May 21st, 2012

Selections from Richard Lehman’s Literature Review: Week of May 21st

CardioExchange is pleased to reprint selections from Dr. Richard Lehman’s weekly journal review blog at Selected summaries are relevant to our audience, but we encourage members to engage with the entire blog.

NEJM  17 May 2012  Vol 366

Warfarin vs. Aspirin for Stroke Prevention in HF (pg. 1859): Here’s a big international study to settle the question of whether warfarin or aspirin is better at preventing stroke and mortality in heart failure with sinus rhythm. Well, that’s what the title would have you believe. In fact this is a truly old-fashioned study which defines “heart failure” by an ejection fraction under 35 and so ends up with a cohort of patients of mean age 61 and 80% male. It tells you nothing at all about your average patients with clinical heart failure who have a mean age of 76 and are 50+% female, half with normal ejection fractions. Their chances of going into atrial fibrillation and throwing off clots are much higher than those of this cohort. Someone needs to do a trial comparing a fixed-dose new generation anticoagulant with aspirin in this “real world” population.

CVD Risks of Azithro (pg. 1881): This study about the increased risk of cardiovascular death while taking azithromycin has got a lot of publicity. The increase in CV death for the average adult population is put 47 per million taking a five day course of this antibiotic rather than amoxicillin: it is considerably higher in those at increased CV risk, of course. But there is an easy way to remember not to give this or any other macrolide antibiotic to those at highest risk: just heed your computer warning that all these drugs interact with statins.

Another cup of Joe (pg. 1891): The paper that got the most publicity in this week’s New England Journal though was this one showing that coffee consumption is associated with lower all-cause mortality. This seems dose-related too, which is good news as I sit here all a-buzz from a mug brewed to the strength my wife likes. Legend has it that coffee reached the West via the Turkish armies who were defeated at the walls of Vienna in 1683, complete with bread rolls in the shape of the Islamic crescent. Which is still the best – and now perhaps the healthiest – breakfast; and the surest mark of advanced civilization.

Lancet  19 May 2012  Vol 379

After flirting briefly with items in the On-line First sections of the journals, I’ve largely gone back to the weekly printed items, for the sake of simplicity. But two papers on The Lancet’s website this week cry out for comment, as they put the final nails in the “treat-to-target” lipid management coffin. I hope.

Statins Work: The first one is old news, but repackaged as a huge meta-analysis of individual patient data from 27 randomized trials of statins which included subjects at low risk of cardiovascular events. Guess what? Everybody’s risk came down, whatever it was to start with. And the mortality benefit of the statin therapy was directly in proportion to the fall in LDL-cholesterol, and it far outweighed any measurable harms. So should everybody take a statin, so as to reduce the population rate of CV disease? No, I object to this kind of public-health-speak: everyone who wants to should be able to: it’s a personal choice. And does this prove that statins work by LDL-C lowering? Again no. They just work, and people should take them or not, as they wish to adjust their life chances.

We Don’t Know How HDL-C Works: And now onto the question of “good” cholesterol – HDL-C. There is a linear relationship between this lipid fraction and a decrease in cardiovascular risk. So far, 200 or more trials have been done with HDL-C raising agents; and not one of them has succeeded. Roche has just terminated its trial of dalcetrapib for futility, leaving the Oxford CTSU trial of anacetrapib (REVEAL) about the only one left standing. I wonder if it will ever recruit its 30,000 subjects. Here a massive Mendelian randomization study shows that the HDL-C/CV protection association is unlikely to be causal, and plasma measurements of HDL-C may actually tell us very little.

BMJ  19 May 2012  Vol 344

AAA: A study from the Highlands and islands of Scotland looks at mortality in men screened for abdominal aortic aneurysm. I was somewhat fazed to see this defined by an aortic diameter of 30mm or more: in the MASS study and in my clinical practice, the threshold was 55mm. But this is only a fairly crude associational study which unsurprisingly shows that the diameter of the aorta in old men is a marker for high cardiovascular risk and cancer risk, almost all of it attributable to smoking.

Arch Intern Med  16 May 2012

Omega-3s (pg. 686): I am an avid eater of all kinds of fish, and I think my absolute favourite is a large fresh herring fried in butter. Unfortunately you probably have to live on the West Coast of Scotland to obtain such an article: away from fishing ports you are safest with kippers, as there is nothing worse than a stale herring. Eating is meant for sustenance and pleasure. It has also been found that eating a diet rich in fatty fish is associated with better cardiovascular health – and if there is any evidence against butter, I have yet to read it. Unfortunately a large proportion of mankind seems to be averse to eating the oilier species of fish, and instead, many seek to obtain CV benefits from omega-3 fatty acid supplements. But as this systematic review reveals, there is no evidence worth the name that these achieve anything for secondary prevention following cardiovascular events.

Fenofibrate (pg. 724): Finally, an insight into the bizarre world of American lipid prescribing: target-driven, irrational, and profoundly distorted by big pharma. Fenofibrate is a drug which has repeatedly been found to have no beneficial effects whatsoever, though it lowers “bad” lipids, including triglycerides. As evidence for its uselessness mounted, fenofibrate prescribing in the USA soared, driven by advertising from Abbott Laboratories. But this $1bn-a-year triumph of marketing over evidence was due to come to an end when Abbott’s patent expired. This paper describes how Abbott fought off the threat of generic competition and continues to sell modified fenofibrate products with rights to exclusivity. Its lead author is Nick Downing, a medical student with a unique accent forged in London and Harvard, whom I met when he first began work on this at the end of his first year as a medical student at Yale last year. Well done Nick! But hang on – what is this I see on the NEJM website? A full special report on regulatory agencies in the US, Europe and Canada, with first author Nicholas Downing. For a second- year medical student to publish one paper in a leading medical journal might be called good fortune; to publish two begins to look like brilliance.

And do read this inspiring advice to Be Brave, from Nick’s mentor Harlan Krumholz.

One Response to “Selections from Richard Lehman’s Literature Review: Week of May 21st”

  1. Jean-Pierre Usdin, MD says:

    What else?

    Thank you dr Lehmann for your always attractive remarks with a humoristic tone which takes the reader stuck until the end of your blog.
    Here are some remarks (unfortunately I am French, my English language is sometime difficult and the French sense of humour does not equal the US one: remember Pdt Obama’s French Fries!)

    1/Coffee works: I am waiting for another meta-analysis indicating that confounders were not ideally treated in this study. I remember few months about black CHOCOLATE. But the coffee goes on and thank you dr Doug/ Clooney.

    2/Omega 3 does not work and so Fibrates but they sell (very) well, changing minimally the dosage permits the carry on. Same things exist in Europ putting two products in the same pill, changing the dosage… and the market goes on.

    3/ Aspirin cheap and universal! Secondary prevention of thrombo-phlebitis (recently published in NEJM) cancer prophylaxis, inflammatory diseases mainly, of course, cardio vascular diseases etc.
    Many lessons arising from this old/new, unpatented drug: and the Aspirin (or aspirin?) goes on!

    Dr Lehmann, with the pleasure to read your future blogs next weeks…
    Paris May 28 th 2012.