BARCELONA, SPAIN — Following a series of negative trials that seemed to sound its death knell, renal denervation was shown to significantly lower blood pressure in untreated patients with mild to moderate hypertension, in an interim analysis of the SPYRAL HTN-OFF MED study[1].
Among the first 80 patients, the average 24-hour ambulatory systolic blood-pressure reduction was 5 mm Hg and office systolic blood-pressure reduction was 7.7 mm Hg vs sham control.
The study was not powered for statistical significance but “provides biologic proof of principle for the efficacy of renal denervation” and will inform the design of a larger pivotal trial, co–primary investigator Dr Michael Böhm (University Hospital of Saarland, Homburg/Saar, Germany) reported here at the European Society of Cardiology (ESC) Congress 2017.
Dr Clyde Yancy (Northwestern University, Chicago, IL), who was not involved with the study, told theheart.org | Medscape Cardiology “there’s no reason for exuberance” based on these results.
“We eagerly anticipate new guidelines and expect the target blood pressures will be much lower than they’ve been before and a 5-mm-Hg delta from a baseline of 150 to 160 [mm Hg] will be insufficient,” he said. “Whether or not it will be different when it’s partnered with lifestyle changes or concomitant low doses of other medicines, we don’t know.
“So we can’t become too excited about these data referable to clinical application, but what we can do is accept the fact that these data initiate the conversations again about renal denervation.”
That conversation fell to a whisper in 2014 after the pivotal SIMPLICITY HTN-3 trial missed its primary end point of sustained systolic blood-pressure reduction at 6 months in patients with treatment-resistant hypertension. Böhm, however, pointed out that the two trials are vastly different and that “the technique has completely changed.”
Two Substantially Different Trials
In SIMPLICITY HTN-3, patients had resistant hypertension (office SBP 180 mm Hg, with no diastolic cutoff), self-reported drug adherence to 5.1 medications prescribed at randomization, and received denervation of the main renal artery only performed by mostly inexperienced operators using a monoelectrode, sequential ablation system, Böhm said.
In contrast, SPYRAL HTN-OFF MED enrolled patients with an office SBP of 150 to less than 180 mm Hg, an office DBP of at least 90 mm Hg, and a mean 24-hour ambulatory SBP of 140 to less than 170 mm Hg and excluded those with isolated systolic hypertension because they’ve been shown to be hyperresponsive to renal denervation.
In addition, the procedure was performed by highly experienced operators using a four-electrode, simultaneous ablation system (Symplicity Spyral, Medtronic) and was extended beyond the main artery into renal-artery branch vessels, leading to a fourfold increase in ablations per patient (43.8 vs 11.2), he said.
Finally, drug testing of serum and urine confirmed that 94.3% of patients in the renal-denervation group and 92.7% in the sham control group were not on antihypertensive medications.
For the primary end point of change in 24-hour ambulatory blood pressure from baseline to 3 months, SBP dropped by 5.5 mm Hg in the renal-denervation group (P=0.003) and 0.5 mm Hg in the sham-control group (P=0.76), while DBP declined 4.8 mm Hg (P<0.001) and 0.4 mm Hg (P=0.65).
Office readings showed SBP fell 10.0 mm Hg with denervation (P<0.001) and 2.3 mm Hg with sham (P=0.24), while DBP declined 5.3 (P<0.001) and 0.3 mm Hg (P=0.81).
No major adverse events were reported in either group.
Clinically Meaningful Changes?
Böhm said the blood-pressure changes were clinically meaningful and in a simultaneous online publication of the study in the Lancet, the authors note that a recent meta-analysis[2] predicts a roughly 20% reduction in the relative risk of CV events with a 7.7-mm-Hg sham-adjusted reduction in office SBP.
Invited discussant Prof Bryan William (University College London, UK) agreed that the data provide proof of concept that renal denervation lowered blood pressure in “about 75% of patients studied” but said by excluding those with isolated systolic hypertension it missed “the most common and most difficult-to-treat hypertension phenotype.”
He also noted that there was a large sham effect and large variability in those who responded, despite more standardized treatment delivery with a multielectrode. Indeed, in 10 patients, blood pressure actually increased after denervation.
Based on the reduction in ambulatory SBP from an average of 154 to 148 mm Hg and in office-based SBP from 162 to 152 mm Hg, patients treated with denervation would still need to take medications to achieve currently recommended BP treatment targets, which are only likely to go lower with revision of guidelines around the world, he said.
“I would ask the question: would patients wanting to avoid medications by having an intervention view this outcome as a success?”
The study was funded by Medtronic. Böhm reports consulting for Abbott/St Jude, AstraZeneca, Medtronic, Servier, and Vifor; and grant support from Medtronic, Servier, and the German Research Foundation. Disclosures for the coauthors are listed in the paper. Yancy reported no relevant financial relationships. Williams reported consulting for Vascular Dynamics, Novartis, and Relypsa/Vifor.
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