Is it too soon to say we were off base on the heart attack cholesterol deal?

Several thoughtful bloggers, on the heels of the Enhance trial, have raised the question and given their views of the issue of "should the cholesterol -coronary artery disease hypothesis be re-visited and perhaps revised." Dr. DB correctly, in my view, suggests that we may have been too literal and dogmatic about the LDL "targets" and Dr. Howard Brody is a bit more sweeping in his foray into revisionism but both make good points.

It is certainty possible that the well proven reduction in CAD incidence may be due at least in part to an effect or effects of the statins apart from their ability to lower the LDL cholesterol. The Enhance trial failed to show that a more marked LDL cholesterol lowering brought about a greater reduction in blood vessel wall thickness and in a study not powered to show it did not show any changes in the attack rate of CAD in its various clinical presentations. So, I would characterize this as a failure to demonstrate that greater lowering of LDL was associated with a beneficial change in a CAD surrogate and really nothing more.

If memory serves lowering the LDL with niacin and by certain types of bariatric surgery have also been associated with lowering of the incidence of coronary artery diseases indicating that the correlation of lowering LDL and decreased heart attacks is not unique to the statins.

Could the maxim that the decrease in CD is proportional to decrement in LDL be a oversimplification? Of course, the magical linearity of CAD and LDL level with the claim that a x change in LDL brings about y change in CAD always did seem a little to pat to really tell the whole story.

But again I have to bring up that Enhance dealt with a surrogate marker whose ultimately relationship to what we probably really care about ( number of heart attacks etc) is not known and we continue to learn how reliance on surrogates can get us in trouble.

Now, both the American College of Cardiology and The American Heart Association have advised us all to just sit there and not do anything which probably makes sense. Even so, the speed with which they presumed to advise us all not only struck me as at least interesting and stimulated Dr. Roy Poses to point out some interesting things about those advisories and the folks responsible for them. In this regard and in numerous others he has done a yeoman's job of educating his readers about the "pervasive web of conflicts" that involve so many physicians many of whom are labeled as thought leaders and various types of medical organizations that many of us have generally relied upon to give good sound, unbiased advice and recommendations.

Steve Lucas, in a comment to DR DB's posting on the Enhance trial, makes a very quotable comment - namely that this is another instance of marketing overtaking science.

And it is not only the medical bloggers that are contemplating what we may really maybe doing with statins for almost everyone, Business Week has a lengthy article on statins as well, raising the question of oversell- replete with NNT numbers.