Roxana Mehran， M.D.
Course Director， Clinical Research Workshop
New York-Presbyterian Hospital/Columbia University Medical Center
Joint Chief Scientific Officer， Cardiovascular Research Foundation
<International Circulation>:When you look at a clinical trial， what are some the key factors that you use to evaluate the merit of a particular trial?
Roxana Mehran: I think it is really important and essential that when you are looking at the results of a clinical trial to see how it was designed， the hypotheses that were generated， the assumptions that were made， and the statistical analysis plan as well as the conduct of the trial itself. We need to look at whether it was multi-centered， randomized， monitored， and conducted through multiple entities， so that it really passes the muster of a well-conducted study. I think those points are extremely essential. One needs to really look specifically at the design of the trial and assumptions that were made for the trial， because trials are often designed to answer the questions that the sponsor wants answered in their favor. In addition， one really needs to take a step back and look at the trial in its highest scientific vigor.
<International Circulation>:In the session this morning about pre-clinical studies you were discussing whether animal studies translate into human results. What has been your personal experience in this area? Do results of animal studies generally translate into humans?
Roxana Mehran: It is more often that animal studies do translate into what happens clinically， otherwise they wouldn’t be done. It is our only tool to assess the safety profile of something before it is placed into human beings. Of course， you must know that there are always limitations， and nothing is a perfect science. There are obviously good examples of when animal studies did not translate; they look good in the animal but they look terrible in the human being. However， I think for the most part， if you see a signal in the animal， one needs to be certainly worried about that particular signal and look for it in the clinical trials. That does not mean if you see a signal that you can not put that device in a human being， but you have to be careful about it. Think about what Cypher and Taxus stents have done in protecting so many patients against restenosis. There certainly was a signal， but had we not been given the opportunity to do human studies， we would not have had opportunity to have drug-eluting stents in our arena. Obviously the signals did mean something， especially with late stent thrombosis， and that was something we were able to address.
<International Circulation>:Currently there are some new adjunctive drugs such as prasugrel that support PCI for patients with STEMI， according to the updated ACC/AHA 2009 guidelines. What is your opinion about prasugrel and what are the advantages or disadvantages of this drug?
Roxana Mehran: I actually have a lot of experience with that particular study and the results. Obviously， the sub-study in the STEMI population looks fantastic from the TRITON-TIMI 38 study but there needs to be full knowledge of the fact that particular drug was never studied in STEMI patients a priori. It was a pre-specified sub-analysis so you have to look at it; you can’t ignore it. However， I think we need to have long term and well powered studies to learn the safety and efficacy of prasugrel in the STEMI patient population. What concerns me about the STEMI patients is that we are so fast in treating them， if you give them a dose of prasugrel without knowing their history of bleeding diathesis， etcetera， that we may get into trouble in just applying it to all STEMI patients. There has to be a gatekeeper that takes care of the important risks that prasugrel has in the patients who are prone to bleeding. And that does need to be eliminated. Because if you do that to all STEMI patients across the board， then we are going to have a lot of patients dying of inter-cranial bleeds and I think that is important to make that distinction up front in the patients with STEMI.
<International Circulation>: Bivalirudin has been included as a class-one recommendation as an anticoagulant therapy for primary PCI. Do you have a view on this change?
Roxana Mehran:Of course I do， because I conducted the HORIZONS AMI study and I think that was the one trial where we showed that by having a drug that was associated with less bleeding we actually saved lives and we did not have to pay any tax on ischemic complications， so I think that is a fantastic choice. The one piece we have to work out is the stent thrombosis. Prasugrel seems to be the right fit， but it needs to be studied in order to say that it should be applied， across the board， to all STEMI patients.
[下一页] [1] [2] [3] [4]