May 8th, 2012

Selections from Richard Lehman’s Literature Review: Week of May 7th

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.

JAMA  2 May 2012  Vol 307

Abciximab vs. Manual Aspiration Thrombectomy in STEMI (pg. 1817): For mere bystanders, the world of interventional cardiology never ceases to amaze with its profusion of trials seeking to compare one odd-sounding intervention with another. The bottom line of this paper about the INFUSE-AMI is that intracoronary abciximab is superior to manual aspiration thrombectomy in patients with large anterior myocardial infarction. I guess you have to be either an interventional cardiologist or a trial methodology dweeb to find this very interesting. Bear with me: I am becoming somewhat of the latter, and to me this looks like a complex marketing trial, and intrigues me like a rare fungus (you can skip to the next section at this point). “Atrium Medical was involved in the design and conduct of the study and site selection and had the right to a nonbinding review of the manuscript.” Atrium Medical make coronary artery catheters for drug delivery, so they have a natural interest in promoting the use of intracoronary drug delivery. And one way to do that is to compare it with a technique that has already been shown to fail in the majority of trials – coronary clot aspiration. The thing not to do is compare it with intravenous abciximab delivery, because that might prove just as good. It pains me to list all the other potential defects of this trial, but basically it had a 2×2 factorial design, was single blinded, enrolled only 7.2% of MI patients presenting at 37 sites in 6 countries, used an end-point (infarct size at 30 days) which was not accurately determined in a significant proportion of patients, with a difference in pooled groups of small statistical significance, plus four other disadvantages you can read about from the authors themselves in the Comment section. And by the standards of the trials which regularly appear in the top journals, it is not even particularly bad.

The State of the Union’s Clinical Trials (pg. 1838):  When I was a GP in the prime of life, Muir Gray bade me read a book called Clinical Epidemiology written by a number of Canadians. Reading Sackett et al by day and by night, I suddenly became aware of the wonders of randomized controlled trials, the potential of the internet, the intellectual challenge of using diagnostic tests according to Bayesian principles, the need to seek evidence, evidence, evidence. My heart still aches for the simple optimism of that vision. Instead, most of what we deal with in medicine is complexity made worse by inadequate knowledge. Surely the way forward must lie with further clinical trials. These days, if you want the results of your trial to appear in a peer-reviewed journal, it has to be registered; and the US registry is known usefully as Here the past and present custodians of this site look at the quality of the trials registered between 2007 and 2010. They “are dominated by small trials and contain significant heterogeneity in methodological approaches, including reported use of randomization, blinding, and data monitoring committees.” In other words, these trials are never going to yield clinically dependable data; most of them are futile, and therefore by definition unethical. Something is terribly wrong with the system which governs clinical trials: it is failing to protect patients and failing to generate useful knowledge. Most of what it produces is not evidence, but rubbish. And with no system in place to compel full disclosure of the data, it is often impossible to tell one from the other.

NEJM  3 May 2012  Vol 366

Two-Year Data on PARTNER (pg. 1686): The Placement of Aortic Transcatheter Valves (PARTNER) trial did what it says on the can: placed a lot of new aortic valves via a catheter (TAVR), so sparing patients the ordeal of open surgery. One part of the trial randomized patients at high risk of decompensation to one or other procedure, and at one year the two procedures yielded very similar results for mortality, symptoms and haemodynamic measures. This report gives the two-year results: there is now a divergence towards paravalvular regurgitation in the TAVR group which is associated with higher mortality.

TAVR in Inoperable Decompensating Stenosis (pg. 1696): Another part of the PARTNER investigation randomized patients with inoperable decompensating aortic stenosis to either TAVR or standard management (which often included balloon valvuloplasty). In these unfit elderly patients (mean age 83) with severe heart failure (mostly NYHA III-IV) survival for 2 years was 56.7% in the TAVR group and 32% in the others. So worth a go in “appropriately selected patients”, as the usual phrase has it. The fittest survive the best, even at this level.

Lancet  5 May 2012  Vol 379

Clopidogrel Genetic Testing (pg. 1705):Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): a prospective, randomised, proof-of-concept trial”. Spartan Biosciences have developed a bedside test which allows rapid genotyping for the CYP2C19*2 allele. The simple story is that patients with this allele don’t respond to clopidogrel but do better with prasugrel, and that you can test this by measuring platelet reactivity, which was the outcome measure for this trial. But the evidence from randomized trials of clopidogrel v prasugrel is a good deal less clear. Moreover, I can’t see why a bedside test is needed for patients who have just had percutaneous coronary intervention and are lying in a hospital bed close to a proper pathology laboratory. So the concept that this trial proves is that you can get a Lancet paper out of a genetic test that predicts a surrogate marker, immediately and expensively. What it does not prove, thankfully, is the concept that the future of medicine lies in double rip-off – ripping off for the genetic test and then ripping off for the expensive drug.

Ann Intern Med  1 May 2012  Vol 156

Reducing MI Mortality (pg. 618): Here’s a study of Hospital Strategies for Reducing Risk-Standardized Mortality Rates in Acute Myocardial Infarction: an impeccable paper about an important topic, and moreover one which marries the insights of qualitative research with rigorous quantitative analysis of observational data. Am I praising this too much? I don’t think so, though I have to confess that I’ve been working for the best part of a year among the team that produced it. I thought they were incomparable before, and now I know it for a certainty. So call me biased, but do read this paper: it shows that virtuous care is rewarded, but sadly not by very much. Standardized MI mortality in the 537 US hospitals examined varies by about 10% in a near-normal distribution, but only just over 1% can be accounted for by the factors which emerged from qualitative interviewing of hospital staff: a culture that encouraged physicians to solve problems creatively, physicians and nurses acting as quality-of-care champions, hospital and emergency department clinicians meeting at least monthly to review care, cardiologists always being present in the hospital, and not cross-training nurses to work in both intensive care and cardiac catheterization settings.

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