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Effect of Aggressive Versus Conventional Lipid Lowering on Atherosclerosis Progression in Familial Hypercholesterolemia - ASAP
Description:
The ASAP was a randomized, double-blind, prospective clinical trial designed to assess whether aggressive cholesterol lowering with statins was more effective than conventional statin treatment in patients with familial hypercholesterolemia.
Hypothesis:
In patients with familial hypercholesterolemia, aggressive low-density lipoprotein cholesterol (LDL-C) lowering would slow atherosclerosis progression, as measured by carotid intima-media thickness (IMT).
Study Design
Study Design:
Patients Screened: N/A
Patients Enrolled: 325
NYHA Class: N/A
Mean Follow Up: Two years
Mean Patient Age: 30-70
Female: N/A
Mean Ejection Fraction: N/A
Patient Populations:
Men and women aged 30-70 years with familial hypercholesterolemia who were either previously untreated or treated, but with LDL-C concentrations remaining around 4.5 mmol/l were eligible for the study.
Exclusions:
N/A
Primary Endpoints:
The primary endpoint was established as the change in millimeters in mean IMT after 24 months.
Secondary Endpoints:
Secondary endpoints included the percentage change from baseline in lipid indices: total cholesterol, calculated LDL-C, HDL-C, triglycerides, apolipoprotein B-100, and lipoprotein (a).
Drug/Procedures Used:
Patients with familial hypercholesterolemia were given either atorvastatin 80 mg or simvastatin 40 mg daily, on an intention-to-treat basis. Baseline characteristics and medical history were recorded at baseline. Subsequent visits were planned after four weeks, six weeks, and every 12 weeks thereafter.
At each visit, a brief physical examination was done, tablets were counted, and standard dietary instruction was given. In both groups, lipids, lipoproteins, and safety laboratory measurements were also done at each visit. Carotid ultrasound examinations were done at baseline and at one and two years.
Concomitant Medications:
The use of concomitant treatments was left to the discretion of the participating investigators.
Principal Findings:
A total of 325 patients were enrolled (160 in the atorvastatin group and 165 in the simvastatin group) and 280 patients completed the study. At baseline, lipid and lipoprotein concentrations did not differ between treatment groups. The IMTs of the common carotid artery, carotid bifurcation, and internal carotid artery were equally distributed between treatment groups.
After treatment with atorvastatin for two years, IMT decreased (-0.031 mm, 95% confidence interval [CI] -0.007 to -0.055, p=0.0017), whereas in the simvastatin group, it increased (0.036, 95% CI 0.014 to 0.058, p=0.0005). The change in thickness differed significantly between the two groups (p=0.0001). Regression of the IMT was seen in 106/160 (66%) vs. 69/165 (42%) patients in the atorvastatin and simvastatin groups, respectively.
High-density lipoprotein cholesterol (HDL-C) increased in both treatment groups by about 13%. Atorvastatin reduced triglyceride concentration by 29%, and simvastatin did so by 18%. LDL-C was reduced by 50.5% in the atorvastatin group and by 41.2% in the simvastatin group. Both drugs were equally well tolerated.
Interpretation:
Among patients with familial hypercholesterolemia, aggressive LDL-C reduction by atorvastatin was associated with regression of the carotid intima thickness, whereas conventional LDL lowering was not.
References:
Smilde TJ, van Wissen S, Wollersheim H, Trip MD, Kastelein JJ, Stalenhoef AF. Effect of aggressive versus conventional lipid lowering on atherosclerosis progression in familial hypercholesterolemia (ASAP): a prospective, randomised, double-blind trial. Lancet 2001;357:577-81.
Keywords: Atherosclerosis, Carotid Intima-Media Thickness, Hyperlipoproteinemia Type II, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Lipids, Coronary Disease, Heptanoic Acids, Simvastatin, Carotid Artery, Internal, Pyrroles, Cholesterol, Intention to Treat Analysis, Triglycerides, Physical Examination
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