After two studies indicated that renal denervation lowers blood pressure both with and without antihypertensive drugs, Felix Mahfoud (Klinik für Innere Medizin III, Saarland University Hospital, Homburg, Saarland, Germany) said that the PCR group was “committed to supporting the field of renal denervation”. He added that there would be further developments in the field, so interventional cardiologists should “stay tuned”.
Mahfoud’s statement, on behalf of PCR, came directly after two sham-controlled trials were presented at EuroPCR (22–25 May, Paris, France)—with both studies suggesting that renal denervation does lower blood pressure. The first of these, SPYRAL HTN-ON MED (of which, Mahfoud was an investigator), explored the use of the Symplicity Spyral renal denervation system (Medtronic) in patients with moderate, uncontrolled hypertension who were taking one to three antihypertensive medications. A previous study with the first-generation Symplicity catheter did not demonstrate a significant reduction in blood pressure compared with a sham procedure in patients with resistant hypertension. According to Mahfoud, one of the lessons from this trial was that “we probably started with the wrong population” because their hypertension was too severe and perhaps could not be treated with anything.
Presenting the SPYRAL HTN-ON MED trial at EuroPCR, David E Kandzari (Department of Interventional Cardiology, Piedmont Heart Institute, Atlanta, USA) reported that patients were included in the study if they were stable on one to three antihypertensive medications for six weeks prior to enrolment. After a second screening visit, 80 patients were randomised to renal denervation (38) or a sham procedure (38). Follow-up visits were scheduled at one month, three month, six months, and planned 12 to 36 months after the procedure. The primary efficacy endpoint was change from blood pressure measured at baseline (at the second clinic visit) to blood pressure measured at the six-month follow-up visit.
At six months, there was a significant decrease in 24-hour ambulatory blood pressure in terms of systolic and diastolic blood pressure in the renal denervation group compared with baseline levels. There were no significant blood pressure reductions in the sham procedure group. These findings meant that, compared with the sham procedure group, the renal denervation group had significant reductions in both 24-hour systolic blood pressure and 24-hour diastolic blood pressure: -7mmHg (p=0.0059) and -4.3mmHg (p=0.0174), respectively.
Writing in the Lancet—SPYRAL HTN-ON MED was simultaneously published in the journal to its EuroPCR presentation—Kandzari et al note that the magnitude of blood pressure decline was “clinically significant” as prior studies have shown such reductions to be associated with “both lower rates of both cardiovascular events and mortality”. Kandzari told Cardiovascular News: “Irrespective of the level of blood pressure elevation, the extent of blood pressure reduction observed in this trial has clinical significance. Considering that hypertension is the worldwide leading cause of death and disability, if confirmed in larger study, such blood pressure reductions would have substantial public health impact.”
In the Lancet, the authors observe that the extent of blood pressure reduction with renal denervation “increased over follow-up through six months” and the reductions were present throughout the day and night. Kandzari told delegates at EuroPCR this represents an “always on” effect for renal denervation that may have particular relevance given the limitations of dosing regimens and adherence with medications.
This apparent “always on” effect may be of particular importance given the relative prevalence of patients in both the sham procedure group and the renal denervation group who did not adhere to their medication regimens. Overall, the study investigators report in the Lancet, individual patient adherence to medication was 60% and this was “highly variable”. “We embarked on the SPYRAL HTN OFF MED study as a biological proof-of-principle study [which showed renal denervation to significant lower blood pressure in patients not taking medication]. However, the rates of non-adherence and patients’ general desire not to take medication has increasingly come to the forefront. So, there may be a role for renal denervation in the context of patients off medication,” Kandzari commented.
He concluded: “Renal denervation with the Symplicity Spyral system resulted in statistically significant and clinically relevant blood pressure reductions at six months in uncontrolled hypertensive patients compared with sham control and in the presence of commonly prescribed antihypertensive medications.” In the context of these results, further to the potential use of renal denervation being used in patients off medication, the procedure could be used to compliment drug therapy to lower blood pressure in patients with “uncontrolled hypertension despite the persistent use of medication”.
Following Kandzari’s presentation, Laura Mauri (Brigham and Women’s Hospital, Boston, USA) presented the results of the RADIANCE-HTN SOLO trial (which, like SPYRAL HTN ON MED was simultaneously published in the Lancet). This study compared renal denervation with an endovascular ultrasound system (Paradise, ReCor Medical) with a sham procedure in patients with mild-to-moderate hypertension who were off medication. Mauri reported that, at the two-month follow-up point, renal denervation was associated with a “greater reduction in daytime ambulatory blood pressure than a sham procedure (6.3mmHg greater, p<0.001, in the intention-to-treat analysis), consistent reductions in 24-hour ambulatory, office, and home blood pressure, and a high rate blood pressure control on the absence of medications.”
Both Kandzari and Mauri noted that further studies, of the respective devices, would further evaluate the safety and efficacy of renal denervation. Kandzari reported that a larger SPYRAL HTN PIVOTAL trial is ongoing—having just received investigational device exemption from the US FDA—and would further examine the use of renal denervation in patients off medication. Additionally, he said that “a study design for a larger trial in the presence of antihypertensive therapy is in development”. Mauri stated that follow-up of the RADIANCE-HTN SOLO study is ongoing through three years to assess longer term safety and efficacy of the endovascular renal denervation system and that “enrolment is ongoing for a parallel blinded sham-controlled trial of patients with resistant hypertension (RADIANCE-HTN TRIO)”.
Mahfoud commented that main research topics of these studies and other studies should be intraprocedural feedback, identification of responders, and sustainability of the effects. However, based on the available evidence, he added: “We know that renal denervation does lower blood pressure in hypertensive patients with and without antihypertensive drugs. There is more to come, so stay tuned!”