine or atenolol on an index of carotid atherosclerosis, the mean of the maximum intima-media thicknesses (IMT) in far walls of common carotids and bifurcations (CBM(max)). This index has been shown by epidemiological studies to be predictive of cardiovascular events. A significant (P<0.0001) effect of lacidipine was found compared with atenolol, with a treatment difference in 4-year CBM(max) progression of -0.0227 mm (intention-to-treat population) and -0.0281 mm (completers). The yearly IMT progression rate was 0.0145 mm/y in atenolol-treated and 0.0087 mm/y in lacidipine-treated patients (completers, 40% reduction; P=0.0073). Patients with plaque progression were significantly less common, and patients with plaque regression were significantly more common in the lacidipine group. Clinic blood pressure reductions were identical with both treatments, but 24-hour ambulatory systolic/diastolic blood pressure changes were greater with atenolol (-10/-9 mm Hg) than with lacidipine (-7/-5 mm Hg). No significant difference between treatments was found in any cardiovascular events, although the relative risk for stroke, major cardiovascular events, and mortality showed a trend favoring lacidipine.


CONCLUSIONS
The greater efficacy of lacidipine on carotid IMT progression and number of plaques per patient, despite a smaller ambulatory blood pressure reduction, indicates an antiatherosclerotic action of lacidipine independent of its antihypertensive action.
Zanchetti
Alberto
A
University of Milan, Ospedale Maggiore, Istituto Auxologico Italiano, Milan, Italy. zanchett@mailserver.unimi.it
Bond
M Gene
MG
Hennig
Michael
M
Neiss
Albrecht
A
Mancia
Giuseppe
G
Dal Palù
Cesare
C
Hansson
Lennart
L
Magnani
Bruno
B
Rahn
Karl-Heinz
KH
Reid
John L
JL
Rodicio
Josè
J
Safar
Michel
M
Eckes
Lothar
L
Rizzini
Paolo
P
D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000494:pharmacology*; D001262:Atenolol / Q000009:adverse effects / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000187:drug effects; D002340:Carotid Artery Diseases / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D004095:Dihydropyridines / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D013995:Time; D016896:Treatment Outcome; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000187:drug effects; D017540:Tunica Media / Q000000981:diagnostic imaging / Q000187:drug effects; D014463:Ultrasonography
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C060285:lacidipine; D001262:Atenolol