Told you so? Well, not quite.
But back in November, researchers from the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London, London, UK, were predicting rather less impressive reductions would evidence themselves when studies appeared that were blinded and measured ambulatory rather than office based blood pressure (BP). Medtronic’s Symplicity HTN3 trial was the first sham-controlled study, but was still office based, so the fact that it sounds like no significant BP reduction was achieved compared with the sham cohort will even be a shock to the London team who had predicted reductions of nearer 12 points rather than the 30 seen in previous studies in resistant hypertensive patients with 160mmHg starting BP.
So what’s going on? How can a treatment that so demonstrably delivered significant and sustained BP reduction, suddenly spit out results that suggest it’s all a giant placebo effect? It simply doesn’t stack up when set alongside placebo-controlled drug studies which identify a reduction in effectiveness when patients are blinded to the treatment, but only a reduction…not an eradicati0n.
So what should investigators and commentators be pointing to? The London team said the degree of blood pressure reduction has a wide range of reported values in other studies. They explain this by suggesting there could be differences in the technical method of achieving renal denervation. This has to overlap into the way the study is conducted and how measurements are collected. For example, they point out that office blood pressure measurements, despite this being a routine daily procedure, have relatively poor test–retest reproducibility. Add to that the study setting and suddenly RDN-treated patients in unblinded trials may just possibly fall foul of the operators urge to remeasure any values that appear clinically inconsistent. With a treatment like renal denervation, which is a lot sexier than a drug study and leaves more physical evidence of it having been performed, that effect could have been amplified.
Then there’s the Symplicity system itself. The device being used in this study is a single electrode, the first generation of renal denervation device and a country mile away from the more sophisticated multi-electrode offerings that have superceded it. Indeed, one investigator has already suggested that the failure of the trial could have been related to this particular denervation system, although again one wonders why this wouldn’t have been picked up in the international markets where these things are available. Still, it’s a theory…
“It was technically difficult to assure that the radiofrequency probe was oriented correctly and that it was touching the wall of the renal artery,” commented Cindy Grines, MD, of Detroit Medical Center. “This may have resulted in the energy being dissipated into the bloodstream instead of into the vessel. Also, the nerves are very deep and the energy level may not have been high enough to penetrate.”
Manufacturers of the so-called “next generation” devices, potentially including Medtronic itself, will no doubt be focusing on the theory that other renal denervation systems could have fared better in the trial. They’ll all be hoping so, as will medtech enthusiasts who have hitherto been unrestrained in their excitement that the industry had delivered a real game changer in the treatment of one of the biggest killers of our day.
What happens next is that Medtronic, with its newly forming expert panel, will be getting pretty forensic with the HTN3 study. Our guess is that renal denervation is a story still only part told. After all, nobody’s yet explained exactly how it works.
For now, we’re fighting the urge to say that when something looks too good to be true, it usually is.
published: January 13, 2014 in: Cardio, Clinical Studies/Trials, medlatest Editorial, Vascular