Expansion of trial with RDN in patients on hypertensive medication

AHA 2022 The SPYRAL HTN-ON MED pilot trial was expanded resulting in a larger cohort of patients on hypertensive medication who underwent radiofrequency renal denervation (RDN) or sham treatment. What was the change in systolic ABPM after 6 months between the two groups?

Presented at the AHA Scientific Sessions 2022 by: David Kandzari - Atlanta, GA, USA

Introduction and methods

A catheter-based renal denervation (RDN) procedure targets the sympathetic nervous system to lower blood pressure (BP). Previous sham-controlled trials showed significant lowering of BP with radiofrequency RDN in the absence and presence of antihypertensive medication (SPYRAL HTN-OFF MED Pivotal and SPYRAL HTN-ON MED Pilot), with long-term data of SPYRAL HTN-ON Med up to 3 years.

This study examined the outcomes of RDN in the presence of antihypertensive medication in an extension cohort in an international sham-controlled RCT.

In the SPYRAL HTN-ON MED Expansion trial, 257 patients were enrolled with uncontrolled hypertension (office SBP ≥150 to <180) who were prescribed 1 to 3 antihypertensive medication classes. Patients were randomized in a 2:1 ratio to a renal denervation group and a sham control group. There were 80 patients in the PILOT cohort, resulting in an ON MED Full Cohort of 337 patients.

In the ON MED PILOT study, a significant difference favoring RDN was found for 24h systolic ABPM (7.3 mmHg) and office systolic BP (6.6 mmHg).

The primary efficacy outcome was the 6-month change in 24h systolic ambulatory BP (ABPM). Primary safety endpoint was major adverse events at 1 month in pooled trials (SPYRAL HTN-OFF and ON MED).

Main results

Safety outcomes

• Prevalence of adverse events at 6 months was low in both groups (2 events of vascular complications in the RDN group and 1 event of vascular complications and 1 new stroke in the control group).
• In the pooled trial population of SPYRAL HTN-OFF and ON MED with 253 patients treated with RDN, 1-month adverse event rate was 0.4%.

Efficacy outcomes

• 24h Systolic ABPM was reduced by 6.5 mmHg in the RDN group and by 4.5 mmHg in the sham control, a non-significant difference of 1.9 mmHg (P=0.12).
• Office SBP was reduced by 9.9 mmHg in the RDN group and by 5.1 mmHg in the sham control group, a difference of 4.9 mmHg (P=0.001).
• There was a difference of 0.8 mmHg for 24h diastolic ABPM between the RDN and sham control groups after 6 months (P=0.37) and a difference of 2.0 mmHg for office diastolic BP between the groups (P=0.04), favoring RDN procedure.
• After 6 months, number of medications and medication burden (based on number, class and dosage) was significantly lower in the RDN group than in the sham group (P=0.01 and P=0.04, respectively).
• There was substantial differences in ABPM outcomes between the Pilot and Expansion cohorts. Therefore, only 19.4% of data from the Pilot study could be borrowed from the RDN arm and <1% from the sham arm for a Bayesian analysis, that basically represents the Expansion cohort. The 52% probability of superiority did not meet the Bayesian threshold for success (97.5%).

Exploratory analyses

• Statistically significant in the patterns of ABPM were identified for daytime systolic ABPM (P=0.033), nighttime systolic ABPM (P=0.001) and overall 24h systolic ABPM (P=0.001) between pre-COVID and during COVID groups.
• There was a significant net medication change after 6 months in favor of BP reduction between the RDN group and sham control group (percentage of patients with change: 21.8% vs. 1.9%, P<0.0001) in the ON MED Expansion cohort, and this was not observed in the ON MED Pilot cohort.
• In a win ratio analysis with change in 24h SBP ≥5 mmHg and change in med burden, RND was favored with a win ratio of 1.50 (P=0.005).

Conclusion

In the SPYRAL HTN-ON MED Full cohort population, there was no significant change in systolic ABPM after 6 months between the RND and sham control groups. Office BP however was more reduced in the RND group after 6 months than in the sham control group. Furthermore, the primary safety endpoint across SPYRAL HTN trials was met with low incidence of procedural-related and clinical adverse events.

- Our reporting is based on the information provided at the AHA Scientific Sessions 2022 -

Read our summary of SPYRAL HTN-ON MED