adjusting phenytoin dose based levels

Renal denervation for hypertension continues its comeback tour after bombing in a 2014 trial. New evidence suggests that it can augment the blood pressure (BP) reductions achieved with aggressively stepped-up antihypertensive therapy in patients who hadn’t responded well to first-line agents.

The finding comes from extended follow-up of a study that had previously seen renal denervation therapy produce meaningful declines in BP, elevated despite initial fixed-dose triple-drug therapy, over 2 months. Importantly, the ultrasound-based ablative therapy used in the blinded trial was compared with a sham control procedure.

In the next stage of the trial, called RADIANCE-HTN TRIO, patients in both the renal denervation and control groups at 6 months showed further BP reductions after stepwise intensification of antihypertensive therapy, generic bystolic next day no prescription starting with an aldosterone antagonist. Mean ambulatory systolic BP dropped by 11.8 mmHg and 12.3 mmHg, respectively, in the 136-patient trial.

Still, home-measured systolic BP fell 4.28 mm Hg (P = .027) more in the denervation group, despite their “smaller increase in additional prescribed medications and less use of aldosterone antagonists” compared with the sham-control group, said Ajay J. Kirtane, MD, SM, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian/Columbia University Irving Medical Center, New York City.

The trial’s 6-month outcomes suggest that antihypertensive therapy according to a standardized stepped-care, medication-escalation protocol can amplify the BP-lowering effects of renal denervation for at least 6 months after the procedure, Kirtane said when presenting the findings at Transcatheter Cardiovascular Therapeutics (TCT) 2021. The conference was held virtually and live in Orlando, Florida.

“It’s notable that the sham group had further and dramatic reductions in blood pressure with the initiation of aldosterone antagonists,” evidence that “lifestyle modification and pharmacotherapy, especially as shown in this trial, are effective and standard of care for the treatment of hypertension,” Kirtane noted.

Still, he went on, “despite best efforts to institute these interventions, patients might not be able to tolerate them or may not adhere to them,” such that their drug-resistant hypertension persists and cardiovascular risk worsens.

“We feel that renal denervation can offer an additional but not a replacement option to further lower blood pressure, especially for patients whose blood pressure is uncontrolled despite genuine attempts to institute conventional therapies.”

The findings are welcome “because they add to the totality of the evidence for renal denervation, suggesting — at least in this instance — intermediate-term durability with renal denervation and also the opportunity to reduce medication burden,” David E. Kandzari, MD, chief of the Piedmont Heart Institute in Atlanta, Georgia, said at a media briefing held prior to Kirtane’s TCT 2021 presentation.

“The opportunity to reduce medication burden,” he said, “is one of the key drivers of patient motivation for an alternative therapy approach like renal denervation.” Kandzari, who was not involved in RADIANCE-HTN TRIO, was principle investigator for the sham-controlled SPYRAL HTN-ON MED renal denervation trial.

“I’m not so sure that we have proven durability here, with the small numbers of patients in this trial,” Roxana Mehran, MD, Mount Sinai School of Medicine, New York City, said at the same press conference.

“But I think it’s a very exciting next step, and to me, it’s opening a window. Previously, the doors might have been closed for renal denervation. I think the window is opening and that it may be a large one.”

As Previously Reported

RADIANCE-HTN TRIO entered adult patients up to age 75 years at 53 centers on both sides of the Atlantic who had BP 140/90 mmHg despite multiple antihypertensive meds. They were put on the same regimen consisting exclusively of one daily pill containing the calcium channel blocker amlodipine; an angiotensin receptor blocker, either valsartan or olmesartan; and hydrochlorothiazide.

The 136 patients with an ambulatory BP of 135/85 mmHg or more after a month of treatment with the triple pill, signifying drug-resistant hypertension, underwent angiography and were assigned to renal denervation therapy (69 patients) or to a sham control procedure (67 patients).

After 2 months of follow-up, during which patients and clinicians were blinded to treatment group, ambulatory systolic BP had fallen a mean of 8 mmHg in those who had undergone renal denervation with triple-drug therapy. That was 4.5 mmHg further than in the sham-control group (P = .022).

Months 2 to 6

Step 1 of the prespecified stepped-care antihypertensive treatment approach consisted of spironolactone at 25 mg/d. Bisoprolol 10 mg/day was added as step 2 for patients not adequately responding to the aldosterone antagonist. Later steps included centrally acting alpha-2 agonists and alpha-1 receptor blockers.

Patients in the denervation and control groups on average added 0.7 and 1.1 medications, respectively (P = .045), during the stepped-care process.

“This was largely reflected in that step-1 initiation of aldosterone antagonists,” which were used in 40% of renal-denervation patients and 61% of the sham-control group, Kirtane said.

The sham control patients were on “disproportionately higher” dosages of spironolactone; so not only were more of that group taking the aldosterone antagonist, but they were also “on it at higher doses to try to achieve the same level of blood pressure reduction.”

No important safety issues were seen, including untoward reductions in estimated glomerular filtration rate (eGFR), Kirtane said.

Renal denervation therapy in RADIANCE-HTN TRIO was conducted using the Paradise Ultrasound Renal Denervation System (ReCor Medical), which is market approved in Europe but not the United States. It is under evaluation in the RADIANCE-2 Pivotal Study of patients with uncontrolled hypertension and will be submitted for regulatory premarket review in the United States, the company said.

RADIANCE-HTN TRIO was funded by Recor Medical. Kirtane disclosed receiving institutional funding from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, ReCor Medical, and Neurotronic; and reimbursement for travel or meals from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, ReCor Medical, Chiesi, OpSens, Zoll, and Regeneron. Kandzari reported minor consulting honoraria from the interventional device industry and institutional research grant support. Mehran disclosed receiving fees or honoraria from Medscape/WebMD, Janssen, and Cine Med Research; that she, her spouse, or her institution have received grants or have other relationships with Abbott Vascular, AstraZenca, Bayer AG, Bristol-Myers Squibb, CSL Behring, Daiichi-Sankyo/Elil Lilly and Company, Medtronic, Novartis Pharmaceuticals, OrbusNeich, CERC, Chiesi, Concept Medical, Applied Therapeutics, Beth Israel Deaconess, Zoll, Arena, Biosensors, Boston Scientific, CellAegis, Insel Gruppe AG, Philips, and Transverse Medical; and that she, her spouse, or her institution hold equity in Elixir Medical, Applied Therapeutics, and ControlRad.

Transcatheter Cardiovascular Therapeutics 2021: Late-Breaking Clinical Science Session I. Presented November 4, 2021.

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