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After the surprising, top-line result from the SYMPLICITY HTN-3 trial came out in a press release from Medtronic last January, the question remained of what went wrong: Why did renal denervation fail to outperform a sham procedure in reducing blood pressure?
The apparent answer emerged in late March when the full results finally went public in a report at the annual meeting of the American College of Cardiology and in an article in the New England Journal of Medicine. Many of the 364 patients who underwent active denervation – which involves zapping the efferent nerves that run along the outer wall of the renal arteries with a few brief pulses of radiofrequency energy – probably failed to receive adequate treatment, so their renal innervation remained mostly intact. There’s no proof that’s what happened, but it seems plausible given that all the U.S. operators in the trial had no prior experience performing the procedure, as well as the observation several years ago that denervation can produce highly variable results and is very operator dependent.
Zeina AR, Vladimir W, Barmeir E/Wikimedia Commons/CC-BY-2.0
Renal denervation shows promise, but the results from the SYMPLICITY HTN 3 trial suggest that the procedure may isn’t quite ready for widespread use.
This variability in success had been documented back in the 2000s by one of the pioneers of renal denervation, Dr. Murray Esler of Melbourne, yet the people who designed SYMPLICITY HTN-3 didn’t pay attention. Their failure to apply what earlier findings had taught about the variability of denervation proved especially egregious, as the interventionalists also couldn’t gauge their procedural success because no easy way exists right now to do this.
But these details didn’t slow the first controlled clinical trial. The concept was so ... simple: Insert catheter into renal artery, throw switch and zap, remove catheter. Easy peasy.
I first heard about renal denervation more than 2 years ago, and marveled at the unmitigated hubris to name the first catheter developed for denervation Symplicity, as well as giving that moniker to a series of uncontrolled and controlled studies that tested the technique. The Symplicity crowd seemed very sure of themselves, of this catheter, and of this procedure.
Fast forward a couple of years and the name morphs into the ironic butt of an expensive, failed trial.
If there is anything I’ve learned during more than 3 decades of covering medicine, it’s that the discipline is hardly ever simple. Think of signaling-pathway diagrams, the ones with all the arrows, boxes, and small fonts. The most reliable reaction when confronted in medicine by something that appears simple is to ask: What am I missing here? Hopefully, when this still-promising technology resurrects, its developers will have learned that lesson.
On Twitter @mitchelzoler
