New support for using time in target range (TTR) to assess the clinical impact of renal denervation and lifetime burden of disease in patients with uncontrolled hypertension comes from two analyses presented at EuroPCR 2022.
Between 6- and 36-month follow-up in the Global SYMPLICITY Registry, the major adverse cardiovascular event (MACE) rate was 2.9% in patients who spent more than 50% in TTR compared with 6.2% for patients with a TTR below 50% and 10.3% for those who spent no time in TTR (P < .0001).
The association with higher TTR held true for each component of the endpoint: cardiovascular death (1.5% vs 3.5% and 4.0%), myocardial infarction (0.8% vs 1.5% and 2.0%), and, particularly, stroke (0.1% vs 2.4% and 5.4%).
In multivariate analysis, each 10% increase in TTR was associated with a 16% lower relative risk for MACE. The relative risk was reduced 10% for cardiovascular death, 14% for MI, and 23% for stroke.
“So, important improvements in outcome associated with TTR and this provides the link between this technology and improvements in outcomes,” said Felix Mahfoud, MD, Saarland University Hospital, Homburg/Saar, Germany, during a hotline session devoted entirely to renal denervation.
Several studies have shown that renal denervation reduces blood pressure (BP) in patients with uncontrolled hypertension but skeptics say the observed reductions are modest and question their effect on clinical outcomes.
The present analysis was based on 3077 patients treated with radiofrequency renal denervation (Symplicity Spyral or Flex; Medtronic). Office systolic BP was reduced 13.2 mm Hg at 6 months and 16.7 mm Hg by 3 years, and 24-hour ambulatory BP by 7.3 mm Hg and 9.0 mm Hg, respectively.
TTR, defined as a target office systolic BP of 140 mm Hg or less and/or 24-hour ambulatory BP of 130 mm Hg or less based on linearly interpolated readings during follow-up, increased from 30.6% at 6 months to 34.9% at 3 years. On average, patients spent 377 days in TTR at 3 years, up from only 55 days at 6 months. The improvement occurred without an increase in medications, which averaged 4.85 at 6 months and 4.79 at 3 years, Mahfoud noted.
Fellow presenter David Kandzari, MD, Piedmont Heart Institute, Atlanta, noted that TTR independently predicted MACE in a recent post hoc analysis from the SPRINT hypertension trial. TTR is also a validated measure of control in chronic diseases like diabetes, where over time testing has shifted from office blood glucose and HbA1c levels to sophisticated technologies with continuous monitoring and real-time treatment.
“It’s time that we start thinking about the burden of disease for hypertension in an analogous way because we’re still largely focused on the point-of-care measurement, the blood pressure in the office setting,” he said.
TTR, Kandzari added, “may serve as one additional, very predictive surrogate for clinical outcomes, which have been called for in the space of renal denervation.”
His analysis focused on TTR in 38 renal denervation and 42 sham-control patients in the SPYRAL HTN-ON MED trial, which reported its 3-year results last month.
When TTR was defined as an office systolic BP of 140 mm Hg or less, 28% of the renal denervation group and 13% of the sham group achieved control at 3 years (P = .015), up from 8.1% and 0.6%, respectively, at 6 months (P = .019).
When TTR was defined as an ambulatory systolic BP of 140 mm Hg or less, 47.8% of the denervation group and 32% of the sham group were optimally controlled at 3 years (P = .036), up from 22.2% and 10.4%, respectively, at 6 months (P = .043).
Higher TTR was achieved with a medication burden that was similar, if not higher, in the sham group, Kandzari noted. Medication adherence, based on blood and urine testing and medication prescriptions, was 77% in the denervation group and 93% in the sham group at 36 months.
“The greater stability of BP control and the continued improvement of control over longitudinal follow-up after renal denervation is supported by an ‘always-on’ effect, differentiating this particular therapy for hypertension with the variabilities of drug pharmacokinetics, dosing regimens, and issues related to patient adherence,” Kandzari said.
Pooled RADIANCE Analysis
Rounding out the session was a pooled patient-level analysis of patients with resistant hypertension on initial fixed-dose triple-drug therapy in RADIANCE-HTN TRIO and patients with mild to moderate hypertension off medications in RADIANCE SOLO, of whom 143 underwent ultrasound renal denervation (Paradise, ReCor Medical) and 139 underwent a sham procedure.
The average number of antihypertensive drugs at screening was 2.5 in both groups. At 6 months, physicians needed to add fewer medications to achieve control in the renal denervation group than the sham control group (mean difference, –0.4; P = .001).
In linear regression that adjusted for number of medications, treatment arm, and baseline value, the mean between-group difference was –4.8 mm Hg in daytime ambulatory systolic BP and –5.4 mm Hg for home systolic BP, both favoring renal denervation (P < .001).
There was no heterogeneity of effect in terms of blood pressure reduction or the reduction in medication burden, said Ajay Kirtane, MD, New York-Presbyterian/Columbia University Irving Medical Center, New York City, who presented the results virtually.
“In showing this, we demonstrate that the response to ultrasound renal denervation is consistent across differing severities of hypertension and, further, similar in the presence or absence of medications,” he said. “We think that’s an important finding and, combined with the rest of the data you’re going to hear today, a good message for our patients to hear.”
In response to an audience question on whether renal denervation cures hypertension, Kirtane said “converging data across programs shows that, no, this doesn’t cure hypertension but is a complement to the already defined therapies we have, such as lifestyle modifications and drug therapies.”
During the panel discussion, Michel Azizi, MD, PhD, Université Paris-Descartes, France, emphasized that the pooled analysis focused on ambulatory BP and that a 5 mm Hg drop in this measure is quite large, as studies suggest the average reduction observed with ambulatory BP is 70% of the reduction seen in office BP.
In terms of clinical outcomes, he said, meta-analyses show that a sustained 5 mm Hg drop in office systolic BP is associated with relative reductions of 10% in major cardiovascular disease, 13% in stroke, and 5% in cardiovascular deaths.
“So, saying that 5 millimeters of mercury is a small thing is not real,” Azizi said.
Medtronic sponsored the Mahfoud and Kandzari studies. Mahfoud reports research grants from the Deutsche Forschungsgemeinschaft, Deutsche Gesellschaft fürKardiologie, and Deutsche Herzstiftung; and scientific support and/or speaker honoraria from AstraZeneca, Bayer, Boehringer-Ingelheim, Medtronic, Merck, and ReCor Medical. Kandzari reports institutional research/grant support from Biotronik, Boston Scientific, Cardiovascular Systems, OrbusNeich, Teleflex, Medtronic, and Ablative Solutions; and consulting honoraria from Ablative Solutions, Cardiovascular Systems, Magenta-Medical, Medtronic, and Terumo. Kirtane reports institutional funding from numerous companies; consulting for IMDS; and travel expenses/meals from Medtronic, Boston Scientific, Abbott Vascular, CSI, Siemens, Philips, ReCor Medical, Chiesi, OpSens, Zoll, and Regeneron.
Congress of the European Association of Percutaneous Coronary Interventions (EuroPCR) 2022. Presented May 17, 2022.