September 15th, 2014

Selections from Richard Lehman’s Literature Review: September 15th

CardioExchange is pleased to reprint this selection 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 11 September 2014 Vol 371

Prehospital Ticagrelor in ST-Segment Elevation Myocardial Infarction (pg. 1016): Ticagrelor has had mixed fortunes since it was introduced as a new thienopyridine platelet aggregation inhibitor a few years ago. The PLATO trial left lingering doubts whether it is better than the much cheaper clopidogrel when used in acute coronary syndromes. Rather than attempting to resolve these, the latest trial (ATLANTIC) compares prehospital administration of ticagrelor with in-hospital administration in patients undergoing immediate percutaneous coronary intervention for ST-elevation myocardial infarction. There is no difference. The name ticagrelor keeps reminding me of Excelsior, in Henry Wadsworth Longfellow’s poem of that name:

THE SHADES of night were falling fast,
As through an Alpine village passed
A youth, who bore, ‘mid snow and ice,
A banner with the strange device,

but alas, several stanzas later:

A traveller, by the faithful hound,
Half-buried in the snow was found,
Still grasping in his hand of ice
That banner with the strange device,

His name was Herbert Seneca,
He worked for Astra Zeneca,
And ere he died he thought it nice
To use with every stent device

There, in the twilight cold and gray,
Lifeless, but beautiful, he lay,
And from the sky, serene and far,
A voice fell, like a falling star,

Ivabradine in Stable Coronary Artery Disease without Clinical Heart Failure (OL): Ah, there is much poetry in cardiology, although sometimes it can be hard to appreciate. A negative trial of Ivabradine in Stable Coronary Artery Disease without Clinical Heart Failure will not fill the hearts of most doctors with song. Many indeed may never have heard of ivadabrine, let alone used it, although it has been around for nearly 10 years. Its unique virtue is that it acts by reducing the heart rate via specific inhibition of the funny channel. Now funny channel inhibition has to be poetic. Only it’s a shame that it doesn’t seem to do anything.

Fractional Flow Reserve–Guided PCI for Stable Coronary Artery Disease (OL): Since the COURAGE trial showed that most patients with stable coronary artery disease are as well off on medical treatment as with revascularization procedures, interventional cardiologists have fought back with attempts to find subgroups who might still benefit from their expensive ministrations. The diagnostic test that they favour is fractional flow reserve. To a mere outsider like myself that seems puzzling, since what matters is plaque stability, not some one time measure of perfusion, but I must not doubt the importance of FFR since it was the determinant in the FAME-2 trial. And in this trial, “In patients with stable coronary artery disease, FFR-guided PCI, as compared with medical therapy alone, improved the outcome. Patients without ischemia had a favorable outcome with medical therapy alone.” So what was the outcome? It’s not entirely clear from the abstract, where the naughty NEJM proofreaders have let through something called “myocardial infection.” And the full text also has some seemingly conflicting statements. The trial was not blinded and was stopped prematurely due to an excess of revascularization procedures in the medical therapy group. I will leave you to pore over the details of this trial, funded by the stent manufacturer St Jude. As for the poetry, that’s easy: every civilized person should know the lines from Milton’s Lycidas about FAME as the result of honest endeavour:

Fame is the spur that the clear spirit doth raise
(That last infirmity of Noble mind)
To scorn delights, and live laborious dayes.
(English Poems, 1645)

JAMA 10 September 2014 Vol 312

Open Access to Clinical Trials Data (pg. 1002): There is more rather unpoetical cardiology in this week’s JAMA, but first read some masterly prose: Open Access to Clinical Trials Data by Harlan Krumholz and Eric Peterson. Go on, click the link: it’s free and will take you just a couple of minutes to read. It’s a perfectly stated argument for data openness. My only worry is that when data do become freely available, too few people will have the time, resources, and tenacity to dig deep into them.

Effect of Darapladib on Major Coronary Events After an Acute Coronary Syndrome: The SOLID-TIMI 52 Randomized Clinical Trial“ (pg. 1006:) — see what I mean about unpoetical? I defy anyone to find a convincing rhyme for darapladib. Or indeed for lipoprotein associated phospholipase A2, which it inhibits. This is supposed to interfere with plaque formation and inflammation.

So said Glaxo Smith & Kline
While working out their trial design:
Countless billions might accrue.
But given after ACS
Its effect was nil or less.
Alas, alas for darapladib:
Another hopeful drug has had it.

Lancet 13 September 2014 Vol 384

Glucagon-like Peptide-1 Receptor Agonist and Basal Insulin Combination Treatment for the Management of Type 2 Diabetes (OL): In the catastrophizing parlance of the Lancet, type 2 diabetes is sometimes described as a “public health emergency.” If people must use this kind of language, they should really be more careful to distinguish between a challenge, a problem, a disaster, and an emergency. Describing the rise in type 2 diabetes as an emergency suits pharmaceutical companies because they want to sell drugs for diabetes without waiting for substantive proof of long term benefit. I have made this point so often that I will let you off for yawning. But what have we here? A systematic review of glucagon like peptide-1 receptor agonist and basal insulin combination treatment for the management of type 2 diabetes, which reads more like an advertising hoarding than a scientific paper. “GLP-1 agonist and basal insulin combination treatment can enable achievement of the ideal trifecta in diabetic treatment: robust glycaemic control with no increased hypoglycaemia or weight gain. This combination is thus a potential therapeutic strategy that could improve the management of patients with type 2 diabetes.” It’s so wonderful that they’ve even had to make up a new word to describe it. I think “trifecta” means something that has three effects, but there’s one fecta that counts above all in type 2 diabetes: reduction of vascular end points. And I excuse you a second yawn, but I just have to keep saying this as long as papers of this sort find their way into high impact journals.

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