Antiatherosclerotic effects of β-blockers

Accumulating data from studies in animals and humans indicate that β-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 β-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 β-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.