There’s no keeping renal denervation down, it seems, as new data suggest the procedure may be an effective and durable adjunct to hypertension medications.
Conceived after SYMPLICITY HTN-3’s failure to show meaningful benefits in resistant hypertension, the proof-of-concept SPYRAL HTN-ON MED trial has released three-year results showing that radiofrequency renal denervation “significantly reduced” blood pressure long-term, “independent of concomitant antihypertensive medications and without major safety events”.
Funded by radiofrequency ablation device-producer Medtronic and published in The Lancet, the sham-controlled trial assessed efficacy and safety outcomes in 80 patients with uncontrolled hypertension. At baseline, patients had office systolic blood pressure between 150 mmHg and 180 mmHg, diastolic blood pressure of 90 mmHg or higher, and 24-hour ambulatory systolic blood pressure between 140 mmHg and 170 mmHg while on one of three antihypertensive drugs, with stable doses for at least six weeks, the study reported.
It found that although renal denervation and control patients had a similar medication burden at 36 months (mean 2.13 medications versus 2.55 respectively, P = 0.26), the former group had an 18.7 mmHg (standard deviation [SD]: 12.4) reduction in ambulatory systolic blood pressure compared with -8.6 mmHg (SD: 14.6) in sham recipients (adjusted treatment difference: -10.0 mmHg, 95% CI: -16.6 to -3.3, P = 0.0039).
They also had better ambulatory diastolic blood pressure, along with morning and night systolic blood pressure than controls, seeing treatment differences of -5.9 mmHg (95% CI: -10.1 to -1.8, P = 0.0055), -11.0 mmHg (95% CI: -19.8 to -2.1, P = 0.016), and -11.8 (-19.0 to -4.7, P = 0.0017) respectively.
The findings come despite worse medication adherence in the renal denervation group, where 77% (24 of 31) were taking their antihypertensives properly at 36 months versus 93% (25 of 27) in the control group.
While promising, the study and an accompanying editorial acknowledged renal denervation patients still didn’t reach the guideline-recommended 140 mmHg, even though physicians could increase antihypertensive medications after six months.
They suggested three factors may have played a role in missing the target: clinician inertia, differential prescribing in blood pressure medications (where some clinicians may have considered renal denervation a fourth antihypertensive therapy) and patient difficulty tolerating medication increases.
Nonetheless, adverse events were “rare” in the 36-month study period, with one death of unknown cause reported in the sham group and one stroke and hypertensive crisis in a renal denervation recipient.
“There were no instances of renal artery stenosis or reintervention associated with renal denervation” and no differences in eGFR, serum creatinine, sodium or potassium level changes from baseline to three years between the groups, the authors added.
So, does renal denervation have a place in hypertension therapy?
Given the treatment’s apparent efficacy and safety, the study authors and the editorialists suggested renal innervation “could provide an adjunctive treatment modality in the management of patients with hypertension”.
However, the current study had several limitations, not least, its proof-of-concept design with small sample and non-powered endpoints.
Hopes are now focused on the SPYRAL HTN-ON MED Expansion trial, which is randomising 260 hypertension patients to renal denervation or sham treatment, and which will give “more definitive answers” about the procedure’s usefulness in target-organ protection.
It’s thought the progressive blood pressure reduction seen in the current study and others may be driven by “long-term continued remodelling of the vasculature following modulation of the sympathetic nervous system by renal denervation, causing changes in the total peripheral resistance and hence pulse wave reflection”, the trial authors wrote.
“Furthermore, renal denervation alters the activity of the renin angiotensin aldosterone system,” they noted.
So far, there’s been little evidence of significant functional reinnervation in the test cohort, allowing for the sustained blood pressure reductions and easing durability concerns, they suggested.
The morning and night-time reductions could mean less cardiovascular events, including stroke and heart failure, while the 24-hour decrease “might be superior to treatments with antihypertensive drugs, which are often associated with non-adherence,” they said.
The editorialists noted that “severe forms of hypertension and resistant hypertension are difficult to treat and often complicated by polypharmacy and patients’ reluctance or inability to tolerate several antihypertensive medications.”
“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,” they concluded.