SPYRAL HTN-ON MED Gives Traction to Renal Denervation Field

Patrice Wendling

May 23, 2018

PARIS — Renal denervation provides meaningful blood pressure reductions in hypertensive patients taking up to three commonly used antihypertensive drugs, according to results from the sham-controlled SPYRAL HTN-ON MED trial.

Patients randomly assigned to renal denervation had a 9.0–mm Hg reduction in 24-hour ambulatory systolic blood pressure at 6 months vs a 1.6–mm Hg reduction for patients in the sham control group (P = .005). Reductions in diastolic blood pressure were also significantly different between groups (6.0 vs 1.9; P = .03).

Office blood pressure was similarly reduced for systolic (9.4 vs 2.6; P = .02) and diastolic (5.2 vs 1.7; P = .048) measures, David Kandzari, MD, Piedmont Heart Institute, Atlanta, Georgia, reported in a hotline session here at the Congress of the European Association of Percutaneous Cardiovascular Interventions (EuroPCR) 2018. The results also were simultaneously published May 23 in The Lancet.

The recent SPYRAL HTN-OFF MED trial provided biologic proof of concept for the efficacy of renal denervation, demonstrating an average 5–mm Hg reduction in 24-hour ambulatory systolic blood pressure vs sham control, but it was unknown how real-world use of antihypertensive medications would affect the catheter-based treatment (Symplicity Spyral, Medtronic).

"It's hard to compare across the trials and we're too early to make definitive statements about the absolute magnitudes that should be expected, but it would almost appear that the renal denervation procedure is complementary to medicines by further increasing the blood pressure," Kandzari told theheart.org | Medscape Cardiology.

"On the other hand, what we saw in this trial were the results at 6 months and in the OFF MED, we saw them at 3 months."

Blood pressure reductions at 3 months were similar in the two trials, but there was a progressive decline between 3 and 6 months with renal denervation in patients on medication, he noted.

"This is a very interesting trial that resuscitates a little bit the technique," panelist Manual Sabaté, MD, Cardiovascular Clinic Institute, Barcelona, Spain, said in an interview. "The main issue to me is that in patients taking up to three antihypertensive drugs, they can get an even higher reduction in blood pressure as compared to the previous trial in patients without drugs."

He observed that recruitment in SPYRAL HTN-ON MED was particularly slow, however, possibly because of prior negative renal denervation trials, such as SYMPLICITY HTN-3 and SYMPLICITY-FLEX. "However, with these results, physicians and patients may be more prone to accept the therapy, and if you have this procedure you can eliminate some, not all, but some medications."

"Always-on" Effect

Investigators at 25 centers enrolled 467 patients with an office systolic blood pressure between 150 and 180 mm Hg and an office diastolic blood pressure of 90 mm Hg or higher at two screening visits who were taking one to three standard antihypertensive drugs with stable doses for at least 6 weeks.

The present analysis includes 38 patients randomly assigned to renal denervation therapy and 42 to the sham procedure, consisting of renal angiography and sensory masking. At baseline, the mean office systolic blood pressure was 164.6 mm Hg and 163.5 mm Hg, respectively, and 24-hour systolic blood pressure was 152.1 mm Hg and 151.3 mm Hg, respectively.

At least half of patients in the renal denervation (53%) and sham-control (52%) groups were prescribed three classes of antihypertensive drugs. Medications use in the trial included diuretics (57.9% vs 59.5%), calcium channel blockers (71.1% vs 73.8%), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (81.6% vs 83.3%), and β-blockers (10.5% vs 14.3%). No patients were on spironolactone.

Medication adherence was about 60% throughout the trial in both groups but "highly dynamic," despite patient education and awareness of drug testing, Kandzari said.

Assessment of systolic and diastolic blood pressure over 24 hours showed persistent and consistent reductions at all time intervals in the renal denervation group. This "all-on" effect may have "important implications distinctive from pharmacotherapies with peak and trough levels in early morning and late evening hours and be of special relevance for individuals at high risk for cardiovascular events," he said.

As observed in the SPYRAL HTN OFF-MED trial, there were no procedural or safety events during follow-up, including major bleeding, vascular complications, new-onset end-stage renal disease or myocardial infarction, renal artery stenosis of more than 70%, or death.

Session co-chair Gabriel Steg, MD, Hôpital Bichat, Paris, France, and Imperial College London, United Kingdom, told theheart.org | Medscape Cardiology, "This is one more stone in the now small hill of evidence we're building regarding renal denervation, that renal denervation seems to be back."

Some may view the 9–mm Hg reduction in blood pressure as not that significant, but from an epidemiological standpoint "it's a huge difference and a huge step forward on top of medication," he said. Also impressive was that ambulatory blood pressure reductions were seen at both daytime and nighttime readings.

For the individual patient, however, this remains a slightly cumbersome procedure that takes a lot of time and uses a lot of contrast and unlike many other interventional procedures doesn't "fix the problem" because patients are still going to need some antihypertensive agents, Steg said.

Among the renal denervation group, an average of 2.3 renal arteries were treated per patient, with a mean procedure time of 60 minutes and mean contrast volume of 270.8 mL. The total number of ablations per patient was 45.9.

"I don't think this is the definitive answer," Steg said. "It indicates that the procedure is alive, but we need to continue to refine it, improve it. We'll probably need some form of tracking success instead of blindly burning tissue and then hoping the blood pressure will come down. Until we get a way to monitor what we're doing, I think that's going to be a limitation of the procedure."

In an editorial accompanying the study, Peter Blankestijn, MD, and Michiel Bots, MD, both from the University Medical Center Utrecht, the Netherlands, write that the two SPYRAL studies are the start of real progress in understanding the effects of renal denervation in hypertension but that additional sham-controlled trials are needed.

"A single intervention with prolonged effect for a condition that is usually without symptoms could mean a significant advancement, but unresolved issues remain, including identification of those patients most likely to benefit, determining the sustainability of effects on blood pressure and safety through long-term follow-up, determining mechanisms of the blood pressure–lowering effect, and developing tests to establish the extent of kidney denervation, among other issues," they write.

In addition, Blankestijn and Bots say it is appropriate to start exploring the technology in other conditions.

"From a pathophysiological point of view, patients with chronic kidney disease, heart failure, certain arrhythmias, and kidney-related pain syndromes should be considered irrespective of the level of blood pressure," they write.

The trial was sponsored by Medtronic. Kandzari reported institutional grant/research support from Biotronik, Boston Scientific, Medtronic CardioVascular, Medinol, and Orbus Neich and receiving fees/honoraria from Biotronik, Boston Scientific, Medtronic CardioVascular, and Cardinal Health. Sabaté and Steg reported having no relevant financial disclosures.Blankestijn reports institutional grants from The Netherlands Organisation for Health Research and Development, Medtronic, Dutch Kidney Foundation, European Commission, Applied and Engineering Sciences, St Jude, and Recor Medical. Bots declares no competing interests.

Congress of the European Association of Percutaneous Cardiovascular Interventions (EuroPCR) 2018. Presented May 23, 2018.

Lancet. Published online May 23, 2018. Abstract, Editorial

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