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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Effect of aggressive versus conventional lipid lowering on atherosclerosis progression in familial hypercholesterolaemia (ASAP): a prospective, randomised, double-blind trial.

BACKGROUND: High LDL-cholesterol is a risk factor for atherosclerosis. We aimed to determine whether aggressive cholesterol lowering with statins was more effective than conventional statin treatment in this disease. We investigated the effect of high-dose atorvastatin on carotid atherosclerosis progression. METHOD: We did a randomised, double-blind clinical trial in 325 patients with familial hypercholesterolaemia. Patients were given either atorvastatin 80 mg (n=160) or simvastatin 40 mg (n=165) daily, on an intent-to-treat basis. The primary endpoint was the change of carotid intima media thickness (IMT), as measured by quantitative B-mode ultrasound, over 2 years. FINDINGS: The overall baseline IMT, combining the measurements of the common and internal carotid artery and the carotid bifurcation on both sides, was 0.93 mm (SD 0.22) and 0.92 mm (0.21) in the atorvastatin and simvastatin groups, respectively. After treatment with atorvastatin for 2 years, IMT decreased (-0.031 mm [95% CI -0.007 to -0.055]; p=0.0017), whereas in the simvastatin group it increased (0.036 [0.014-0.058]; p=0.0005). The change in thickness differed significantly between the two groups (p=0.0001). Atorvastatin showed greater reductions in cholesterol concentrations than did simvastatin. HDL-cholesterol concentrations increased in both groups. Both drugs were equally well tolerated. INTERPRETATION: Our results show that aggressive LDL-cholesterol reduction by atorvastatin was accompanied by regression of carotid intima media thickness in patients with familial hypercholesterolaemia, whereas conventional LDL lowering was not.[1]


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