Long-term efficacy and safety of renal denervation in the presence of antihypertensive drugs (SPYRAL HTN-ON MED): a randomised, sham-controlled trial
- The Lancet 2022;399(10333):1401-1410
What was known?
Renal denervation has been shown to lower blood pressure in the presence of antihypertensive medications, but long-term safety and efficacy data from randomised trials are missing and challenging to obtain due to factors such as variance in medications, and unblinding status among patients and health-care providers.
This pre-specified analysis of the SPYRAL HTN-ON MED study aimed to test the hypothesis that renal denervation reduces blood pressure in the presence of up to three antihypertensive drugs.
What this study adds:
Long-term safety and efficacy data of renal denervation in a population already on antihypertensive medications.
The positive results of this trial suggest that renal denervation could be an effective adjunctive treatment to antihypertensive medication in patients with uncontrolled hypertension.
SPYRAL HTN-ON MED was a randomised, multicentred, international, single-blind, sham-controlled trial (NCT02439775) that enrolled patients with uncontrolled hypertension and office systolic blood pressure (SBP) of 150–180 mmHg and diastolic blood pressure (DBP) of ≥90 mmHg, despite taking one to three antihypertensive medications for at least 6 months. After renal angiography, patients were randomly assigned to either radiofrequency renal denervation or a sham control procedure. Sham control patients were able to cross over after 12-month follow-up completion.
- The treatment difference in mean 24-h SBP at 6 months in the renal denervation vs. sham control groups
- Change in SBP as measured by 24-hour Ambulatory Blood Pressure Monitoring
- Changes in (office) SBP or DBP at 36 months post-procedure
- Long-term safety up to 36 months using a composite endpoint of major adverse events
- Office SBP ≥ 150 mmHg and <180 mmHg and office DBP ≥ 90 mmHg
- Mean 24-h SBP ≥ 140 mmHg and < 170 mmHg
- Taking 1-3 antihypertensive medication classes
Notable exclusion criteria:
- Lack of appropriate renal artery anatomy
- Estimated glomerular filtration rate <45
- Type 1 diabetes mellitus (DM) or uncontrolled type 2 DM
- Individuals with ≥ 1 episodes of orthostatic hypotension or primary pulmonary hypertension
- Stable or unstable angina within 3 months of enrolment, myocardial infarction within 3 months of enrolment; heart failure, cerebrovascular accident or transient ischemic attack, or atrial fibrillation at any time
- 80 patients were randomised to the renal denervation (n=38) or sham control (n=42) groups
- Despite a similar intensity of antihypertensive drugs, ambulatory SBP and DBP were significantly reduced and were lower in the renal denervation group at 24 and 36 months
- The medication burden (mean ± standard deviation) at 36 months were 2.13 ± 1.15 and 2.55 ± 2.19 medications in the renal denervation and sham control groups respectively (p=0.26)
- At 36 months,
- drug adherence was greater in the sham control group vs. renal denervation group (93% vs 77%)
- ambulatory SBP reduction was –18.7 ± 12.4 mmHg and –8.6 mmHg ± 14.6 in renal denervation and a sham control procedure respectively [adjusted treatment difference, –10.0 mmHg; 95% confidence interval (CI), –16.6 to –3.3; p=0.0039]
- significant treatment differences between the two groups were –5.9 mmHg (95% CI, –10.1 to –1.8; p=0.0055) for mean ambulatory DBP, –11.0 mmHg (95% CI, –19.8 to –2.1; p=0.016) for morning SBP, and –11.8 mmHg (95% CI, –19.0 to –4.7; p=0.0017) for night-time SBP
- No safety issues associated with renal denervation were reported
At 24- and 36-months post-procedure, significant reductions in 24-h SBP and DBP with a favourable safety profile were observed in patients who underwent renal denervation compared with those who had a sham control procedure, despite similar antihypertensive drug use. Therefore, renal denervation could be considered as an effective treatment option in patients with uncontrolled hypertension.
- Blood and urine testing were not required at 12 months
- Changes in patients’ exercise, diet, or smoking habits were not assessed
- No specific blood pressure criteria were required for the purpose of crossover
- A low percentage of women was enrolled in this study
- Long-term results were specific to radiofrequency renal denervation and might not be generalisable to other renal denervation procedures