Figure 3. A hypothetical example of the limitations of dose-titration studies and the importance of controlling for treatment exposure when examining the benefits of reaching treatment targets.

*In this hypothetical example, megastatin reduces both cardiovascular (CV) risk and levels of low-density lipoprotein (LDL) cholesterol, but reduction of the latter is not related to megastatin's benefits. The maximum relative risk reduction (RRR) for CV events is achieved with 40 mg of megastatin, and maximum reduction in LDL cholesterol levels is achieved with 80 mg of megastatin. All results can be calculated from the assumptions in section A or can be obtained from the first author by request. The adjusted observational (cohort) analysis controls for dose of megastatin and finds that reaching the LDL cholesterol goal is not an independent predictor of degree of CV risk reduction. To convert LDL cholesterol values to mmol/L, multiply by 0.02586.