Tag Archives: Steven Nisse

The most unpronounceable failure yet

Every day a billion things pop into my inbox, and I find my thought dragged this way and that. Mainly, what should I blog on next, and can I be bothered…..so much wine to be drunk.

However, I thought I should give everyone a quick head up on VARESPLADIB. This is the first and last time you are going to hear of this drug, so listen up. The first thing I would like to draw your attention to is the list of authors

Stephen J. Nicholls, MBBS, PhD; John J. P. Kastelein, MD, PhD; Gregory G. Schwartz, MD, PhD; Dianna Bash, RN; Robert S. Rosenson, MD; Matthew A. Cavender,MD, MPH; Danielle M. Brennan, MS; Wolfgang Koenig, MD; J.Wouter Jukema, MD, PhD; Vijay Nambi, MD, PhD; R. Scott Wright, MD; Venu Menon, MD; A. Michael Lincoff, MD; Steven E. Nissen, MD; for the VISTA-16 Investigators 1

Notice anything. Ah yes, Steven Nissen appears once again on a major study. He certainly gets about does our Steven. Another name that means much to me, but nothing to you, is John P Kastelein….he gets about too. Hardly a day passes without these guys running a major clinical trial, and then writing about it. I think they must have been cloned in the past to get through so much work.

Anyhoo,  enough of them. What is, or was, VARESPLADIB, and why should you care. Here from the study itself.

‘Varespladib methyl is a nonspecific pan-sPLA2 inhibitor with favorable effects on atherosclerotic lesions in animal studies. Initial studies demonstrated that varespladib reduced levels of sPLA2-IIA by morethan 90%,in addition to lowering low-density lipoprotein cholesterol (LDL-C) and C-reactive protein (CRP) in patients with stable coronary disease and ACS.’

So now you know. Or maybe not.

Stripped to its basics, varespladib (which I shall PLAD) is an anti-inflammatory drug specifically designed to reduce the inflammatory cascade that is thought to be a major cause/risk factor for heart disease. Not only that, but it reduces LDL ‘bad/naughty cholesterol’ and C reactive protein too – a sign of inflammation in the arteries. Possibly CRP may even be a cause of CHD… in truth you might think it is a cause, if you are idiot.

Some years ago I wrote that we should await the C-reactive protein lowering agents. On the basis that a high CRP levels had been identified as ‘risk factor’ for heart disease. I wasn’t sure if it would happen, but I suspected it would. I predicted that lowering CRP would be a complete and utter waste of time.

Inflammation cannot, I have always said, be the cause of anything. Inflammation is the way that the body heals itself. If you cut yourself you will develop a red and inflamed area around the cut, otherwise known as inflammation. The inflammation did not cause the cut, the cut caused the inflammation.

However, such is the idiotic thinking in heart disease research that various people, led by Paul Ridker, decreed that inflammation causes heart disease (and not the other way around). They then decreed that if you could lower the inflammation that the risk of heart disease would fall. The noise in the background is the mad stampede of pharmaceutical companies rushing off to find drugs to block the inflammatory pathway, lower CRP, and cure heart disease.

Enter PLAD. Here we have a drug that lowers inflammation, lowers CRP, and as an extra added bonus  lowers LDL ‘bad/naughty’ cholesterol, so it should provide a triple benefit. And guess what we find:

‘At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm.’

The conclusions:

‘In patients with recent ACS (acute coronary syndrome – a heart attack to you and me), varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS.’

I am sure that there are a whole new bunch of anti-inflammatory agents out there, being trialled as I write this. I am also sure that they will fail. Hey guys, you could save billions if you read my stuff.

Now, repeat after me. Blocking inflammation blocks healing. Block healing and you die. End of. Time for a glass of wine.

1: Varespladib and Cardiovascular Events in Patients With an Acute Coronary Syndrome The VISTA-16 Randomized Clinical Trial. JAMA. doi:10.1001/jama.2013.282836