Search for lower cholesterol proves positive

Although more potent cholesterol reduction has previously been linked with a reduction in cardiovascular events (the ‘lower is better’ paradigm), concerns have remained about the safety of using high doses of cholesterol-lowering medications to this end. The Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) aimed to establish more reliably the balance between efficacy and safety of intensive low-density lipoprotein (LDL) lowering.

Six thousand and thirty-one participants were randomly assigned to 80 mg simvastatin daily and 6033 to 20 mg simvastatin daily. Over an average of 6.7 years of follow-up, simvastatin 80 mg was noted to give an average of 0.35 mmol/l greater reduction in LDL-cholesterol compared with allocation to 20 mg. A 6% further reduction in vascular events was seen due to this reduction in LDL-cholesterol, consistent with what has been noted in other statin trials. Although there were no significant differences in the number of haemorrhagic strokes or non-vascular deaths, there were more cases of myopathy in the 80 mg group (0.9% vs 0.03%).