Thursday, May 03, 2007

Still more good things from statins?

I had wondered before about whether there was anything that statins did not help.The latest breaking observational study suggest that the risk of sepsis in dialysis patients is markedly lowered by statins.

It obligatory to mention whenever an observational study is cited or discussed to say since this was not a randomized trial we cannot infer causality and this should be considered an"hypothesis generating study".

Even so,it is another block in the argument building to emphasize the non-LDL lowering effect of statins,aka "pleotrophic effect".

The makers of the several statin drugs hope to build on the pleotrophic effect foundation to counter the appeal of Zetia which when teamed with a statin ( Vytorin is Zetia plus Zocor) brings about an impressive decrease in LDL cholesterol. The lower-is -better mantra on the part of the National Cholesterol Panel and its ever decreasing LDL target is just what one would want to encourage sales of Zetia and Vytorin. One counterargument from the statin camp is that " yes Zetia plus statin really lowers the LDL but the statin does more than lower the LDL.It has pleotrophic effects" i.e it decreases inflammation or tendency to clot,pacifies platelets or something beside lowering the LDL to decrease the likelihood of an acute coronary syndrome.

Of course, statins have effects other than LDL lowering. How many drugs do just one thing? Even though we emphasize one aspect and even classify a drug on the basis of that one action, e.g. beta-blockers,calcium channel blockers etc,these drugs all have effects other that the one for which they were named.

Crestor ran into a bit of bad sailing what with Vytorin blazing onto the scene and then Sidney Wolfe ( of Public Citizen ) requesting that the FDA remove Crestor from the market arguing that Crestor had a greater risk of myopathy and possibly renal disease. Here is the FDA letter replying to his request and denying it.

If recent thought- leader dinner talks are any indication Crestor is fighting back arguing the shrinkage of plaque that occured with the ASTEROID trial with Crestor -an effect I believe that has not been seen with the rival statins and promoting the idea that the best indicator of risk and of decreasing risk is the level and then the improvement in the LDL/HDL level, a parameter in which Crestor seems to do rather well.

It may well be that the "best" number to treat to is one that uses the LDL/HDL ratio but so far ( at least with ATP 111) the cholesterol mavens encourage docs to use LDL targets and their desire to go with the ATP playbook is one of the reasons that Vytorin is doing so well and Crestor is on the evening dinner circuit to persuade/convince docs that we need to dance with those that brought us, ie the statins which have shown mortality benefit and that as yet has not been demonstrated with Zetia. Stay tuned, I believe a long term study of the effect of Zetia on coronary event rate is being done.

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