Lipid-lowering agents clinical trials

In rodent stroke models, statin pretreatment has been shown to reduce infarct volumes and improve outcomes. Similarly, several clinical studies have shown that prior statin use reduced the severity of acute ischemic stroke and myocardial infarction. Recent studies indicate that beneftt can be achieved even when treatment is initiated after the onset of symptoms. In rodents, atorvastatin and simvastatin have been shown to reduce the growth of ischemic lesions, enhance functional outcome, and induce brain plasticity when administered after stroke onset. A retrospective analysis of the population-based Northern Manhattan Stroke Study (NOMASS) showed that patients using lipid-lowering agents at the time of ischemic stroke have a lower incidence of in-hospital stroke progression and reduced 90-day mortality rates. Retrospective analysis of data of the phase III citicoline trial showed... 

Consequences also can be discussed in terms of intermediate and final outcomes. Intermediate outcomes can serve as a proxy for more relevant final outcomes. For example, achieving a decrease in low-density lipoprotein cholesterol levels with a lipid-lowering agent is an intermediate consequence that may serve as a proxy for a more final outcome such as a decrease in myocardial infarction rate. Intermediate consequences are used commonly in clinical and pharmacoeconomic analyses as proxies predictive of final outcomes because their use reduces the cost and time required to conduct a trial. 

In vitro, allicin and related compounds inhibit HMG-CoA reductase, which is involved in cholesterol biosynthesis (see Chapter 35 Agents Used in Hyperlipidemia). Several clinical trials have investigated the lipid-lowering potential of garlic. Some have shown significant reductions in cholesterol and others no effect. The most recent meta-analysis suggested a minor (5%) reduction of total cholesterol that was insignificant when dietary controls were in place. 

Helsinki Heart Study (15) have all demonstrated the benefit of lipid lowering using various hypolipidemic agents for prevention of initial cardiac events. Secondary prevention trials have unequivocally shown that lipid lowering therapy not only reduces acute coronary events and other clinical endpoints, but also results in angiographic improvement. These studies have used different classes of drugs (statins, fibrates, niacin, bile acid resins—alone and in combination) in both hyper- and normo-cholesterolemic patients with established CAD. 

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