Medtronic’s SYMPLICITY HTN-3 Long-Term Data Presented

September 18, 2022—Medtronic announced the presentation of long-term results from the SYMPLICITY HTN-3 clinical trial. In the randomized controlled trial, patients who underwent radiofrequency renal denervation (RDN) with Medtronic’s first-generation Symplicity system, had a statistically significant reduction in office and ambulatory blood pressure compared to patients in the sham control group.

Deepak L. Bhatt, MD, coprincipal investigator of the trial, commented in the company’s press release, “In this long-term follow-up from the SYMPLICITY HTN-3 trial, we observed significant reductions in the blood pressures of patients who underwent treatment with RDN, with no long-term complications emerging from this minimally invasive procedure.”

Dr. Bhatt, who is executive director of Interventional Cardiovascular Programs at Brigham and Women’s Hospital and Professor of Medicine at Harvard Medical School in Boston, Massachusetts, further explained, “These findings provide important insights into the evolution of patients’ blood pressure control, with and without RDN, in a scenario more akin to the real-world setting—under everyday physician management without the frequent follow-up visits and monitoring that occur in research settings.”

He concluded, “The results illustrate that for certain patients with high blood pressure, despite attempts to adhere to multiple medications and modify their lifestyles, their blood pressure remains poorly controlled, putting them at risk for cardiovascular complications such as stroke.”

The data were presented in a Late-Breaking Clinical Science session at TCT 2022, the 34th annual Transcatheter Cardiovascular Therapeutics scientific symposium of the Cardiovascular Research Foundation held September 16-19 in Boston, Massachusetts.

The findings were simultaneously published online by Dr. Bhatt, et al in The Lancet.

According to Medtronic, the SYMPLICITY HTN-3 was composed of a total of 535 patients with treatment-resistant hypertension. The patients were randomized 2:1 to RDN (n = 364) or sham control (n = 171). After 6 months, 101 patients in the sham control arm underwent treatment with RDN (crossover group).

The company reported that when conducting a longer-term analysis with all available data, and accounting for control crossover patients by using their last observation carried forward (imputation), the results through 3 years for the RDN group versus the sham-control group are as follows:

• Reduction in office systolic blood pressure of 26.4 mm Hg (RDN, n = 219) versus 5.7 mm Hg (sham, n = 134); adjusted treatment difference of 22.1 mm Hg (P < .0001).
• Reduction in 24-hour ambulatory systolic blood pressure of 15.6 mm Hg (RDN, n = 152) versus a 0.3 mm Hg (sham, n = 119); adjusted treatment difference of 16.5 mm Hg (P < .0001)
• On average, 17.5% of RDN patients versus 8.2% of sham patients spent time in target range (P < .0001).
• The Medtronic Symplicity blood pressure procedure with the first-generation device, which included a single-electrode catheter, demonstrated long-term safety in line with expected outcomes for this patient population.

Medtronic noted that in 2014 the company announced that at 6-months the HTN-3 trial met its primary safety endpoint but did not meet its primary or secondary efficacy endpoints because of multiple confounding factors, including the influence of medication changes, specific patient subgroups, and procedural factors. The full results of the SYMPLICITY HTN-3 clinical trial were presented in March 2014 at ACC.14, the 63rd annual scientific sessions of the American College of Cardiology, and published by Dr. Bhatt et al in The New England Journal of Medicine.

This latest analysis of the SYMPLICITY HTN-3 trial presented at TCT 2022 examined the long-term safety and efficacy of RDN in hypertensive patients who were on antihypertensive medications and received treatment with the Symplicity blood pressure procedure. This included patients from the sham control arm who crossed over to RDN after the initial 6-month primary endpoint analysis.

Jeffrey Popma, MD, chief medical officer for Medtronic’s Coronary & Renal Denervation business and the Structural Heart & Aortic business, commented in the press release, “While we did not find a significant 6-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.”

Dr. Popma continued, “Using standard imputation methods for [blood pressure] comparison in cross-over patients, we were pleased to see a sustained benefit in 3-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.”

Finally, he noted, “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 Symplicity Spyral RDN system is approved for commercial use in more than 60 countries. It is limited to investigational use in the United States, Japan, and Canada, advised the company.