Wednesday, November 7, 2007

Plavix Defeated: Prasugrel is superior in a properly designed and executed study

Published early on Sunday, November 5th in the NEJM ( is a randomized controlled superiority trial comparing clopidogrel to a novel agent - Prasugrel.

Prasugrel was superior to Plavix. And it was superior to a degree similar to the degree to which Plavix is superior to aspirin alone. (See

So therefore, by precedent, if one accepts the notion that aspirin alone is inferior to aspirin and Plavix because reductions in death and MI on the order of 2-3% are thought to be non-negligible (as I think they should be considered), one must therefore accept the notion that given the choice between Plavix and Prasugrel, one should choose the latter.

There is this issue of bleeding. But, eschewing your tendency towards omission bias, as I know you are wont to, you will agree that even if bleeding is as bad as death or MI (and it is NOT!), the net benefit of Prasugrel remains positive. Bleeding gums with dental flossing is annoying until you compare your life to your neighbor in cardiac rehab after his MI.

There is also the issue of Plavix's patent expiration in a few years. If the medications were equivalently priced, the choice is a no-brainer. If Prasugrel is costly and Plavix is generic, the calculus increases considerably in complexity - both from the perspective of the patient paying out of pocket, and the policy expert wielding his cost-effectiveness analysis. If my co-pay were the same, I would certainly choose Prasugrel. But if money is/were tight, I might consider that diet and excersise (which are free, financially, at least) may be a more cost-effective personal intervention than the co-pay for an expensive drug.

And what if Plavix at a higher dose is just as effective as Prasugrel? That question will have to be answered by future RCTs, which may be unlikely to happen if Plavix is about to lose patent protection...


  1. I agree that the efficacy is better with prasugrel than with Plavix. Would you not agree that the loading doses were not of equal potency and that the current ACC/AHA, ECC/CPR and UA/NSTEMI guidelines recommend that Plavix be started immediately in the ER and not per the TRITON dosing regimen? Another vascular event can occur immediately after the first event and one would be negligent to wait until the patient goes to the cath lab.

    You do put an interesting spin on the TRITON trial though. Thank you for your insight.

  2. The FDA hopefully will not agree with your conclusions Dr. Aberegg. Until you are a cardiothoracic surgeon or interventional cardiologist and have to deal with bleeding, you cannot comment on this drug.

  3. I wonder if the last poster has any meaningful substantive criticisms of the Prasugrel blog, or if he merely wishes to proscribe my commentary on the basis of my specialization?

  4. Thank you for your blog. I would just like to add a few points. Yes, Prasugrel was proven superior. But, it was only driven from the nonfatal MI's in the study (40% from enzyme changes post PCI). And as we all know, enzyme changes after PCI are inevitable. Take out nonfatal MI and there is no superiority. Another point, contraindication in stroke and TIA patients? How many of my patients have had a TIA that they don't even know of? As the saying goes, "When the pipes are rusty in one vascular bed, then they are rusty in another...". CABG related bleeding; watch out! I am surprised that the FDA even approved this do many of my peers apparently due to the sluggish uptake across the country. And Plavix just had a 600 mg study versus 300 mg with robust results! Prasugrel is a dead beat me too agent.

  5. Properly designed study? Since when is a properly designed study in opposition to updated ACC/AHA guidelines. I practice evidenced based medicine!

  6. I have to agree with the comments made by anonymous regarding what powered the primary endpoint. We must be careful to carefully scrutinize where the results are coming from before making a sound clinical judgement. I too have enzyme changes after PCI and so am not overwhelmed by this study. My CT surgeon colleagues are not thrilled with the CABG bleeding rates. Therefore I will keep using Plavix until it goes generic in 2011; which is not that far off.

  7. These are good comments. I would challenge you, however, to look across your practice patterns to see if they are consistent. If you use Plavix for an ACS on the basis of the CURE study (NEJM, 2001), you are relying on evidence that is no more robust than what exists for Prasugrel, and you likewise assume a similar risk of bleeding.

  8. Thank you for your comments Dr. Aberegg. I am very familiar with the CURE data. You must remember that CURE was Plavix versus PLACEBO (not another therapeutic agent). Both arms of the study included aspirin. I challenge you to review the OASIS 7 study results. Doubling the Plavix dose was associated with great risk reductions and no more major bleeds except CABG related. I am quite impressed with this data myself considering that this is how I currently practice and I now have validation. I do believe that Plavix will eventually be dethroned by a superior agent. I just don't believe that it is Prasugrel.

    Thank you for your blog.