Interventions to Lower Low-Density Lipoprotein Cholesterol and Cardiovascular Risk To the EditorDr Silverman and colleagues1 examined the relationship between lowering low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk reduction amongdifferent statin and nonstatin therapies. We think that further discussion about the statin therapeutic group is needed. In the study,1 the entire statin classwas investigatedwithout distinguishing the different types and doses of statin therapy administered. This approachmight beoverly simplistic. The number of different statins is large, with variation in the active compounds, associated effects, and therapeutic doses. Several reports indicate that there is a gradient in the cardiovascular risk reductionaswell as thesafetyprofile across different types and doses of statins, with lower efficacy associatedwithmoderatedoses asopposed tomore intensivedose therapy.2,3 The inclusionof lowerdosesmightblunt amore robust effect of high-dose statin therapy on cardiovascular outcome reduction. Moreover, this type of meta-analysis does not fully take intoaccount thedifferences in the lengthof the individual trials with respect to cardiovascular benefits. Some of the nonstatin lipid-lowering trials4,5 reportedbenefits onlyafter 7.4years and 9.7 years, whereas most of the statin trials showed benefits at much earlier time points. These findings suggest that thebeneficial effectsof statinsoccurmore rapidlyandmaynot be entirely dependent on cholesterol reduction but on pleiotropic effects, which are different across the various types (lipophilic vs hydrophilic) of statins administered.