▎ WuXi AppTec content team editor
In the management of hypertension, some patients may need to take multiple antihypertensive drugs at the same time, and these patients may have poor adherence to medication, difficulty taking medications completely according to the guidelines, or may not be effective despite existing drug therapy. For patients with refractory hypertension, we clearly need other antihypertensive methods.
As a minimally invasive surgical therapy to lower blood pressure, renal sympathomics (RDN) has previously shown its safety and efficacy (with or without pharmacotherapy) in patients with mild to moderate hypertension. Recently, the long-term positive effects of this therapy in patients with refractory hypertension have finally been confirmed!
The results of a long-term follow-up study called SPYRAL HTN-ON MED showed that RDNs could bring clinically significant and sustained blood pressure reductions to patients over a follow-up period of up to 36 months, and that the therapeutic effect was not related to the concomitant use of antihypertensive drugs. The results of the relevant important trials were announced at the 71st Annual Meeting of the American College of Cardiology (ACC 2022) and published in The Lancet.
Screenshot source: THE LANCET
Increased sympathetic excitability is an important neural mechanism that causes hypertension, and RDN can play a role in lowering blood pressure by ablating neurons involved in blood pressure regulation in the renal arteries. Previous studies have shown that RDN is still able to exert a hypotensive effect in hypertensive patients who receive antihypertensive drugs. However, until now, there is a lack of randomized trial data on RDN to confirm its long-term safety and efficacy.
The SPYRAL HTN-ON MED study is a randomized, single-blind, pseudo-controlled trial designed to assess differences in blood pressure, antihypertensive drug use, and safety in hypertensive patients under RDN or sham surgery. The main endpoint of the study was the difference in efficacy of 24-hour mean systolic blood pressure at 6 months between the RDN group and the sham surgery group (published in 2018, and the results showed that the 24-hour mean systolic and diastolic blood pressure, office systolic and diastolic blood pressure in the RDN group were higher than in the sham surgery control group).
Based on the 3-year follow-up data of the SPYAL HTN-ON MED study (including ambulatory blood pressure/office blood pressure, safety event data, etc.), the long-term efficacy and safety assessment results of RDN treatment were announced.
The study enrolled 467 patients from 25 medical centers in the United States, Germany, Japan, the United Kingdom, Australia, Austria, and Greece whose blood pressure remained substandard after taking antihypertensive medications (systolic blood pressure in the clinic was 150 to 180 mm Hg; diastolic blood pressure exceeded 90 mm Hg). Of these, 80 patients met the final inclusion criteria for the study (140 to 170 mm Hg at 24 hours of dynamic systolic blood pressure, taking a stable dose of 1 to 3 different antihypertensive drugs for at least 6 weeks), and randomized radiofrequency ablation RDN (38 cases) or sham control surgery (42 cases) in a 1:1 ratio after renal angiography.
The results of the study showed that in the 24th and 36th months after surgical treatment, although the intensity of antihypertensive therapy drugs received by the two groups of patients was similar, the average dynamic systolic and diastolic blood pressure in the RDN group not only had 24 hours of all day, morning, daytime and night, but also the systolic and diastolic blood pressure in the clinic was significantly reduced compared with the baseline, and the decline rate showed an increasing trend. At the same time, the decrease in blood pressure indicators was more significant in the RDN group compared with the sham surgery control group.
After 36 months of surgical treatment, the dynamic systolic blood pressure reduction was -18.7 mm Hg (SD=12.4) in the RDN group (n=30), -8.6 mm Hg (SD=14.6) in the sham surgery control group (n=32), and the corrected difference in treatment was -10.0 mm Hg (95% CI: -16.6 to -3.3; p=0.0039）。 Dynamic systolic blood pressure (p=0.002) was < 140 mm Hg (p=0.002) in the RDN group and 14 patients (43.8%) in the RDN group and control group, respectively.
▲ 24-hour dynamic systolic blood pressure changes in two groups of patients at baseline to ground 36 months (Image source: Reference[1])
In addition, the difference in treatment of mean dynamic diastolic blood pressure between the RDN group and the sham surgical control group was -5.9 mm Hg (95% CI: -10.1 to -1.8; p=0.0055); the difference in morning systolic blood pressure treatment was -11.0 mm Hg (-19.8 to -2.1; p=0.016); difference in nocturnal systolic blood pressure treatment was -11.8 mm Hg (-19.0 to -4.7; p=0.0017）。
In terms of medication, after 36 months of surgical treatment, the types of medication for patients in the RDN group and the sham surgery group were 3.03 and 3.05 respectively (p=0.76). Of the 31 patients in the RDN group, 24 (77%) were still taking antihypertensive medications, while 25 (93%) of the 27 patients in the sham surgery control group were still taking medications. In terms of security, current studies have not observed short- or long-term security issues associated with RDNs.
Overall, the current "Long-term follow-up results of the first sham-operated controlled randomized trial" further confirm that radiofrequency ablation RDNs can result in a clinically significant sustained decrease in blood pressure in patients at long-term follow-up compared with sham surgery, and that the therapeutic effect is not related to the co-use of antihypertensive drugs. At the same time, no major safety incidents occurred in patients with radiofrequency ablation RDN surgery.
The authors emphasize that the results of the SPYRAL HTN-ON MED study show that RDN has long-term safety while exerting a long-lasting antihypertensive effect, and RDN is expected to become an important supplement to drug therapy!