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Renal denervation redeemed itself in the SPYRAL HTN-OFF MED trial, showing real, clinically-meaningful results in patients off blood pressure medications in an interim analysis.

Three months after the procedure, patients showed modest drops in blood pressure from baseline mild-to-moderate hypertension:

• 24-hour systolic (-5.5 mm Hg, P=0.0031)
• 24-hour diastolic (-4.8 mm Hg, P<0.0001)
• Office systolic (-10.0 mm Hg, P=0.0004)
• Office diastolic (-5.3 mm Hg, P=0.0002)

A sham-control group had no such reductions in blood pressure, giving renal denervation the edge statistically in all four measures. Adjustment for baseline differences yielded similar results, according to senior investigator Michael Böhm, MD, of Germany's Saarland University Medical Center, at the (ESC) meeting. The Lancet simultaneously published the SPYRAL HTN-OFF MED data online.

Since participants were off antihypertensive drugs, Böhm called this a "biologic proof of concept for the efficacy of renal denervation". Furthermore, these mostly single-digit magnitudes of blood pressure reduction are "clinically meaningful" as they have been previously associated with reduced cardiovascular/coronary deaths and stroke, he claimed.

"I think the magnitude is a respectable amount, certainly not the large 30-, 20-mm drops in blood pressure that had initially been reported in unblinded, non-sham-controlled trials -- those results surely were exaggerations or just spurious," Deepak Bhatt, MD, of Brigham and Women's Hospital in Boston, told 乌鸦传媒. "But I think here we have a result, while more modest, is at least a real finding." Bhatt was not involved in the study.

Discussant Bryan Williams, MD, of University College London Hospitals, suggested at the ESC late-breaking trial session two groups that would have a real use for renal denervation: patients with high blood pressure that cannot be controlled by drugs, and those with less severe hypertension (the case in SPYRAL HTN-OFF MED) who want to be "cured" with a one-off process that removes the need for long-term drug therapy.

But "would patients wishing to avoid medication view this outcome as a success?" he asked. In all likelihood, the main role for renal denervation would be the former, he said.

Böhm and colleagues conducted their multicenter trial by randomizing 80 patients to renal denervation or sham control (renal angiogram only). This followed an initial screening of 353 individuals with 3-4 week medication washout.

They sought to avoid the pitfalls of the negative trial, which critics suggested was an imperfect trial utilizing an imperfect ablation technique.

"This novel trial differs substantially from previous renal denervation trials in terms of the hypertensive population enrolled, the renal denervation technique used, and the absence of concomitant antihypertensive medications. To our knowledge, this is the first rigorously done sham controlled clinical trial to assess blood pressure reduction in hypertensive patients in the absence of antihypertensive medications," according to the investigators.

SPYRAL HTN-OFF MED required patients to be off antihypertensive medications unless systolic blood pressure exceeded 180 mm Hg within 3 months of randomization. After that, a drug titration protocol was initiated when systolic blood pressure rose past 140 mm Hg. Drug testing showed that 85.5% were compliant with staying off antihypertensives over 3 months.

Renal denervation was performed with Medtronic's new Symplicity Spyral multi-electrode catheter. This device has four electrodes delivering simultaneous radiofrequency ablations on a helical catheter.

Operators were also more aggressive in this study, having gone into branch vessels during denervation (even so, the ablation group had no deaths, MIs, or other major safety events at 3 months).

Böhm noted that the study's focus was on 24-hour ambulatory blood pressure monitoring as the main outcome measure and was not powered for definite conclusions.

"To do a properly powered randomized trial assuming a 5 mm Hg systolic blood pressure reduction with a standard deviation of 12, it was established that 246 patients would be required. Because of the unsatisfactory outcome of the SYMPLICITY HTN-3 trial, we decided to proceed with a smaller, proof-of-concept trial that would minimize exposure of patients to an interventional procedure and provide sufficient evidence to move forward with a larger, powered trial."

New enrollees, starting with the 81st patient, are to be included in such a trial.

"We really need a much larger multicenter trial to confirm these findings. Probably some more tweaking of technique and design as well to try to get a more robust benefit and try to identify which patients might really benefit because within this trial, there seem to be some patients that were responders and others that weren't responders," Bhatt commented.

For example, 28.6% actually had worsened hypertension upon 3-month follow-up.

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