VIDEO: SYMPLICITY HTN-3 and the future of renal denervation

When the first results of the trial were presented in 2014, it failed to meet its primary and secondary endpoints. However, long-term tracking of SYMPLICITY HTN-3 patients found the therapy actually did have a positive and durable results several years after initial therapy. Bhatt said there appears to have been a Hawthorne effect on the patients with regular follow-up, with nurses regularly reminding them to take their medications.

However, after the initial six month part of the trial concluded and long-term followup continued, these regular reminders disappeared and many patients became non-compliant about taking medications. It was this factor that showed how well patients actually responded to the denervation procedures, where their hypertension was kept in check. The same was not true in the sham control patients who did not receive denervation. 

"There were some positive signals in the initial SYMPLICITY HTN-3 paper from 2014, where there were some sub-groups that it looked like renal denervation really did work," Bhatt said. "We showed in a later Hypertension article that the nighttime systolic blood pressure was significantly different than the overall trial. We also found in patients who received a more complete ablation with the older ablation catheter, had greater blood pressure response."

Bhatt said these positive long-term results may potentially be met with some skepticism. But, he noted, other sham-controlled renal denervation trials published since the 2014 results of SYMPLICITY also show lasting results from the therapy. 

One of the issues with SYMPLICITY HTN-3 trial was technology used. The original Medtronic Symplicity catheter had a single ablation electrode, and the operator had to move it around to several locations to create different ablation points that kill the renal sympathetic nerves. This prevents the renal arteries from constricting and permanently props them fully open to increase kidney filtration. However, it can be difficult to get a complete ablation of the nerves using a point-by-point ablation system. 

Bhatt said the newer version of the technology, Medtronic's Symplicity Spyral, has four electrodes that create a more consistent ablation around the circumference of the vessel when the catheter is curled into a corkscrew-like configuration inside the vessel. The newer catheter also simplifies and shortens procedure time.

The spiral design was partly a response that came out of the reset caused by the negative trial data in 2014, he said.

"We went back to the drawing board to prefect the catheter and perfect the techniques," Bhatt explained. He said that reset also caused a closer look at patient selection in subsequent renal denervation trials. 

He said the positive long-term data from SYMPLICITY HTN-3 is reassuring because it adds more evidence for the therapy and helps show a parallel to a class effect of a therapy often seen in drug trials. 

Bhatt said he believes the clinician evidence shows support for renal denervation in specific types of patients and it will be included in the armamentarium to treat drug-resistant hypertension patients into the future. He also supports a more open interpretation for which patients should be considered for the therapy. 

"I would say adjacent populations, those not necessarily meeting the strict definition of resistant hypertension, should also be considered," Bhatt explained. "This should include folks with poorly controlled or uncontrolled hypertension, regardless of how they got there. Because even if they are not taking the meds they should, or are eating more salt than they should, the reality is if they come into the emergency room with their blood pressure at 200 over 110, yeah, you can tell them again to take all their medications, cut back on the salt and lose weight. But that patient has a big risk for stroke and other cardiovascular complications, and they are maxed out on drugs and lifestyle modification, doing the best they can. That is real life. Maybe that is the sort of patient this technology can really help."

Read more details on the two late-breaking renal denervation trials presented at TCT in the article Renal denervation lowered blood pressure in two late-breaking TCT trials.