A combination of findings presented at ACC 2014 and a newly published clinical paper, point to a bleak future for Renal Denervation as a blood pressure reducing therapy, at least as far as Medtronic’s Symplicity System is concerned.
The ACC presentation has been much anticipated since January’s announcement that Medtronic’s Symplicity HTN-3 study had missed its primary outcome endpoints. The finding that this therapeutic solution, that had promised so much in earlier studies, was nothing like as effective in a sham controlled study, sent shockwaves through the specialty and the industry alike. For Covidien it was all too much, signalling the end of the game for them, despite having made a sizeable acquisition within the last twelve months. Boston Scientific and St. Jude said they would wait and see, hoping that the results might have an explanation that would allow their own devices to claim efficacy. After all, the study data presented from HTN-3 and a newly published New England Journal of Medicine (NEJM) study only looked at Medtronic’s first generation Symplicity device.
So where are we now, after a pivotal few days for Renal Denervation? Well, sadly for its advocates, things don’t appear to have got much better. While Medtronic continues to sound hopeful, it’s also openly acknowledging that it is looking at other applications including atrial fibrillation.
Perhaps more enlightening than the ACC presentation was the actual NEJM paper, which eloquently underlined the lack of impact from the therapy and discussed why this might be so different to earlier nonrandomized studies and randomized, unblinded trials which showed large reductions in blood pressure, as measured at an office visit, after renal denervation. It points out that the the Symplicity HTN-3 study was carefully designed to overcome methodologic shortcomings that included small sample sizes, limited assessment of ambulatory blood pressure, lack of blinding, and lack of a sham procedure as a control, all factors which could make broad application of the findings unreliable.
Of course the authors point to the uniquely sham controlled nature of the study. The conclusion has to be that a number of factors are at play here. Certainly not least is the possibility that by undergoing an invasive procedure, the control group were themselves experiencing a combination of placebo effect, coupled with an enhanced adherence to medication and dietary regimes as a result of the increased gravity experienced by going through an invasive treatment.
So we’re left with no statistically observable effect, an expressed need for further studies and the hope that HTN-3’s failure to demonstrate efficacy might prove to be more about the device than the therapy. Here again there’s doubt though. After all, while the study didn’t look for evidence that denervation had been effected, angiographic evidence suggests it had, and the Symplicity system confirmed that energy had been delivered.
It’s going to be interesting to see what happens now. Will the other players capitulate?
And there remains the question of what this all means for the international clinical fraternity that has already adopted the therapy. Study author Deepak Bhatt said; “As far as clinical practice outside the U.S., I think doctors need to look at these data and honestly ask themselves, is their clinical practice so dissimilar from the patients in our trial that they would not believe a rigorously done, randomized clinical trial? Personally, I would be cautious about offering the procedure to patients in the face of a large, randomized clinical trial.”
NEJM study here