July 28th, 2014

Selections from Richard Lehman’s Literature Review: July 28th

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.

JAMA Intern Med July 2014

Comparative Outcomes of Catheter-Directed Thrombolysis Plus Anticoagulation vs Anticoagulation Alone to Treat Lower-Extremity Proximal DVT: When I qualified in the 1970s, all the talk was about how the great days of medical progress had come to an end, that medicine was becoming unaffordable, that we needed to base practice on better evidence, that antibiotics would soon be useless, that doctors didn’t have enough personal contact with patients, that there was not enough emphasis on prevention, that hospitals were becoming outmoded and care should be transferred to the community, that we should look at the wider determinants of health, that America provided the worst model of healthcare in the world, that we should borrow more ideas from America, that the NHS was the ultimate moral standard of health provision/an outdated collectivist idea. Et cetera: dear children, there is nothing new under the sun. We spend our working lives fighting for what good there is until we tire and die. The immediate trigger for these thoughts is a paper about Comparative Outcomes of Catheter-Directed Thrombolysis (CDT) Plus Anticoagulation vs Anticoagulation Alone to Treat Lower-Extremity Proximal Deep Vein Thrombosis. I hope this is self explanatory because I don’t intend to explain it. Looking at over 90 000 hospital admissions for DVT, the investigators find that the percentage treated with catheter delivered thrombolysis doubled from 2.3% in 2005 to 5.9% in 2010. There was no difference in mortality compared with simple anticoagulation, but longer hospital stays, increased costs, and increased adverse events. And 35% of the CDT patients also received vena cava filter placement, a procedure for which there is no evidence either. The authors call for a randomised trial. But how on earth do these procedures still get adopted without any RCT evidence to start with?

The BMJ 26 July 2014 Vol 349

The Epidemic of Pre-Diabetes: the Medicine and the Politics: Last week I was pressed for time and omitted to comment on John Yudkin and Victor Montori’s splendid demolition of “pre-diabetes.” When the full story is known, the dissemination of this bogus concept will be seen as a classic illustration of how the machinations of a lobby of vested interests can triumph over complete lack of evidence. “We need a shift in perspective. It is critically important to slow the epidemic of obesity and diabetes. Rather than turning healthy people into patients with pre-diabetes, we should use available resources to change the food, education, health, and economic policies that have driven this epidemic.” I am optimistic that—thanks in substantial part to the efforts of these two authors—we have reached a tipping point.

Dabigatran and Bleeding: This week’s exceptional issue of The BMJ is dominated by dabigatran and lipids. The blockbuster articles on dabigatran by Deborah Cohen, and Thomas J Moore and colleagues, are essential reading for industry followers, but the Editorial by Blake Carlton and Rita Redberg is the thing to read for everybody. The Food and Drug Administration thought the world needed new oral anticoagulants so desperately that it approved Boehringer Ingelheim’s Pradaxa on the basis of a single trial called RE-LY. “Dabigatran achieved blockbuster status, with sales of over $1bn (£580m; €740m) globally by April 2012 and $2bn in the US by 2014 despite increasing concerns about safety. By December 2011 adverse drug event databases in Europe, Japan, and the US showed thousands of serious and fatal haemorrhages in patients taking dabigatran, particularly older patients.” The selling point of Pradaxa was, of course, that you don’t need to do any blood monitoring, but in the unpublished parts of the RE-LY trial there was plenty of evidence that plasma level monitoring would improve dosing and help to avoid serious haemorrhage. “Society must consider the trade-offs of accelerated drug approval in terms of assurance of safety and effectiveness. A more transparent process of data collection and review would make important clinical data available without waiting for litigation and subpoenas, which is what it took to unearth some of Boehringer’s early concerns with dabigatran.” How many times do we have to say this?

Mass Treatment with Statins: For a variety of reasons, I spent weeks poring over the new NICE guidance on statins, summarized in The BMJ. It really came close to driving me mad, but nature came to the rescue by laying me low with a horrible complex migraine that lasted three days. Since then I have vowed to have no more to do with this document. To me, it’s the NICEst possible illustration of everything that is futile and outdated about guidelines. It barks endless orders (99 with subdivisions, and then some), which if taken seriously would leave no time for the rest of primary care, while providing nothing substantive to guide a genuine open dialogue with the individuals who are expected to take lifelong treatment. It covers its back by recommending dietary modification and activity before drugs, and exonerates itself by saying clinicians are free to do what they like after discussion with patients, but it provides nothing to aid such discussion except an endless list of study analyses. Which in turn brings us to the entirely inadequate state of the evidence for sharing decisions honestly with patients. I’m truly grateful to Ben Goldacre for summarizing this issue so brilliantly: “Mass prescription for modest individual benefit is new. Truly informed choice will require more than good intentions. We will need better data, from bigger trials, and better risk communication than for conventional medical treatment. Delivering this will require us to embed the gathering, communication, and implementation of evidence as seamlessly and cheaply as possible into the everyday routine of medicine. Without such innovation in the use of medical data, we can say only that statins are—broadly speaking—likely to do more good than harm. That is not good enough.”
(P.S. But mass prescription for modest individual benefit is not new. So-called “hypertension” needs to be the next field of battle.)

Non-cardiovascular Effects Associated with Statins: A few months ago, The BMJ came under attack from the high priests of the lipocentric religion for publishing a paper by Abramson and colleagues about the potential harmful effects of statins. Now The BMJ responds by publishing a far more detailed and scholarly traversal of the area by three authors from Johns Hopkins. The next step must be a massive prospective surveillance study—a useful job, perhaps, for the well-funded Clinical Trials Support Unit of Oxford.

Effect on CV Risk of High-Density Lipoprotein Targeted Drug Treatments Niacin, Fibrates, and CETP Inhibitors: Many years ago in these reviews, I called for a halt to trials of HDL-C raising drugs when I did a rough tally based on PubMed and found 200, without one of them showing substantive benefit. This meta-analysis finds 39 trials, which fulfilled stricter criteria, and comes to the same conclusion. Moreover it calls into question the whole lipocentric theory of statin action: “Notably, fine grained temporal analysis shows reduction in events from use of statins long before the plausible time at which lower lipid levels could mediate slower accumulation of atheroma and thereby could have had an effect. Whether the decrease in low density lipoprotein cholesterol level is the principal mechanism for the reduction of acute events by statins is, therefore, unknown.” This simple fact needs constant restating.

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