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  • Long-term efficacy and safety of renal denervation in the presence of antihypertensive drugs (SPYRAL HTN-ON MED): a randomised, sham-controlled trial

Long-term efficacy and safety of renal denervation in the presence of antihypertensive drugs (SPYRAL HTN-ON MED): a randomised, sham-controlled trial

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.

Objective(s):

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.  

Clinical implications:

The positive results of this trial suggest that renal denervation could be an effective adjunctive treatment to antihypertensive medication in patients with uncontrolled hypertension.

Study design:

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 150180 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.

Primary endpoints:

  • 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  

Secondary endpoints:

  • 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

Inclusion criteria:

  • 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

Findings:

  • 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

Interpretation:

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.

Limitations:

  • 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