Renal denervation for hypertension, initially thought to be a promising procedure, went into disrepute after the publication of the SYMPLICITY HTN-3 trial . But the procedure has staged a potential comeback after the publication of SPYRAL HTN-OFF MED trial .
SYMPLICITY HTN-3 was a prospective, single blind, randomized, sham controlled trial of patients with severe resistant hypertension. Patients were receiving a stable antihypertensive regimen of maximally tolerated doses of at least three anti hypertensive medications including a diuretic. Primary efficacy endpoint was change in office blood pressure at 6 months. The study randomized 555 patients in a 2:1 ratio to renal denervation or sham procedure. Patients were required to have a systolic pressure of 160 mm Hg or more as an average of three measurements.
Radiofrequency energy was delivered using Symplicity renal-denervation catheter. Patients were unaware of whether it was a renal artery denervation or sham procedure. Blood pressure was assessed by persons unaware of the randomization. A composite of major adverse events were taken as the primary safety end point. The events were all cause mortality, end stage renal disease, an embolic event resulting in end organ damage, renal artery or other vascular complications, hypertensive crisis within 30 days or new renal artery stenosis of more than 70% within 6 months.
The blinded SYMPLICITY HTN-3 trial did not show significant reduction of systolic blood pressure in patients with resistant hypertension after 6 months of renal artery denervation as compared to a sham control. There were no significant differences in safety between active treatment and sham control groups. The results of SYMPLICITY HTN-3 trial was in contradiction to that of the unblinded Symplicity HTN-2 trial.
In the Symplicity HTN-2 trial those with immediate renal denervation had a mean fall of 31.7 mm Hg at 6 months and 28.1 mm Hg at 1 year . Those who crossed over to renal denervation from control group had a mean fall of 23.7 mm Hg at 6 months after the procedure. Enrollment criteria for Symplicity HTN-2 were similar to SYMPLICITY HTN-3 trial, but it was unblinded and had a lower number of patients of 106 .
SPYRAL HTN-OFF MED was a proof-of-concept trial evaluating the effect of renal denervation on blood pressure in the absence of medications . It was a multicenter, international, single blind randomized sham controlled trial. Office systolic pressure was between 150 – 180 mm Hg, diastolic blood pressure 90 mm Hg or more. 24 hour ambulatory systolic blood pressure was between 140 – 170 mm Hg at screening. The patients underwent renal angiography and were assigned to renal denervation or sham control. Primary endpoint was change in 24 hour blood pressure at 3 months. Drug surveillance was done to ensure absence of antihypertensive medication. The trial had a total of 80 patients. A fall of 24 hour systolic blood pressure of 5.5 mm Hg and diastolic blood pressure of 4.8 mm Hg was documented in the renal denervation group compared to the sham control group. Corresponding values for office blood pressure was 10 mm Hg and 5.3 mm Hg. These results were statistically highly significant. Thus the authors claim to have established the biological proof of principle for blood pressure lowering efficacy of renal denervation.
SPYRAL HTN-OFF MED Pivotal study randomized 331 hypertensive patients to either renal denervation or sham procedure . Office blood pressure was between 150 – 180 mm Hg. 24 hour systolic blood pressure was lowered by 3.9 mm Hg and office systolic blood pressure by 6.5 mm Hg. There were no device related or procedure related safety events up to 3 months. The authors concluded that SPYRAL Pivotal documented the superiority of catheter-based renal denervation to safely lower blood pressure in the absence of antihypertensive medications.