Beyond Endorsed Lipid Lowering With EBT Scanning - BELLES

Description:

The goal of the BELLES trial was to evaluate the effect of aggressive versus moderate lipid-lowering therapy on vascular calcification among hypercholesterolemic post-menopausal women.

Hypothesis:

Aggressive lipid-lowering therapies may be more effective than moderate lipid-lowering therapies for slowing vascular calcification in post-menopausal hypercholesterolemic.

Study Design

Study Design:

Patients Screened: 4739
Patients Enrolled: 615
Mean Follow Up: 12 months
Mean Patient Age: Mean age 64 years
Female: 100

Patient Populations:

Post-menopausal women age 55-75 years; LDL cholesterol ≥ 130 mg/dL for women with CHD, CHD risk equivalents, or ≥2 risk factors and a 10-year CHD risk of 10-20%; LDL ≥160 mg/dL for patients with ≥2 CHD risk factors and 10-year CHD risk of <10%; or patients with 0 to 1 risk factors; total CVS ≥30 at baseline.

Exclusions:

Known contraindication to the use of statins, such as known hypersensitivity or hepatic dysfunction with aspartate transaminase (AST) or alanine transaminase (ALT) levels ≥1.5 times the upper limit of normal; use of lipid-lowering drugs other than HRT within 3 months of screening; evidence of secondary hyperlipidemia, renal dysfunction, uncontrolled type 1 or type 2 diabetes mellitus, myocardial infarction <6 months, uncontrolled hypothyroidism, and plasma triglyceride levels >600 mg/dL.

Primary Endpoints:

Percent change from baseline to 12 month in total coronary calcium volume score on EBT.

Secondary Endpoints:

Percent change from baseline to 12 month in total cholesterol, LDL cholesterol, HDL cholesterol, apolipoprotein B, and triglyceride

Absolute change in total CVS and percent change and absolute change from baseline to 12 month in coronary CVS in each vessel.

Drug/Procedures Used:

Women with hyperlipidemia were randomized in a double-blind manner to intensive (atorvastatin 80 mg/d; n=305) or moderate (pravastatin 40 mg/d; n=309) lipid-lowering therapy. Patients underwent electron-beam tomography (EBT) at baseline and 12 month follow-up to measure change in calcium volume score.

Principal Findings:

475 of the 615 women in the trial had complete follow-up. Post-menopausal status was established in 68% of women, with the remaining 32% had hysterectomy. Hormone replacement therapy was used in 23.6% of patients. Compared to baseline LDL levels were 46.6% (to 82 mg/dL) and 24.5% (to 129 mg/dL) reduced in the intensive and moderate treatment arms, respectively (p<0.0001 vs pravastatin). Reductions in total cholesterol were greater in the atorvastatin group (-33.8% to 176.2 mg/dL vs -17.2% to 219.5 mg/dL, p<0.0001), as were reductions in triglycerides (-21.5% to 135.5 mg/dL vs -9.1% to 150.5 mg/dL, p<0.0001). The National Cholesterol Education Program Adult Treatment Panel III LDL goal was met in more patients in the intensive group compared with the moderate group (85.3% vs 58.8%, p<0.0001).

Percent change from baseline in total calcium volume score did not differ between the two treatment groups (median 15.1% for atorvastatin and 14.3% for pravastatin, p=0.64). Likewise, the absolute change did not differ (median 14.2 vs 18.5, respectively, p=0.21). Single-artery calcium volume score also did not differ between groups for absolute or relative change (p=NS). CVS progression trended greater in women with prior cardiovascular disease, diabetes mellitus, and hypertension, but hormone replacement therapy had no effect on progression.

Clinically important ALT and AST elevations occurred in 2.7% of the atorvastatin group and no patients in the pravastatin group. here was one case of rhabdomyolysis in the atorvastatin arm.

Interpretation:

Among hypercholesterolemic post-menopausal women, treatment with an intensive lipid-lowering strategy with atorvastatin was not associated with changes in progression of coronary calcium volume score on EBT at 12 months compared with a moderate lipid-lowering strategy with pravastatin. The lack of benefit in vascular calcification occurred despite lower lipid parameters in the atorvastatin group. The recent REVERSAL trial demonstrated a reduction in IVUS-assessed atheroma volume with an aggressive lipid-lowering strategy with atorvastatin compared with a more moderate lipid-lower strategy with pravastatin among patients with symptomatic CAD and elevated LDL. The authors speculate that the differences in the results may be due to the greater ability to detect a difference with IVUS technology compared with EBT or the lower risk population studied in the present trial.

References:

Raggi P, et al. Aggressive Versus Moderate Lipid-Lowering Therapy in Hypercholesterolemic Postmenopausal Women. Beyond Endorsed Lipid Lowering With EBT Scanning (BELLES). Circulation. 2005;112:.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Noninvasive Imaging, Prevention, Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Hypertension

Keywords: Follow-Up Studies, Plaque, Atherosclerotic, Cholesterol, LDL, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Risk Factors, Heptanoic Acids, Hypercholesterolemia, Rhabdomyolysis, Pyrroles, Tomography, Vascular Calcification, Pravastatin, Hysterectomy, Triglycerides, Hormone Replacement Therapy, Hypertension, Diabetes Mellitus


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