March 16th, 2015
Selections from Richard Lehman’s Literature Review: March 16th
CardioExchange is pleased to reprint this selection from Dr. Richard Lehman’s weekly journal review blog at BMJ.com. Selected summaries are relevant to our audience, but we encourage members to engage with the entire blog.
NEJM 12 March 2015 Vol 372
Endovascular Therapy for Ischemic Stroke with Perfusion-Imaging Selection (pg. 1009): Stroke is a wonderfully straightforward word. When used in a medical context, everybody thinks of a sudden blow. It is something that needs swift action. But actually “stroke” isn’t a straightforward word: ask the cat that has just jumped on to my lap. Now it means a slow and pleasurable process in which she purrs while I pass my hand along her back. That’s the problem with words with deep Indo-European roots: the *streig root is well preserved in several languages, but over thousands of years it has come to mean almost opposite things. And brain strokes can vary between anything from a hammer stroke, which obliterates life, to a brush stroke, which causes some local weakness for a few days. The problem lies between the two ends, and in the need for investigations and treatment to be done at great speed. Two trials of endovascular therapy for ischaemic stroke with perfusion imaging selection in this week’s NEJM present a major advance in stroke treatment, but also illustrate these difficulties. The interventions compared in the first trial (mainly Australian and publicly funded) were intravenous alteplase within 4.5 hours with or without endovascular thrombectomy using the Solitaire FR (Flow Restoration) stent retriever. The patient groups had a mean age of 68 and 70 (the groups were not perfectly matched), and had occlusion of the internal carotid or middle cerebral artery, and evidence of salvageable brain tissue and ischaemic core of less than 70 ml on computed tomographic (CT) perfusion imaging. The trial was stopped prematurely because the thrombectomy group showed markedly better neurological improvement at three days and 90 days.
Randomized Assessment of Rapid Endovascular Treatment of Ischemic Stroke (pg. 1019): The second trial was broadly similar and had a similar outcome: it was stopped early for efficacy. It was funded by Covidien, the manufacturers of the Solitaire FR device, but unlike the publicly funded trial it did not insist on the exclusive use of their product—strange! Anyway, the message is clear. If you have the means to select these patients, by CT angiography and CT perfusion imaging, then they will have a 2.6 fold better chance of a good neurological outcome if treated first with IV alteplase and then with a reperfusion procedure within 60-90 minutes. But pause a minute to consider what this might mean for stroke service provision. Time is of the essence: previous trials of reperfusion, like MR CLEAN, failed because their time frames and selection procedures were looser. So you need very rapid means of transfer and cutting edge CT technology with a team able to interpret it. The team must then discuss their recommendation with the patient or relatives, and proceed at once to perform a quite sophisticated procedure with its own hazards and learning curve. Adoption will not happen at a stroke.
JAMA 10 March 2015 Vol 313
Innovation and Implementation in Cardiovascular Medicine (pg. 1007): “The TAVR [transcatheter aortic valve replacement ] story is a wonderful example of a transformative technology that began with an idea many dismissed, gained momentum through iterative device modifications pioneered by industry, earned an increasing sense of feasibility with animal research and early human studies, achieved US Food and Drug Administration approval after reporting of findings from a pivotal randomized clinical trial, and expanded to additional clinical sites that met quality standards.” In their Viewpoint on Innovation and Implementation in Cardiovascular Medicine, the president of the American College of Cardiology and his colleague cite this “wonderful example” of the American Dream come true, but go on to lament the paucity of other examples. The answer? America needs more young heroes. “Established researchers and institutions need to support and mentor the next generation of innovators. If the courageous pioneers of cardiac surgery did not have the freedom to experiment or the strength to fail 50 or 60 years ago, where would cardiovascular care be today?” I see their point, but cardiovascular care today all too often consists of doing the interventions; plonking in the drugs (regardless of individualised preferences and likelihood of benefit); and a spiral of cost, futility, and repeated admission as the inevitable end approaches. The true heroes, young and old, will be the physicians and researchers who help to meet the difficult and exhausting needs of real people on the way to cardiac death.
Statin Intolerance (pg. 1011): Last year, the statins debate took some strange and personal turns in the UK. The issues were complex and entangled in unhelpful ways, but one fundamental question is that of statin intolerance: why do the findings of clinical trials and clinical experience appear to differ so much? The best way to determine the true prevalence of statin related muscle pains would be through a large series of n-of-one trials with complete blinding and adequate washout periods; but this is never going to be practical. The worst would be to depend on GP record entries and patient discontinuation. There are some in-between possibilities and I look forward to Ben Goldacre’s coming short book on the topic. In the meantime, if you are interested in the issue, look up this quite useful Viewpoint.
Clinical Outcomes at 1 Year Following Transcatheter Aortic Valve Replacement (pg. 1019): So just how wonderful an example of a transformative technology is TAVR (transcatheter aortic valve replacement)? This study looks at 12 182 procedures performed from November 2011 to the end of June 2013 in 299 American hospitals. The sex ratio was equal and the median age was 85. Most of these people would have been expected to die within a year or two, as TAVR is still mostly a last ditch procedure for people too frail to have open replacement. Among the patients who had TAVR, overall mortality was 23.7%, the stroke rate was 4.1% at one year follow-up. So at present we know that TAVR buys time in the very elderly: the other uses mentioned in the Viewpoint still need fuller evaluation. This is not yet the full American Dream.
The BMJ 14 March 2015 Vol 350
The Diagnostic Accuracy of the Natriuretic Peptides in HF: B-type natriuretic peptide (BNP) is the voice of the ventricles. When things are fine, it is heard as a low hum of content, but put the heart under strain and the murmur becomes a growl, and then a shout. All this happens within a few minutes, and dies down within half an hour. If you remember this, you will see why plasma BNP (or NTproBNP) has the diagnostic characteristics that it has. Below a certain level, it rules out “heart failure.” Above a certain level, it indicates that there is a problem, but it doesn’t tell you what it is or how long it has been going on. You can’t tell which ventricle is shouting or why. Used to monitor treatment, BNP fails because there is too much random variability or background noise. This systematic review sets itself the poorly defined task of “assessing the diagnostic accuracy of the natriuretic peptides in heart failure.” This turns out to mean acute heart failure, and sure enough the review concludes that a heart which is not shouting out BNP is not a heart that is failing. Beyond that, don’t trust it. If your patient has chest crackles and a high BNP, that could be heart failure; or it could be a chest infection with a degree of right ventricular overload. I have had quite a long relationship with this peptide, and it’s been a bit of a disappointment.
Drug Disease and Drug-Drug Interactions: “In this review of NICE clinical guidelines, potentially serious drug-drug interactions were relatively common among recommendations for each of three index conditions (type 2 diabetes, heart failure, and depression) and 11 other common conditions.” This is massively important. We are poisoning far too many patients with guideline driven medicine and thoughtless polypharmacy, not helped by computer systems, which cry wolf so often about drug interactions that we have ceased to take any notice.