The Reply:
      We appreciate Dr. Cohen’s comments, but take issue with some of his conclusions and assertions. First, we disagree that it is “well known that… treatment outcomes in everyday medical practice can vary greatly from those in controlled clinical studies.” In fact, that was the central purpose of our study. We are concerned that clinicians will uncritically adopt the treatment guidelines provided in package inserts, which have been derived from the ideal conditions of a randomized study. The disparity in our own clinical outcomes relative to those projections motivated our analysis.
      Second, we are confused by Dr. Cohen’s statement that the fact that a substantial proportion of our patients (38%) achieved low-density lipoprotein (LDL) cholesterol reductions that were greater than predicted by package insert parameters “explains” those patients “who cannot tolerate standard initial statin doses.” We reported no data on tolerance or intolerance, and our results cannot address whether these patients would have achieved their individual target LDL cholesterol levels at lower doses.
      Third, the studies that Dr. Cohen cites in support of his statement that “dose-related adverse effects, such as myalgia and gastrointestinal discomfort, are major reasons why 50% of patients quit statin treatment within months of starting” used data derived from large administrative databases of elderly subjects with free or low-cost medication. There were no individual clinical data available, and no information, as stated by the authors, on adverse events.
      However, we agree that “statin doses must be gauged to individual response and tolerance”—which is, of course, our practice. Our report was confined, for purposes of generalizability, to patients receiving standard doses of the most commonly used statins, but each drug and dose were selected on the basis of each patient’s risk status and LDL cholesterol level. This is related to our next area of confusion: Dr. Cohen’s assertion that many of our patients “required upward adjustments in their statin dosages, but did not receive them.” Again, the data we reported were primarily for the first follow-up visit, with the goal of examining initial LDL cholesterol reduction. We did report on a fraction of patients at a second follow-up visit that maintained the same dose. Although this reveals that LDL-lowering outcomes for the prescribed dose are similar to that of the initial follow-up visit, the basis for subsequently increasing or decreasing doses (which we certainly hope we did appropriately), or whether patients eventually achieved their LDL cholesterol targets, cannot be evaluated from our report or the data provided. Dr. Cohen does, however, raise an important point. There is considerable data to suggest that physicians do not titrate statin doses upward after the initial prescription, a likely contributor to the “treatment gap” between cholesterol-lowering guidelines and actual practice.