Renal denervation along with use of antihypertensive drugs leads to a sustained reduction in blood pressure for up to 36 months with acceptable safety, investigators reported in The Lancet.
In the single-blind SPYRAL HTN-ON MED trial (ClinicalTrials.gov, NCT02439775), investigators randomly assigned 38 patients to receive radiofrequency renal denervation and 42 to a sham control procedure. Renal denervation delivered radiofrequency energy to overactive nerves in renal arteries and branch vessels. All patients had 24-hour ambulatory systolic blood pressure of at least 140 but less than 170 mm Hg despite stable doses of 1-3 antihypertensive drugs. (The protocol allowed changes in antihypertensive medications after 6 months.) Diastolic blood pressure at baseline was 90 mm Hg or higher.
From baseline to 36 months, mean ambulatory systolic pressure significantly decreased 18.7 mmHg in the renal denervation group compared with 8.6 mmHg in the sham group, Felix Mahfoud, MD, of Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Homburg, Germany, and colleagues reported. Diastolic blood significantly decreased by a mean 5.9 mmHg more in the renal denervation vs sham group. Morning and night systolic blood pressure decreased by a mean 11.0 and 11.8 mmHg more, respectively, in the renal denervation group.
“Radiofrequency renal denervation compared with sham control produced a clinically meaningful and lasting blood pressure reduction up to 36 months of follow-up, independent of concomitant antihypertensive medications and without major safety events,” Dr Mahfoud’s team wrote. “Renal denervation could provide an adjunctive treatment modality in the management of patients with hypertension.”
The authors pointed out that significant decreases in night-time and early morning ambulatory blood pressure at 24 months and 36 months could translate into reductions in cardiovascular events, including stroke and heart failure. “The sustained nature of 24-h blood pressure reduction with renal denervation might be superior to treatments with antihypertensive drugs, which are often associated with non-adherence,” they noted.
Medication burden (considering medication classes and dosages) did not differ significantly between groups at 36 months: 2.13 in the renal denervation group vs 2.55 in the sham control group. Medication adherence at 36 months was lower in the renal denervation group: 77% vs 93%, respectively. The investigators did not assess changes in exercise, diet, or smoking habits.
At baseline, the mean estimated glomerular filtration rate (eGFR) was 82 mL/min/1.73 m2. Changes in eGFR, serum creatinine, sodium levels, and potassium levels from baseline to 24 months and 36 months did not differ between the renal denervation group and the sham control group, the investigators reported.
Major adverse events comprised all-cause mortality, end-stage kidney disease, an embolic event resulting in end-organ damage, renal artery perforation or dissection requiring intervention, vascular complications, hospitalization for hypertensive crisis, and new renal artery stenosis greater than 70%. Over 36 months, 1 patient died in the sham group and 1 stroke and hypertensive crisis occurred in the renal denervation group. No patient experienced renal artery stenosis or re-intervention due to renal denervation. Reinnervation – a concern with renal denervation – also did not occur during the follow-up period.
Among the sham group, 31% later underwent renal denervation as part of protocol-permitted crossover after 24 months. An additional 260 study participants are undergoing randomization as part of the SPYRAL HTN-ON MED Expansion trial.
“In the stark absence of novel antihypertensive drug development, renal denervation is seemingly poised to be an effective supplement, if not an alternative, to complex antihypertensive regimens with frequent dosing schedules,” Harini Sarathy, MD, of the University of California San Francisco and Liann Abu Salman, MD, of the University of Pennsylvania in Philadelphia, wrote in an accompanying editorial. “We look forward to the results of the Expansion trial in providing more definitive answers regarding whether this translates to meaningful protection from target organ damage.”
The editorialists pointed out that although renal denervation appears to effectively lower blood pressure, the renal denervation group “did not quite reach guideline-recommended blood pressure thresholds. This result could have been due to a degree of physician inertia or differential prescribing of blood pressure medications for the intervention group compared with the sham control group, wherein physicians might have considered renal denervation to be the fourth antihypertensive medication.”
Disclosure: This research was supported by Medtronic. Please see the original reference for a full list of disclosures.
Mahfoud F, Kandzari DE, Kario K, et al. Long-term efficacy and safety of renal denervation in the presence of antihypertensive drugs (SPYRAL HTN-ON MED): a randomised, sham-controlled trial. Lancet. Published online April 4, 2022. doi:10.1016/S0140-6736(22)00455-X
Sarathy H, Salman LA. Can renal denervation replace medications for patients with hypertension? Lancet. Published online April 4, 2022. doi:10.1016/S0140-6736(22)00614-6