Pivotal trial of targeted renal denervation to treat hypertension SMART study

Dr. Ömer Işık

Presented congress: EuroPCR 2023

Link: https://www.crtonline.org/presentation-detail/new-powerpoint-115

BACKGROUND

Hypertension is a condition characterized by irregular blood pressure in the body and affects all systems and organs. 95% of hypertension is essential and there is no single etiology or pathophysiologic mechanism responsible for hypertension. Half of the patients receive inadequate treatment and blood pressure regulation is not achieved in approximately 25% of patients despite triple drug therapy including diuretics. Renal afferent sympathetic stimuli from the kidneys release epinephrine and norepinephrine from the central nervous system. Hyper stimulation of this system results in increased NA uptake, decreased renal flow and glomerular filtration, and increased renin release, resulting in hypertension with the activation of the renin angiotensin system.Renal denervation is based on the disconnection of the kidney from the central nervous system, which plays an important role in hypertension.

OBJECTIVE

The SMART study in China aimed to determine how much the blood pressure of patients would decrease with the renal denervation method and whether all or part of the patients' antihypertensive drugs would be discontinued.

Metod

The SMART study, conducted in 15 centers in China, included 219 patients (mean age 45 years, 87% male) with essential hypertension and uncontrolled blood pressure despite taking at least two antihypertensive drugs. Denervation was performed using the SyMapCath I catheter and SYMPIONEER S1 stimulator/generator (SyMap Medical Ltd).

Operators applied electronic stimulation within the renal arteries to look for points associated with an increase in systolic BP of more than 5 mm Hg. These spots were then ablated, while other areas were left alone. Additional stimulation was applied after ablation to ensure that denervation was achieved.

Results

Baseline systolic office blood pressure averaged 159 mm Hg in both groups, with a mean decrease of 25.2 mm Hg in the denervation group and 27.3 mm Hg in the control group. The majority of patients in both groups reached the target (95.4% in the denervation group and 92.7% in the control group, respectively).The difference between the groups was 2.69% and met the non-inferiority criteria.

The drug index increased in both groups, suggesting that more drug or higher doses were needed to achieve BP control, although the increase was significantly less in the denervation arm (4.37 vs. 7.61; P = 0.003).

In terms of safety, there were no deaths and no cases of severe renal dysfunction in either group. One patient in the denervation arm developed renal artery stenosis. The rate of serious adverse events was 10.8% in the denervation arm and 9.2% in the control arm (P=0.823).

For the primary endpoint, denervation resulted in a significantly greater reduction in office systolic BP at 6 months than sham procedure (mean 25.2 vs 6.2 mm Hg; P < 0.001). There were also significantly greater reductions in office diastolic BP and 24-hour systolic and diastolic BP.

Patients treated with denervation were more likely to achieve a target office systolic BP of 90 to 140 mm Hg (64.7% vs 7.7%) and a decrease of at least 5 mm Hg in office systolic BP (93.4% vs 60.0%; P < 0.0001 for both).

The rates of serious adverse events related to the device or procedure were generally low and there were no cases of renal artery stenosis. One patient in the denervation arm had renal artery dissection, but this was angiography-related, not device-related.

DISCUSSION

He pointed out that the reduction in blood pressure achieved in this study was significantly lower than that seen in other recent studies. This could be for three reasons. First, the patients were relatively young and had no cardiovascular risk factors, and previous studies have shown greater benefit from renal denervation in this population. Second, a standardized two-drug regimen was used in all patients and only 19 patients had an adjustment during the trial, thus minimizing potential variation in medication use. Third, the unique six-electrode design of the device, which provides full circumferential ablation, may explain the degree of BP lowering.

Noting that it is unclear what is behind the large blood pressure reduction seen in this study, it is difficult to know whether it is related to device design or something else without one-to-one comparisons with other denervation systems.In the SMART study, the system involving mapping of the renal arteries followed by ablation of the identified hotspots was shown to provide blood pressure control with less use of anti-hypertensive drugs, but not lower than in the control arm.