Effect of Controlled Release/Extended Release Metoprolol on Carotid Intima-Media Thickness in Patients With Hypercholesterolemia

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Abstract
Background and Purpose — β-Adrenergic blockade has in several studies been shown to improve survival after myocardial infarction. In animal experiments β-blockers have also shown an antiatherosclerotic effect. The aim of this study was to test the hypothesis that the β-blocker metoprolol succinate controlled release/extended release (CR/XL), when given to patients with hypercholesterolemia on concomitant lipid-lowering therapy, provides an additional antiatherosclerotic effect to that provided by the statins, measured as carotid intima-media thickness (IMT). Methods — We conducted a randomized, double-blind, placebo-controlled, single center trial to compare the effect of metoprolol CR/XL (100 mg once daily) and placebo on the progression of carotid IMT during 36 months of treatment in patients with hypercholesterolemia and signs of early atherosclerosis in the carotid artery. Most patients were prescribed lipid-lowering treatment with statins. Results — A highly significant difference in the progression rate of the composite variable of carotid bulb IMT+common carotid IMT was observed between the metoprolol CR/XL and placebo groups after 1 year of treatment (−0.08 versus −0.01 mm; P =0.004), an effect that was sustained after 3 years of follow-up (−0.06 versus +0.03 mm; P =0.011). The patients had high levels of total cholesterol at randomization: 9.4 mmol/L in the metoprolol CR/XL group and 8.6 mmol/L in the placebo group. During the study the 2 randomization groups were treated with lipid-lowering drugs, mainly statins, to a similar extent, and total cholesterol was reduced to 6.4 mmol/L at end of follow-up in both groups. Conclusions — The results from the present study in patients with hypercholesterolemia under concomitant lipid-lowering therapy are the first clinical data to show an antiatherosclerotic effect of β-blockade as additional therapy to statins. The data indicate that statin treatment and treatment with β-blockers affect different mechanisms in the atherosclerotic process and have additive beneficial effects.