SPYRAL CLINICAL DATA MEDTRONIC RENAL DENERVATION PROCEDURE

SPYRAL HTN GLOBAL CLINICAL PROGRAM

SPYRAL HTN Global Clinical Trial program is a multi-phase clinical strategy designed to isolate and demonstrate the efficacy and safety of the renal denervation procedure. The program includes the SPYRAL HTN-ON MED and SPYRAL HTN-OFF MED trials. SPYRAL HTN is a global study program, with patients randomized across sites in the United States, Europe, Japan, Australia, and Canada.

SPYRAL HTN-ON MED

This study was designed to evaluate the effect of renal denervation (RDN) in the presence of anti-hypertensive drugs, which may be considered representative of clinical practice where integrating drug and procedural strategies may be anticipated.

DR. DAVID KANDZARI ON MED DATA PRESENTATION

Dr. David Kandzari, Interventional Cardiology, SPYRAL HTN-ON MED Lead Principal Investigator, presents the latest results from the ON MED trial.

Blood Pressure Chart

There were statistically significant reductions in 24-hour systolic ambulatory blood pressure and office systolic blood pressure between the RDN and sham groups.1 The 24-hour systolic ambulatory blood pressure declined by 9.0 mmHg in the RDN group, resulting in a statistically significant difference with the sham control arm.1  At 6 months, office systolic blood pressure declined 9.4 mmHg in the RDN group, resulting in a 6.8 mmHg difference with the sham control arm.1 

Equally important, the RDN procedure demonstrated favorable safety. No cases of new or worsening renal failure2, vascular complications3, or other major adverse events were observed within 6 months post procedure4,5. The results confirm the safety of the RDN procedure using the Spyral technology — even with a revised procedural approach that extended ablations into the distal renal artery and branch arteries.1,4

Adverse event (number of events) at 6 months RDN (n=38) Sham Control (n=42)

Death

0

0

New myocardial infarction

0

0

Major bleeding (TIMI1)

0

0

New onset end stage renal disease

0

0

Serum creatinine elevation > 50%

0

0

Significant embolic event resulting in end-organ damage

0

0

New renal artery stenosis > 70%

0

0

Vascular complications

0

0

Hospitalization for hypertensive crisis/emergency

0

0

New stroke

0

0

It is worth noting the consistent reductions in both office and ambulatory systolic and diastolic pressure found in the ON MED trial reaffirmed the blood-pressure-lowering effects observed previously in the sham-controlled SPYRAL HTN-ON MED trial, and extended those findings to patients prescribed anti-HTN medications.1

SPYRAL HTN-OFF MED

SPYRAL HTN-OFF MED trial is a randomized sham-controlled study examining the effect of RDN on hypertensive patients who have been washed off of their medications or are medication naive. The goal of this trial is to explore the effect of RDN alone (without drugs) and controlling for placebo effect and variable medication adherence.

PROF. BÖHM OFF MED DATA PRESENTATION

SPYRAL HTN-OFF MED trial lead investigator, Prof. Michael Böhm, presents the latest results from the OFF MED trial.

- (14:32)

Blood Pressure 3 Month Chart

At three months, patients treated with RDN (n=37) saw significant (p=0.02) reductions in both office blood pressure and 24-hour ambulatory blood pressure compared with patients who received the sham procedure (n=36).4

These safety results were achieved even as a number of ablations were performed in the renal artery branches as well as the main artery. The reductions in blood pressure seen with RDN in this trial correspond to an approximate 20% risk reduction in major cardiac events.1

Number of major adverse effects at 3 months RDN (n=38) Sham Control (n=42)

Death

0

0

New myocardial infarction

0

0

Major bleeding

0

0

New onset end stage renal disease

0

0

Serum creatinine elevation > 50%

0

0

Significant embolic event resulting in end-organ damage

0

0

Vascular complications

0

0

Hospitalization for hypertensive crisis/emergency

0

0

New stroke

0

0

GLOBAL SYMPLICITY REGISTRY

  Real-world results of renal denervation through 3-years.

The Global Symplicity Registry was designed to confirm the safety of the system in real-world data set representative of Flex and Symplicity Spyral in a variety of patient populations. GSR is the single largest real-world study of RDN patients. The procedure was shown to be safe in this large patient set (197 patients) with blood pressure reductions sustained out to 3 years in both office systolic blood pressure as well as 24-hour ambulatory blood pressure monitoring (ABPM). ABPM is regarded as the most scientifically rigorous measure of blood pressure as it reduces single, point-in-time bias and white-coat effect while also incorporating nighttime readings, when dipping or nondipping patterns can be assessed.  

Blood Pressure 2 Year Chart

GLOBAL SYMPLICITY REGISTRY SUBGROUP RESULTS

In GSR high-risk subgroups, patients with diabetes, elderly, ISH, rHTN, and CKD, RDN showed similar consistent and meaningful long-term BP lowering effects between ~10 to 20 mmHG reductions out to three years.

RDN’s BP lowering effect in subgroups is similar to overall patient results. 

GSR Subgroup Resistant HTN and Elderly Populations
GSR Subgroup Diabetic and ISH Populations
GSR Subgroup CKD Population

Safety Results

There were also no long-term safety concerns for subgroups, with adverse event rates similar or better than patients with severe, uncontrolled hypertension (<0.05% restenosis rate, preservation of eGFR).7

Adverse Events at 3 Years All patients
(n=1588)		 Resistant
HTN (n=1053)

Age

≥ 65
(n=684)

 Diabetic
(n=608)		 ISH
(n=613)		 CKD
(n=366)

Death

5.4

5.4

9.1

6.9

6.5

9.3

Cardiovascular death

2.9

2.8

4.7

4.1

4.1

5.5

Myocardial Infarction

2.6

2.3

2.5

4.1

2.8

3.3

Stroke

4.3

4.5

5.0

3.5

4.6

6.3

End-stage renal disease

1.6

1.6

2.0

2.8

2.4

5.7

Creatinine elevation >50%

1.6

1.6

1.6

2.6

1.6

3.3

New renal artery stenosis >70%

0.3

0.4

0.1

0.2

0.3

0.3

Hospitalizations for HTN crisis

3.0

3.3

3.1

3.3

4.2

4.9

SPYRAL FIM

The Symplicity Spyral™ multi-electrode renal denervation catheter is an innovative device from Medtronic for uncontrolled hypertension. It is specifically designed to deliver low-level radio frequency (RF) energy through the wall of the renal artery to achieve renal denervation (RDN). Initial positive results for the efficacy and safety of the Symplicity Spyral™ catheter were reported in the SPYRAL First-in-Man (FIM) study. The single arm SPYRAL FIM6 study showed blood pressure reductions maintained in patients out to a year.

Blood Pressure 12 Month Chart
1

Ettehad D, Emdin CA, Kiran A, et.al., Lancet 2016; 387: 957-67

2

Safety data reported for Symplicity SpyralTM cathether with n=351 enrolled, n=327 at 1-yr, n = 231 at 2-yr, n = 132 at 3-yr. All data on file at Medtronic

3

Mahfoud F, et al. Presented at EuroPCR. 2018. Vascular complication rate was 0.9%, 1.0%, 1.1%, 0% at 6-mo, 1-yr, 2-yr, 3-yr, respectively.

4

Townsend RR, et al. Lancet. 2017;390:2160–2170. 

5

Kandzari DE, et al. Lancet. 2018;391:2346–2355.

6

Whitbourn R, Symplicity multi-electrode radiofrequency renal denervation feasibility system. EuroIntervention. 2015 May; 11(1): 104-9.

7

Mahfoud F, Three-year Safety and Efficacy in the Global Symplicity Registry: Subgroup Analyses. EuroPCR 2019

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