Last month Dr. Robert Centor, blogging ad DB's Medical Rants, expressed his approval of the new guidelines. I agree with him that we needed a more evidence based approach. But then DB makes this statement:
The brilliance of the new guidelines comes from the writing group understanding that lowering the cholesterol level does not improve important outcomes, but statins (discovered and popularized because they lower cholesterol) improve outcomes regardless of ones initial cholesterol. Other drugs that lower cholesterol or raise HDL do not improve important outcomes!
But wait a minute. There's a substantial body of research showing that lipid lowering reduces clinical events no matter how you do it. Though some of the studies have confounders, as a whole they point to the importance of LDL reduction. The Oslo study, though confounded by more smoking cessation in the intervention group, suggested a reduction in coronary events attributable to dietary reduction of cholesterol. The LRC trial showed a reduction in events attributable to LDL lowering by means of cholestyramine resin. Clinical trials of other non statin drugs also showed reduction events attributable to lipid lowering though confounded by the ability of those particular drugs to raise HDL cholesterol: the Coronary Drug Project (niacin), the WHO study (clofibrate); and the Helsinki study (gemfibrozil).
Sidebar: the Coronary Drug Project also serves as a reminder that we had comparative effectiveness research back in the 1960s. The concept is not new, only the name designed to serve political ends and give authors catchy options for their titles.
The importance of LDL in the pathogenesis of atherosclerosis has been established for a long time. Our understanding of how that works is more nuanced than it was decades ago. In our more complex understanding of atherosclerosis and new appreciation of the pleiotropic effects of statin drugs we realize more than before that the LDL concentration is not the whole story. But it remains an important part of the story.
Background: This review, though out of date for treatment recommendations, is a careful analysis of early trials establishing the lipid hypothesis and demonstrating improvement in meaningful clinical outcomes with diet and non statin drug treatments to lower cholesterol.