Renal denervation trial a near miss for resistant high blood pressure

MedTech News: Renal denervation, relative to a sham procedure, was linked with statistically significant reductions in blood pressure in the trial from Medtronic. However, several factors may have prevented the study from meeting its primary endpoint.

Dr David Kandzari, Piedmont Heart Institute and Cardiovascular Services and SPYRAL HTN-ON MED lead principal investigator reported the study results at the recent American Heart Association (AHA) scientific sessions 2022.

The SPYRAL HTN–ON MED pivotal trial followed the previously completed SPYRAL HTN–ON MED pilot study, which did show a significant BP-lowering effect on antihypertensive medications followed radiofrequency denervation. In a recent update of the pilot study, the effect was persistent out to 3 years.

In the pivotal trial reported at the AHA 2022, the average reduction in 24-hour systolic BP in the denervation arm (6.5 mm Hg by 6 months), was in line with recent sham-controlled trials that met their primary endpoints. However, that was not significantly greater than the 4.5-mm Hg reduction seen in the sham arm (P = 0.12). In the primary Bayesian analysis, there was only a 51% probability of renal denervation being superior, far below the threshold for success (97.5%).

Despite differences seen in BP control in favour of renal denervation, several factors were identified that likely contributed to the missed primary endpoint.

More than 80% of patients in the ON MED expansion group did go through follow-up during the COVID-19 pandemic. Based on this data, it appears the difference in outcomes from previous positive SPYRAL trials may be due to changes in the patients’ lives during COVID.

“Significant differences in medication prescriptions were disproportionate in favour of the sham group,” reported Dr Kandzari. He said these differences, which were a violation of the protocol mandate, led to a “bias toward the null” for the primary outcome.

Professor Markus Schlaich, Dobney Chair in Clinical Research at the Dobney Hypertension Centre in WA told Health Industry Hub “Renal denervation has been studied extensively in appropriately designed clinical trials and has been shown to represent a very safe and effective means of lowering blood pressure in a wide range of patients with or without concomitant antihypertensive drug therapy. Most importantly, the effects are sustained up to 9 years (based on our own data), positioning renal denervation as an excellent long-term BP lowering strategy. Renal denervation is a valid third pillar of hypertension management in addition to lifestyle modification and pharmacotherapy.”

An important element in the eventual rollout will be patient preference, Dr Kandzari said, citing research showing that many patients with uncontrolled hypertension despite the use of medications have stated that they would opt for an intervention over an escalation of their medication regimen to lower their BP.

Medtronic said with this additional data, it has submitted the final module of the Symplicity Spyral premarket approval (PMA) application to the U.S. Food and Drug Administration (FDA) for final review.