April 7th, 2014
Selections from Richard Lehman’s Literature Review: April 7th
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 3 Apr 2014 Vol 370
A Controlled Trial of Renal Denervation for Resistant Hypertension (OL): From now on, teaching the crucial importance of proper design in randomized trials will be SYMPLICITY itself. I’ve already taken you through the essentials of this story, after being taken in myself, and there is a superb BMJ editorial as well. Here is the full report of the SYMPLICITY-3 trial which shows that after spectacular results in open label trials, renal denervation does not produce a significant drop in blood pressure which is persistently high after combined treatment with at least three drugs. Correction: it produces a very significant drop averaging 13mm Hg, whereas the sham control procedure produces a drop of nearly 12mm. Let’s just stop and think about that. If you lie a patient down and put a tube in an artery and pretend to fiddle about for half an hour, you can produce a long term reduction of their blood pressure nearly as great as if you actually ablate their renal nerve supply. Explanations on a post card please.
TAVR with a Self-Expanding Prosthesis (OL): Whereas by funding SYMPLICITY-3, Medtronic lost themselves a potential market running into tens of billions of dollars, with this one they may have gained themselves a small niche market in people with aortic stenosis who are borderline for open valve surgery. Patients like this can benefit from transcatheter aortic-valve replacement (TAVR) with a balloon-expandable device, but Medtronic claim superior results from an alternative transcatheter bioprosthesis comprising a self-expanding nitinol frame and trileaflet porcine pericardial valve (CoreValve, Medtronic). Doing device trials is quite tricky, because you need operators to climb a steep learning curve, and here the first three patients enrolled in the trial at each study site were considered to be “roll-in” participants. They did not count in the figures but were there to familiarize the operators with the procedure. The bottom line as stated in the abstract is that “In patients with severe aortic stenosis who are at increased surgical risk, TAVR with a self-expanding transcatheter aortic-valve bioprosthesis was associated with a significantly higher rate of survival at one year than surgical aortic-valve replacement.” But a lot must depend on patient selection; and how many “roll-ins” you’ve practised on.
Survival with CRT in Mild Heart Failure (OL): If I get heart failure with left bundle branch block, I would like to have biventricular pacing (or cardiac resynchronization therapy, CRT). I would want nothing to do with implantable defibrillators. Sudden death—especially beyond the age of 70—seems to me greatly preferable to a decline into weakness, breathlessness, dependency, and repeated episodes of near-drowning. However, in the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT), CRT alone was not on offer. You had to have the defibrillator, with or without CRT. Follow-up at a seven years confirms that CRT reduces all-cause mortality in people with mild systolic heart failure with LBBB from 29% to 18%, with a possibly harmful effect on those without LBBB. There is nothing here about symptom relief, which counts for more than survival to most people with HF.
Lancet 5 Apr 2014 Vol 383
Effect of High-Dose Simvastatin on Brain Atrophy and Disability in Secondary Progressive MS (OL): Statins, as I keep saying, are wonderful drugs. They should be offered to everybody and people should make up their own minds whether to take them, based on the evidence and their personal preferences. What I personally would not do, however, is take simvastatin at a dose of 80mg, because this maximizes the risk of adverse effects while producing a very small marginal benefit compared to a lower dose. But 80mg was the dose given to 70 patients with secondary progressive multiple sclerosis in a phase 2 placebo-controlled trial. The mean annualised rate of brain atrophy was significantly lower in patients in the simvastatin group (0•288% per year [SD 0•521]) than in those in the placebo group (0•584% per year [0•498]). How this 43% reduction in brain shrinkage converts into clinical benefit is uncertain from this relatively small and short RCT, but it certainly suggests that bigger trials with other statins are well warranted in a dreadful condition which is currently untreatable.