Following positive study results from Medtronic and Recor at the Transcatheter Cardiovascular Therapeutics (TCT) conference, renal denervation treatment for resistant hypertension is back in the spotlight. But after a decade of failures and scepticism, are these results enough to finally convert physicians?
The encouraging data presented by the companies found that patients receiving renal denervation (RF RDN) for resistant hypertension had a statistically significant reduction in blood pressure compared to subjects in sham control groups.
In ReCor’s RADIANCE II IDE pivotal trial, 1038 patients were screened for eligibility at study centres in eight countries. Around 224 patients with uncontrolled hypertension were randomised 2:1 to ReCor’s Paradise renal denervation system or a sham. Patients were asked to remain off antihypertensive medications throughout the 2 months of follow-up unless specified blood pressure criteria were exceeded.
At the 2-month primary efficacy endpoint, patients treated with the system had a mean reduction in daytime ambulatory systolic blood pressure of 7.9 mmHg, compared to a reduction of 1.8 mmHg in the sham arm. Similar reductions in blood pressure were observed in night-time and 24-hour measures, as well as measurements taken at home and in clinic.
For Medtronic, a long-term follow-up for its Symplicity HTN-3 trial also reported significant reduction in the blood pressure of patients who underwent treatment with renal denervation, with no long-term complications emerging from the procedure.
“After the data presented at TCT, we have more support for renal denervation because previous results did not convince physicians about the technology,” Oscar Mendiz, Director of the Cardiology and Cardiovascular Surgery Institute and Chief of Interventional Cardiology at Favaloro Foundation University Hospital, Buenos Aires, Argentina tells Medical Device Network.
“Now the focus needs to be on collecting additional data and convincing physicians of the clinical outcome. The technique will not be for everyone, but I am strongly convinced and believe that it can be a change for the treatment of resistant hypertension. The important lesson we have learned and need to share is that in many patients we don’t see the change in blood pressure improve immediately but over time.”
The new results may boost confidence as some clinical trials only reported office-based blood pressure reductions, when ambulatory blood pressure readings are seen as a more accurate assessment of hypertension compared to office-based blood pressure readings.
“While we did not find a significant six-month blood pressure reduction difference in RDN versus sham in HTN-3, we felt that there was much to learn by following HTN-3 patients for a longer time period, particularly in those sham patients with sustained blood pressure elevations who ‘crossed over’ to RDN,” said Jeffrey Popma, chief medical officer for Medtronic’s Coronary & Renal Denervation business.
“Using standard imputation methods for blood pressure comparison in cross-over patients, we were pleased to see a sustained benefit in three-year blood pressure reduction in HTN-3 patients treated with RDN. This study adds important, incremental information to the totality of evidence now supporting the long-term effect of RDN in patients with hypertension. Documentation of medication compliance and improvements made to the new Spyral catheter may have the potential to further influence clinical outcomes in patients enrolled in the SPYRAL portfolio of studies.”
The future for RDN
Since the catheter-based interventional procedure first emerged over a decade ago, it has struggled to make significant inroads in blood pressure control. More than 1 billion people worldwide suffer from hypertension, but the primary treatments are still lifestyle changes and medication.
Medtronic’s clinical journey in the space has been particularly troubled. In 2014, the company announced that at six-months the HTN-3 trial met its primary safety endpoint but failed to meet the primary or secondary efficacy endpoints due to medication changes, specific patient subgroups, and procedural factors.
“Combined, with more than 7,000 patients published in clinical studies, we now have a greater understanding of patient behavior and RDN impacts over the long-term,” said Jason Weidman, senior vice president and president of Medtronic’s Coronary & Renal Denervation business. “This analysis adds to the extensive long-term, sham-controlled evidence for the Symplicity blood pressure procedure that has consistently shown a positive impact for patients, both in the absence and presence of medications. We remain deeply committed to this adjunctive hypertension treatment option and look forward to data from additional studies, including the SPYRAL HTN-ON MED extension trial, which we plan to have at the American Heart Association Scientific Sessions, subject to acceptance.”
There are 18 renal denervation devices in various stages of manufacturing and clinical trials. However, many of these trials were put on hold at the beginning of the Covid-19 pandemic. According to GlobalData’s most recent analysis, the renal denervation catheter market is expected to reach $316.2 million by 2030, with growth in the market derived primarily through companies expanding into additional indications and seeking approval in emerging countries such as Brazil and Japan.
One of the most difficult barriers to adoption that medical device companies will face is reimbursement due to regulator concerns over long-term safety and efficacy of the procedure. A second barrier will be the establishment of a completely new referral pattern as renal denervation is performed by interventional cardiologists and radiologists who are not the first line of interaction with hypertension patients.
Once resistant hypertension is diagnosed, a patient will be referred to a hypertension specialist or cardiologist who can then make a final referral for the procedure. The medical device companies that can extend their sales and marketing reach to reach primary care physicians are set to have the most success in shaping this new treatment.