Short term essential fatty acid deficiency in rats. Influence of dietary carbohydrates.

International audienceThe effects of long term (8-14 wk) essential fatty acid (EFA)-deprived diets in rats are well documented. In the present study, we compared, in weanling rats, the effect of a short term (two wk) hydrogenated coconut oil, EFA-deprived, diet (D) with that of a corn oil, EFA-adequate, diet (A), using either sucrose (SU) or starch (ST) as carbohydrate. After two wk, rats fed the sucrose/hydrogenated coconut oil diet developed some characteristic features of EFA deprivation: slower growth rate, decreases in linoleic and arachidonic acid of plasma phospholipids and an increase in n-9 eicosatrienoic acid of plasma phospholipids. When rats ate the starch/hydrogenated coconut oil diet, there was a similar decrease in linoleic acid of plasma phospholipids, but only a small effect on growth rate and no change in the arachidonic acid content of plasma phospholipids. EFA deprivation and sucrose had opposite effects on plasma triglyceride (TG) levels: deprivation induced a decrease, whereas the sucrose induced an increase in very low density lipoprotein (VLDL) triglycerides. The observed decrease in plasma triglyceride during EFA deprivation might result from an activation of lipoprotein lipase during the early stages of deprivation

A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee

Many clinical trials have evaluated the benefit of long-term use of antiplatelet drugs in reducing the risk of clinical thrombotic events. Aspirin and ticlopidine have been shown to be effective, but both have potentially serious adverse effects. Clopidogrel, a new thienopyridine derivative similar to ticlopidine, is an inhibitor of platelet aggregation induced by adenosine diphosphate. METHODS: CAPRIE was a randomised, blinded, international trial designed to assess the relative efficacy of clopidogrel (75 mg once daily) and aspirin (325 mg once daily) in reducing the risk of a composite outcome cluster of ischaemic stroke, myocardial infarction, or vascular death; their relative safety was also assessed. The population studied comprised subgroups of patients with atherosclerotic vascular disease manifested as either recent ischaemic stroke, recent myocardial infarction, or symptomatic peripheral arterial disease. Patients were followed for 1 to 3 years. FINDINGS: 19,185 patients, with more than 6300 in each of the clinical subgroups, were recruited over 3 years, with a mean follow-up of 1.91 years. There were 1960 first events included in the outcome cluster on which an intention-to-treat analysis showed that patients treated with clopidogrel had an annual 5.32% risk of ischaemic stroke, myocardial infarction, or vascular death compared with 5.83% with aspirin. These rates reflect a statistically significant (p = 0.043) relative-risk reduction of 8.7% in favour of clopidogrel (95% Cl 0.3-16.5). Corresponding on-treatment analysis yielded a relative-risk reduction of 9.4%. There were no major differences in terms of safety. Reported adverse experiences in the clopidogrel and aspirin groups judged to be severe included rash (0.26% vs 0.10%), diarrhoea (0.23% vs 0.11%), upper gastrointestinal discomfort (0.97% vs 1.22%), intracranial haemorrhage (0.33% vs 0.47%), and gastrointestinal haemorrhage (0.52% vs 0.72%), respectively. There were ten (0.10%) patients in the clopidogrel group with significant reductions in neutrophils (< 1.2 x 10(9)/L) and 16 (0.17%) in the aspirin group. INTERPRETATION: Long-term administration of clopidogrel to patients with atherosclerotic vascular disease is more effective than aspirin in reducing the combined risk of ischaemic stroke, myocardial infarction, or vascular death. The overall safety profile of clopidogrel is at least as good as that of medium-dose aspirin