The June 6,2008 NEJM published a very important editorial. This is one should be handed out to medical students and house officers. This insightful filled essay was authored by Drs. Harlan Krumholtz and Thomas Lee.Dr. Krumholz is prominent in the area of outcome research and hopefully his views will have a positive impact in reassessing and reining in the current risk factor modification craze which has neglected the fact that how one modifies the factor may change the disease outcome of interest. It might be added that in some instances we have little or no evidence that modifying a risk factor will matter at all as appealing as the pathophysiologic rational may appear.
From the essay we read:
It is increasingly apparent that the specific strategies used to modify them [the risk factors] make a critical difference in patient outcomes.
The now canceled ILLUMINATE trial illustrates dramatically the main point. Raising the HDL with a particular medication (torcetrapib) was associated with a higher mortality rate. How you raise the HDL may well matter.
What do the authors propose?
..we should no longer support the use of target without reference to the strategies used to achieve them....Second, guidelines and performance measures should incorporate more sophisticated and explicit considerations of the risk of the disease and the adverse consequences posed by the intervention.
A clinical trial is ultimately a test of strategy,and we should not be surprised that different strategies may have different effects on patients beyond their effect of risk-factor levels.
You would hope that publishing those thoughts in a high impact journal such as NEJM would have actually have an impact.