Changes in cardiovascular risk factors by combined pharmacological and nonpharmacological strategies: the main results of the CELL Study. Atorvastatin for the treatment of mild to moderate Alzheimer disease: preliminary results.
The objectives of the Cost Effectiveness of Lipid Lowering (CELL) study were twofold: (i) to evaluate the effect on overall cardiovascular risk of two types of health care advice ("usual' and "intensive') given in primary care, with or without pharmacological medication, with the target being to attain a moderate decrease in cholesterol; (ii) to evaluate the ritual of daily medication on compliance with the health care advice.
                A prospective, double-blind, randomized, controlled trial of 18 months' duration.
                The study was carried out in 32 health centres (out of a total of approximately 850) in Sweden.
                In all, 681 subjects, aged 30-59 years, were randomized. They had at least two cardiovascular risk factors in addition to moderate primary hyperlipidaemia (total cholesterol of at least 6.50 mmol L-1 on three occasions measured by Reflotron triglycerides less than 4.0 mmol L-1 and an LDL:HDL cholesterol ratio of more than 4.0). Most (87%) of the subjects were males; 626 subjects (92%) completed the 18-month follow-up.
                Half the subjects were randomized to 'intensive advice' given in group sessions led by doctors and nurses in primary care. The other half received 'usual advice'. In each of the two advice groups, one-third received an active lipid-lowering drug (pravastatin), one-third placebo, and one-third no drug at all. The tablets were titrated to achieve a 15% reduction in cholesterol.
                Changes in the overall Framingham risk score, and the development of adverse events in each group.
                The change in Framingham risk score was significantly reduced only in subjects taking lipid-lowering medication (together with intensive advice -0.13; 95% CI-0.20, -0.06, and together with usual advice -0.16; 95% CI -0.23, -0.09). The other subjects receiving intensive advice tended to fare better than those on usual advice. Lifestyle was not influenced significantly over the study period. The ritual of daily medication did not affect the outcome.
                As expected, lipid-lowering medication reduced serum cholesterol as well as overall cardiovascular risk in subjects with several risk factors for cardiovascular disease. There was no additive effect of intensive advice to these subjects. However, there was a meagre but significant effect of intensive advice in subjects not receiving active lipid-lowering drugs. One explanation for this difference may be that those on active lipid-lowering medication who had substantial drops in cholesterol might have felt less inclined to change their lifestyle compared with those on other treatment regimens who had less successful drops in cholesterol. There was no benefit from the ritual of taking daily medication. Laboratory evidence of cholesterol-induced production of amyloid beta as a putative neurotoxin precipitating Alzheimer disease, along with epidemiological evidence, suggests that cholesterol-lowering statin drugs may favorably influence the progression of the disorder.
                To determine if treatment with atorvastatin calcium affects the cognitive and/or behavioral decline in patients with mild to moderate Alzheimer disease.
                Pilot intention-to-treat, proof-of-concept, double-blind, placebo-controlled, randomized (1:1) trial with a 1-year exposure to once-daily atorvastatin calcium (80 mg; two 40-mg tablets) or placebo using last observation carried forward analysis of covariance as the primary method of statistical assessment.
                Individuals with mild to moderate Alzheimer disease (Mini-Mental State Examination score of 12-28) were recruited. Of the 98 participants providing informed consent, 71 were eligible for randomization, 67 were randomized, and 63 subjects completed the 3-month visit and were considered evaluable.
                The primary outcome measures were change in Alzheimer's Disease Assessment Scale-cognitive subscale and the Clinical Global Impression of Change Scale scores. The secondary outcome measures included scores on the Mini-Mental State Examination, Geriatric Depression Scale, the Neuropsychiatric Inventory Scale, and the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory. The tertiary outcome measures included total cholesterol, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol levels.
                Atorvastatin reduced circulating cholesterol levels and produced a positive signal on each of the clinical outcome measures compared with placebo. This beneficial effect reached significance for the Geriatric Depression Scale and the Alzheimer's Disease Assessment Scale-cognitive subscale at 6 months and was significant at the level of a trend for the Alzheimer's Disease Assessment Scale-cognitive subscale, Clinical Global Impression of Change Scale, and Neuropsychiatric Inventory Scale at 12 months assessed by analysis of covariance with last observation carried forward.
                Atorvastatin treatment may be of some clinical benefit and could be established as an effective therapy for Alzheimer disease if the current findings are substantiated by a much larger multicenter trial.
Data from three clinical trials assessing ALE for treating hypercholesterolaemia are available. Athough the trials are of adequate methodological quality they have some shortcomings and one is available as abstract only. There is an indication that ALE has potential in lowering cholesterol levels, but the evidence is, as yet, not convincing. The limited data on safety suggest only mild, transient and infrequent adverse events with the short term use of ALE.