Saturday, 13 October 2012

Do you want a reprint with that? My 'bad pharma Friday'.

"Yes", I said, vaguely remembering the debate on aldosterone antagonists from a couple of years ago but not being able to recall exactly what it was all about.

We had a presentation in the hospital from a Pfizer rep on their drug eplerenone (Inspra) and it went through the results of the EMPHASIS-HF trial [1] talking about how that  has affected the European Society of Cardiology guidelines for heart failure and how the local cardiologists apparently 'use it anyway'.

A reprint of the EMPHASIS-HF trial was offered and I then saw that, yes, it was a Pfizer-sponsored trial of eplerenone against placebo. Also, it did not include the accompanying editorial in the same issue of the NEJM by Paul Amstrong.

There are two issues here:
  • Selective reporting of evidence. It was not made clear that the major change to the guidelines was in the placement of mineralocorticoid antagonists (spironolactone AND eplerenone) ahead of ARBs which state: "ARBs are no longer the first choice recommendation in patients with HF and an EF ≤40% who remain symptomatic despite optimal treatment with an ACE inhibitor and beta-blocker. This is because in EMPHASIS-HF, eplerenone led to a larger reduction in morbidity–mortality than seen in the ARB ‘add-on’ trials discussed below, and because in both the Randomized Aldactone Evaluation Study (RALES) and EMPHASIS-HF, MRA treatment reduced all-cause mortality, whereas ARB 'add-on' treatment did not.". The RALES trial showed the benefits of spironolactone in a similar group of patients [2].
  • Selective reporting of opinion. The editorial commentary which suggested that the more expensive eplerenone should be reserved for those who do not tolerate spironolactone was not addressed. Notice also how the Pfizer-sponsored trial is freely available on NEJM but the accompanying editorial is not. Shame on you NEJM. Freely available copies of the editorial are available here, and here. Other commentators agree. As our National Prescribing Centre (NICE) points out "the results are consistent with those seen with spironolactone in the RALES study".
Now I'm no cardiologist and I haven't ever prescribed eplerenone but, to me, my 'bad pharma Friday' looked like a bit of a demonstration of nice outcomes data of a slightly better tolerated but patented expensive drug versus placebo whilst hiding the real debate about its position in the treatment algorithms compared with another effective, off-patent, much cheaper drug.

Time to read my Kindle copy of Ben Goldacre's new book 'Bad Pharma' I think.

1. Zannad F, McMurray JJV, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, Vincent J, Pocock SJ, Pitt B. Eplerenone in patients with systolic heart failure and mild symptoms. N. Engl. J. Med. 2011 Jan;364(1):11–21.

2. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N. Engl. J. Med. 1999 Sep;341(10):709–717.

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