Antiatherosclerotic effects of beta-blockers.
Accumulating data from studies in animals and humans indicate that beta-blockade has antiatherosclerotic effects. To date, 2 long-term ultrasound studies provide the strongest evidence. The Beta-Blocker Cholesterol-Lowering Asymptomatic Plaque Study (BCAPS) trial reported favorable effects with beta-blockade on early stages of atherosclerosis in patients with carotid plaque but no symptoms of carotid artery disease. Compared with placebo, metoprolol controlled release/extended release (CR/XL) 25 mg once daily significantly reduced plaque thickness after 18 months of treatment (net difference -0.058 mm/year; p <0.001) and at 3 years' follow-up (net difference -0.023 mm/year; p = 0.018). The Effects of Long-Term Treatment of Metoprolol CR/XL on Surrogate Variables for Atherosclerotic Disease (ELVA) trial demonstrated that beta-blockers and statins affect different mechanisms in the atherosclerotic process and have additive beneficial effects. Patients with hypercholesterolemia were randomized to metoprolol CR/XL 100 mg once daily or placebo once daily and concomitant statin therapy. The metoprolol CR/XL group had a significantly lower rate of progression of the composite carotid bulb intima-media thickness (IMT) plus common carotid IMT than the placebo group, both at 1 year (-0.08 vs -0.01 mm; p = 0.004) and after 3 years' follow-up (-0.06 vs +0.03 mm; p = 0.011). Several factors may contribute to the mechanism of benefit in these trials, including reduced sympathetic activity, improved hemodynamic parameters, and direct effects on the vascular endothelium.
Wikstrand
John
J
Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg University, Gothenburg, Sweden. john.wikstrand@wlab.gu.se
Berglund
Göran
G
Hedblad
Bo
B
Hulthe
Johannes
J
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000187:drug effects; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage; D008875:Middle Aged; D011322:Primary Prevention / Q000379:methods; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000187:drug effects; D014463:Ultrasonography
D000319:Adrenergic beta-Antagonists; D008790:Metoprolol