Dr Justin E. Davies speaks to Cardio Debate and Radcliffe Cardiology about Renal denervation in 2015 during the ESC 2015 in London, UK.
Transcript – Renal denervation in 2015
Where is renal denervation following the SIMPLICITY-HTN3 trial?
I think renal denervation post-SIMPLICTY-HTN3 is in a very exciting place. SIMPLICTY-HTN3 results were disappointing initially, but what they really did was they caused us to have a good look at the data, a good look at the background to the whole process of renal denervation – both encompassing the patient selection and the tools we used – and then how to apply these more effectively moving forwards.
And now we’ve got a series of studies that are about to start, looking at renal denervation. We’ve refined who we’re going to do the procedure in, we’ve refined the procedure more, and importantly we’ve also controlled more carefully for the drug which patients are on to ensure we have the best possibility of getting a pressure drop with the technique and also with the minimum degree of variability, which is very important for clinical trial design.
So overall I hope in the next 18 months to two years we’ll see a series of studies that will re-explore this therapy and hopefully show that there is a true benefit to denervation in terms of lowering blood pressure.
Has the technique been applied correctly in clinical practice?
Well certainly people asked after HTN3 if there were technical problems with the application of the denervation therapy itself. I think this is one perhaps that we don’t know all the answers to.
Certainly we can see that there are some geographical differences between the results which people get. But we also know that the technologies themselves have advanced and improved over the last 12 months.
We now have most catheter systems, which rather than doing a single denervation at each individual location on the vessel, apply multiple burns simultaneously. And of course this offers the hope that we have of wider coverage of denervation, and better contact with the wall. And also we have more of a helical pattern, which we know gives the best chance of having successful denervation.
Are there sub-groups of patients who would be better suited to renal denervation?
One of the big learning things that we found from the HTN3 study is that there are certain groups that potentially could benefit more.
Probably one of the biggest groups that would benefit from denervation therapy are patients who have an elevated diastolic blood pressure. Or put another way these are patients without isolated systolic hypertension.
If you just have an elevated systolic pressure and your diastolic pressure is low, we know that these patients are less likely to benefit from renal denervation therapy.
And we think the mechanism for this is that if your diastolic pressure is low and you have systolic hypertension you tend to have a very stiff aorta. Now renal denervation itself cannot change the anatomy, calcification levels which are in the aorta itself.
However if your diastolic pressure is raised in addition to having a high systolic, then your resistance often in the peripheral vessels is higher, and the denervation itself, by reducing sympathetic tone, can cause dilatation of these vessels, reducing diastolic pressure and of course bringing both your systolic and mean pressure down.
So this patient population, to identify these, is very important. And most of these studies moving forward now have got an exclusion criteria of having a diastolic pressure above a certain high threshold. This is very important.
One of the other areas where people looked at after HTM3 and were very interested in was the effects of different racial groups, particularly as the African American population appeared not to have as big a response.
I think that now we’ve looked at this data more carefully, we don’t necessarily think that it’s one racial group or another. But perhaps it is other things associated with different racial groups. It may well be where they live, socioeconomic status, and this may influence pharmacological prescribing and drug taking patterns.
We know from looking at the HTN3 data that there are certain geographies in the United States, whether you are African American or Caucasian, you have very good blood pressure results.
In others, the differences appear bigger between the African American and Caucasian groups. And what tends to follow the differences in this two different groups and geographies is wealth.
So it really follows socioeconomic patters very, very closely. So rather than essentially excluding one group or another, moving forward, we know that it’s likely that the socioeconomic patterns alter the pharmacological compliance of these patients.
So we know studies, going forward, are going to pay very close attention to ensuring that patients have good compliance. Making sure they are taking their medications, checking it using urine screening, and in some of the studies making sure they are off all drugs alone so we can exclude drugs as a potential confounder of the studies and just look in the purest form to see if renal denervation causes blood pressure to fall.