Beta-Blocker Cholesterol-Lowering Asymptomatic Plaque Study - BCAPS

Description:

The Beta-Blocker Cholesterol-Lowering Asymptomatic Plaque Study (BCAPS) was a randomized, double-blind, placebo-controlled trial designed to assess the effects of low-dose, once-daily metoprolol and fluvastatin on the progression of carotid intima-media thickness (IMT) in patients with carotid plaque without symptoms of carotid artery disease.

Hypothesis:

Compared to placebo, treatment with metoprolol and fluvastatin would be associated with reduced rates of progression of carotid IMT.

Study Design

Study Design:

Patients Screened: 1,548
Patients Enrolled: 793
Mean Follow Up: 36 months
Mean Patient Age: mean 62
Female: 55

Patient Populations:

Men and women age 49 to 70 with plaque in the right carotid artery, but with no symptoms of carotid artery disease (participants for the trial were from the Malmö Diet and Cancer cohort)

Exclusions:

History of MI, angina pectoris, or stroke within the preceding three months; history of surgical intervention in the right carotid artery; regular use of beta-blockers or statins; blood pressure >160 (systolic) or 95 (diastolic) mm Hg; total cholesterol >309 mg/dl; hyperglycemia suspected to require insulin treatment; or conditions that in the opinion of the investigator rendered the subject unsuitable for the trial

Primary Endpoints:

Change in mean IMT in the common carotid artery (10-mm-long section) and change in maximum IMT in the carotid bulb at 36 months

Secondary Endpoints:

Adverse events, laboratory findings (lipid panels, liver function tests), mortality, incidence of myocardial infarction (MI), and stroke

Drug/Procedures Used:

Four arms: placebo/placebo, metoprolol CR/XL 25 mg orally (po) daily plus placebo, placebo plus fluvastatin 40 mg po daily, and metoprolol CR/XL 25 mg plus fluvastatin 40 mg

Concomitant Medications:

Patients who developed high serum cholesterol or high triglycerides during the trial were recommended to follow a low-fat diet, and if evidence of high cholesterol values persisted, these subjects were referred to an independent blinded specialist of lipid disorders. Twenty-two of these subjects were prescribed open lipid-lowering therapy. Other conditions, such as high blood pressure, congestive heart failure, or abnormal laboratory values during the trial, were dealt with in accordance with existing guidelines.

Principal Findings:

The study groups were well-balanced with respect to baseline characteristics. Fluvastatin-treated patients had lowered total and low-density lipoprotein cholesterol levels (no change in placebo group), and serum triglycerides increased 20% in the metoprolol CR/XL-treated groups (similar to the placebo group). Metoprolol CR/XL-treated patients had lower heart rates compared to the placebo/placebo group, but no significant difference in blood pressures.

Fluvastatin, but not metoprolol CR/XL, was associated with a decreased rate of progression of mean IMT of the common carotid artery compared with placebo at 36 months (mean difference between groups of -0.009 mm/year, p=0.002). Metoprolol CR/XL, but not fluvastatin, was associated with a slowed rate of progression of maximum IMT of the carotid bulb compared to placebo at 18 and 36 months (mean difference between groups of -0.058 mm/year, p=0.004 at 18 months and -0.023 mm/year, p=0.014 at 36 months). The combined endpoint of all-cause mortality and a cardiovascular event (time to first event) was significantly lower in patients treated with metoprolol CR/XL (8 vs. 19 patients for comparison vs. placebo, p=0.031).

Interpretation:

In this randomized clinical trial in asymptomatic patients with carotid plaque, treatment with a low-dose beta-blocker, metoprolol CR/XL, was associated with slowed progression of carotid bulb IMT, and treatment with fluvastatin was associated with slowed progression of common carotid IMT. This is the first study to demonstrate an association between treatment with beta-blockers and slowed progression of atherosclerosis. Although the measured effects were mild, this study is nonetheless hypothesis-generating insofar as it suggests that beta-blockade (in low doses) can attenuate the progression of plaque growth.

References:

Hedblad B, Wikstrand J, Janzon L, Wedel H, Berglund G. Low-dose metoprolol CR/XL and fluvastatin slow progression of carotid intima-media thickness: main results from the Beta-Blocker Cholesterol-Lowering Asymptomatic Plaque Study (BCAPS). Circulation 2001;103:1721-6.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Noninvasive Imaging, Prevention, Vascular Medicine, Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Echocardiography/Ultrasound, Diet

Keywords: Atherosclerosis, Carotid Intima-Media Thickness, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Fatty Acids, Monounsaturated, Hypercholesterolemia, Heart Rate, Lipoproteins, LDL, Cholesterol, Indoles, Diet, Metoprolol, Carotid Stenosis, Triglycerides


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