Renal Sympathetic Denervation in Patients With Treatment-Resistant Hypertension After Witnessed Intake of Medication Before Qualifying Ambulatory Blood Pressure

Abstract

A pproximately 10% of patients treated for hypertension remain with uncontrolled high blood pressure (BP), despite prescription of antihypertensive drugs.1 Renal sympathetic denervation has been introduced as a new treatment of hypertension apparently resistant to drug treatment.2 However, it has been known for decades that poor drug adherence is a major problem among these patients. 3,4 It is unknown to what degree the decline in BP after renal denervation (RDN) 2 is caused by denervation itself or concomitantly improved drug adherence. We aimed to investigate for the first time the BP lowering effect of RDN in treatment-resistant hypertension after witnessed intake of medication just before qualifying ambulatory BP. Methods Study Design and PatientsPatients referred specifically for RDN from hospitals and specialist practices in the southern part of Norway (n=18) after publication of the Symplicity HTN-2 study 2 were worked up in the nephrology outpatient clinic at Oslo University Hospital, Ullevål in the time period from December 2011 through June 2012. Treatment-resistant hypertension was defined as uncontrolled hypertension (office systolic BP >140 mm Hg), despite regular intake of maximally tolerated doses of ≥3 antihypertensive drugs, including a diuretic. In addition, patients had to qualify by having mean ambulatory daytime systolic BP >135 mm Hg immediately after investigator witnessed intake of their antihypertensive morning drugs. Patients were asked to bring their prescribed medication to the clinical visit with one of the investigators (one of the authors of the article). Medication was documented and administered by the investigator and swallowed by the patient under continuous observation, to secure the intake of prescribed medication in prescribed doses. Patients were then continuously under the observation by the investigator to prohibit throwing up again of the pills until 24-hour ambulatory BP device had been mounted and tested out in a somewhat more lengthy procedure than usually to prolong the period of observation. Patients stayed in the hospital for 2 hours to capture those with potential symptomatic hypotension caused by full intake of medication. Visits with subsequent ambulatory BP measurements were done in the morning, and further observation of patients in the hospital was done during working hours.Plasma and urine metabolites of drugs were not measured because these tests would not have contributed in the present situation. Such tests could have identified the nondrug compliant patients but not secured their intake of medication. See Editorial Commentary, pp 450-452Abstract-It is unknown whether the decline in blood pressure (BP) after renal denervation (RDN) is caused by denervation itself or concomitantly improved drug adherence. We aimed to investigate the BP lowering effect of RDN in true treatmentresistant hypertension by excluding patients with poor drug adherence. Patients with resistant hypertension (n=18) were referred for a thorough clinical and laboratory work-up. Treat...

More Research Is Needed to Investigate the Effect of Denervation on Blood Pressure

“…A third reason may be because of the variation in the blood pressure response to renal denervation. The responder rates (a decrease in systolic blood pressure of ≥10 mm Hg) were only 33% and 50%, respectively, in the reports from Fadl Elmula et al 2 and Hart et al, 3 and these values were lower than those in the Symplicity HTN-1 study. These studies highlight that a big variation in the response of blood pressure to renal denervation exists, and that in some patients blood pressure may increase.…”

“…However, it did not cite other studies that did not observe a decrease in blood pressure after renal denervation. For example, Fadl Elmula et al 2 and Hart et al 3 separately reported that renal denervation did not decrease office systolic blood pressure. In addition, some studies, for example, the report of Witkowski et al, 4 showed that renal denervation did not decrease ambulatory blood pressure.…”

Renal sympatisk denervering ved terapiresistent hypertensjon

“…I Norge er det nylig startet en studie med renal denervering ved Universitetssykehuset Nord-Norge i Tromsø (17) og en annen ved Oslo universitetssykehus, Ullevål -«Oslo RDN Study» (NCT 01673516) (18). I Oslostudien randomiseres pasientene til renal denervering eller spesialtilpasset medikamentell behandling etter undersøkelse med impedanskardiografi (19).…”

“…Den første åpne fasen av Oslo RDN Study er publisert (18). Den viser usikker effekt på blodtrykket hos pasienter med dokumentert behandlingsresistent hypertensjon.…”

“…Det er publisert flere oversiktsartikler der det manes til forsiktighet, og det stilles en rekke kritiske spørsmål til dokumentasjon og ukritisk bruk av renal denervering (21,23,24). Fra et internasjonalt samarbeidsprosjekt, der studiene i Tromsø og Oslo inngår (17,18), er det nylig rapportert resultater fra 109 pasienter (25). Den blodtrykkssenkende effekten er langt mer beskjeden enn i Symplicity-1-og Symplicity-2-studiene (12,14).…”