Where renal denervation stands for the treatment of drug-resistant hypertension

What does renal denervation do? The procedure uses one of several catheter-based technologies in development that kills the sympathetic nerves in the walls of the renal arteries that lead to the kidneys. This is supposed to prevent vasodilation and props the vessels in a wide-open position to increase the filtration of the blood by the kidneys.

"So the latest about denervation is that there have been several sham controlled trials that have come out and demonstrated, in comparison to the sham, renal denervation can lower blood pressure," Kirtane explained. 

This includes data from trials presented at the 2022 Transcatheter Cardiovascular Therapeutics (TCT) and AHA meetings last fall. The data has been centered on the FDA pivotal trials for the Recor and Medtronic denervation systems. Recor's Paradise system uses an endovascular ultrasound catheter to cause denervation. Medtronic's Spyral denervation system catheter turns into a corkscrew shape inside the vessel to press four radiofrequency ablation electrodes against the vessel wall to kill the nerves.

Kirtane presented combined data from three RADIANCE trials for the Recor system at AHA. He said this showed a consistent reduction of hypertension in patients that received denervation compared to the sham procedure after two months. He presented the pivotal RADIANCE-II trial at TCT in September.

UPDATE: FDA approves Recor as the first renal denervation system for uncontrolled hypertension

Durability of the denervation procedure 

Medtronic's initial denervation system used a single point ablation catheter in the SYMPLICITY HTN-3 trial, published in 2014. The trial failed to meet its primary endpoint at six months with comparable results between denervation and medical therapy. This sent the vendor back to the drawing board to develop the Spyral to enable more consistent lesion creation, which is now in trials. 

However, the 3-year data for SYMPLICITY HTN-3 were presented at TCT 2022 and found patients who had the procedure maintained lower blood pressure readings. This appears to show durability for the denervation effect.

"The result of the study was stone-cold negative, there was no difference between the two arms so we have to be cautious when interpreting the results," Kirtane explained. He said the trial had issues with its design, in part because of the first generation technology used at the time.

"What is challenging about these trials is that the medicines work, they lower blood pressure. And, if you do not carefully control the medicines in both groups of patients, it becomes hard to discern a treatment effect. In that trial, blood pressure dropped by 12% in the sham arm, and that was not a sham effect. That was because of the medications being used in patients who were previously not very well controlled," he said. 

This also likely impacted the data in the Spyral HTN - ON MED trial presented at AHA, which also was negative. The primary endpoint was to show that in an on-medication population there would be a difference ambulatory blood pressure, but there was no difference between the groups. 

"That is because in the sham arm more medicines were added back," Kirtane said. "So what was really being studied was denervation plus medications, but with less medication, versus sham plus medication, where more medications were used. And in that construct, it becomes hard to discern a difference. But thankfully office blood pressure was different in favor of denervation."

Renal denervation is not a cure for hypertension

He said what the Recor and Medtronic data presented at AHA show is that the difference between sham and denervation is not massive, something like a 5 to 15 mm/mg difference. This means this is not a cure for hypertension, but an adjunct to what cardiologists are already doing.

"People have to go into this knowing what the blood pressure drop will be, so they don't go into it thinking they are going to be taking patients off of medicines. They will be sorely disappointed because that's not what the study results show," Kirtane explained. 

Patient selection for renal denervation

The data from the RADIANCE trial have been submitted for FDA review, and Medtronic submitted for FDA clearance as well in November 2022. Kirtane said he thinks these technologies will likely be approved in the near future, though it will be up to clinicians to decide how to best implement the technology in clinical practice.

"I don't think we want to get into a clinical scenario where anybody with high blood pressure is sent for denervation. That is not the right way to approach this," Kirtane explained. "The right way to approach this is to systematically engage with clinicians and teach them how to treat hypertension. I had to learn a lot about hypertension, and I thought I knew it and I said 'how hard can blood pressure be?' It's actually not so easy. So we need to educate in that regard and then treat the patients with lifestyle and medications. And if a patient cannot take the medications, or will not take them, or they are not controlled with them, then denervation can be a good option." 

Both renal denervation systems have European CE mark clearance. Both are investigational devices in the U.S. and have not been cleared yet by the FDA.