LDL reduction matters

Given recent enthusiasm for the pleiotrophic effects of statins as well as controversy regarding the appropriate goal for LDL cholesterol reduction, a paper in the American Journal of Cardiology (AJC) entitled Low-Density Lipoprotein Cholesterol Reduction: The End Is More Important Than the Means seems timely. The paper reviews multiple lipid lowering trials which show that the more one lowers LDL cholesterol the greater the cardiovascular risk reduction, regardless of the means used to do it.

Moreover, it cited this meta-regression analysis which raised questions about the pleiotrophic effects of statins, concluding:

The pleiotropic effects of statins do not seem to contribute an additional cardiovascular risk reduction benefit beyond that expected from the degree of LDL-C lowering observed in other trials that primarily lowered LDL-C.

Multiple means of LDLC reduction, whether via statins, ileal bypass surgery, diet or binding resins were associated with similar reductions in risk for a given degree of LDLC reduction.

The AJC paper also synthesized the strong data from multiple trials in support of newer aggressive LDLC targets (70mg/dl) for secondary prevention and confirmed the safety of such reductions. Until very recently, clinical studies suggested that statins failed to address a significant portion of the total cardiovascular disease burden, in as much as their use was associated with a relative risk reduction of only about 30%. This was largely due to the fact that when targeted to the less aggressive LDLC goals of the past statin drugs failed to address the cardiovascular risk associated with the metabolic syndrome. More recent data cited in the AJC review, however, suggest that event rates approach zero for LDLC reductions in primary and secondary prevention populations to levels of 57mg/dl and 30mg/dl, respectively.

All this being said, I do believe statins have beneficial pleiotrophic effects related to anti-inflammatory and other properties. I suspect these effects may be of relatively greater importance in the near term in situations such as acute coronary syndrome. With long term use LDLC reduction assumes greater importance.