Therapy with a class of drugs called statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, has been shown to reduce risk of stroke in patients with cardiovascular disease. HMG CoA reductase catalyzes an irreversible step in the cholesterol synthesis pathway shown in Figure 1 below. Statins block cholesterol synthesis by inhibiting the conversion of glucose and fatty acid metabolic byproducts to cholesterol in the liver. Another cholesterol-lowering agent, nicotinic acid, limits the mobilisation of fatty acids from peripheral tissues.
Figure 1. Cholesterol Synthesis Pathway
Cholesterol exceeding hepatic requirements is transported in the bloodstream via low density lipoproteins (LDL), whose production is positively correlated with that of cholesterol. LDL is associated with cardiovascular disease at levels greater than 100 mg/dl.
A recent study investigated the use of statins in stroke prevention in patients without cardiovascular disease, with a history of previous stroke. Subjects were randomly assigned to four treatment groups: placebo, nicotinic acid, high-dose atorvastatin, or both nicotinic acid and high-dose atorvastatin. Primary outcome measures included serum LDL levels and number of strokes occurring during the study period.
Four thousand patients were followed for six years. The patients’ diet was unchanged. Outcome indicators for the study are presented in Table 1 below.
Table 1. Outcome monitoring
Mean Serum LDL
|Number of Strokes |
|Group A ||145||73 ||205 |
|Group B||134 ||135 ||262|
|Group C||139 ||132 ||257 |
|Group D ||140 ||62 ||203 |