RADIANCE-HTN: Six-Month Outcomes of a Randomized Trial of Renal Denervation Versus a Sham Procedure for Resistant Hypertension – Impact of Treatment-Blinded Medication Titration
Reported from TCT 2021
Panos Xaplanteris review the RADIANCE-HTN Study, presented by Ajay Kirtane, an international randomized, sham-controlled clinical trial evaluating the safety and efficacy of renal denervation (RDN) in a population of treatment-resistant hypertensive patients.
Why this study – the rationale/objective?
Resistant hypertension, defined as above-goal elevated blood pressure (BP) despite the concurrent use of 3 antihypertensive drug classes, represents a therapeutic challenge and results in increased cardiovascular risk.Renal denervation (RDN) catheter-based procedures hold the potential of lowering BP values, thus providing a useful adjunct to medications. The initial promising results of previous studies of RDN were subsequently put into question by sham controlled randomized trials.
How was it executed – the methodology?
The RADIANCE-HTN study is an international randomized, sham-controlled clinical trial evaluating the safety and efficacy of renal denervation (RDN) in a population of treatment-resistant hypertensive patients.
- Patients aged 18–75 years with office BP of at least 140/90 mm Hg despite three or more antihypertensive medications including a diuretic were eligible
- Eligible patients were switched to a once daily, fixed-dose, single-pill combination of a calcium channel blocker, an angiotensin receptor blocker, and a thiazide diuretic. After 4 weeks of standardised therapy, patients with daytime ambulatory blood pressure of at least 135/85 mm Hg were randomly assigned (1:1) to ultrasound RDN or a sham procedure
- RDN was achieved by means of an ultrasound emitting balloon inflated in the renal arteries; the thermal damage produced by the sonification resulted in the diminution of renal nerve activity around the treated arteries
- Addition of antihypertensive medications was allowed if specified blood pressure thresholds were exceeded
- The primary endpoint was the change in daytime ambulatory systolic BP at 2 months; safety was also assessed
- Patients and outcome assessors were blinded to treatment
- 136 patients (average age 53 years; 80% men) were randomized to either RDN or a sham procedure
What is the main result?
The 2-month results of the trial were recently reported (Azizi et al. Lancet 2021). In brief, RDN resulted in a greater reduction in ambulatory systolic BP as compared to the sham procedure (median between-group difference of -4.5 mm Hg, adjusted P value = 0.022). Regarding ambulatory systolic BP, the median between-group difference was -5.8 mm Hg (adjusted P value = 0.0051). Safety outcome data did not differ between groups.
Extending these data, Ajay Kirtane (Columbia University, USA) presented the 6-month outcomes of the trial at TCT 2021. Patients that still had uncontrolled home BP (>= 135/85 mm Hg) at 2 to 6 months after randomization were further given escalated antihypertensive therapy in order to achieve adequate BP control, with spironolactone being the first escalation step. The medication burden, ambulatory, home and office BP were compared between the two groups at 6 months.
Patients randomized to the RDN procedure were less likely to receive spironolactone at 6 months as compared to patients having received the sham procedure (40% versus 60.9%, P value = 0.017). Of note, the percentage of aldosterone antagonist use multiplied from the 2 to the 6-month time point (from 3% to 40% in the RDN group and from 11% to 61% in the sham group). Medication adherence did not differ between the groups, with 71% of RDN patients being fully adherent at 6 months versus 78% of sham (P value= 0.41).
As regards BP measurements at 6 months, the mean home systolic BP was significantly lower by -4.28 mm Hg (P value = 0.027) for the RDN group compared to the sham group. However, the -2.95 mm Hg difference of office systolic BP did not achieve statistical significance. Data from the ambulatory 24-h BP recordings showed similar systolic and diastolic BP reductions for both groups at 6 months by approximately -12 and -8 mm Hg. Similarly, the percentage of patients achieving adequate BP control with RDN was numerically, but not statistically higher, as judged by home, daytime, 24h and office BP readings (P values of 0.061, 0.396, 0.168 and 0.520 respectively).
Coming to the safety outcomes of the procedure, the estimated glomerular filtration rate was similar between groups at 6 months, and there was no difference in major adverse events or other prespecified safety events, including pain lasting for > 2 days, coronary events, hypertensive crises, cerebrovascular events or renal injury.
Critical reading and the relevance for clinical practice
Taken together, these results confirm and extend the favorable safety and efficacy features of RDN at 6 months using the Recor ultrasound device for the treatment of resistant hypertension. The addition of a sham procedure arm allows for a more rigorous, unbiased evaluation of the effects of RDN.
Nonetheless, this trial is single, not double blinded, as only patients and assessors of outcomes (not treating physicians) were blinded to treatment. In the setting of resistant hypertension, which represents the most difficult subset of hypertension to treat by medications alone, RDN can be a useful adjunct and result in further BP reduction. Importantly, this can be achieved by smaller increases in additional medications prescribed, notably aldosterone antagonists.
The discrepancy between home, office and 24-hour BP reduction is interesting, highlights that these measures are not interchangeable but complementary and brings yet again the issue of medication adherence and polypharmacy into question. As patients were directly observed taking their prescribed medication prior to their office and 24-hour BP recordings (thus, optimal adherence at that day), this might partially explain why no differences were observed between groups for these readings, as opposed to home BP readings.
Whether the BP-lowering effect of RDN persists over time, as well as the need for further medication escalation, remain to be proven in the subsequent follow-up of these patients. In addition, it is currently unclear if the additional reduction in home, but not office or ambulatory BP with RDN can result in meaningful favorable clinical outcomes in the long run.
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