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Trial Lecture – time and place
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Adjudication committee
- First opponent: Professor Tine de Backer, Ghent University Hospital, Belgium
- Second opponent: Associate Professor Arif Elvan, Isala Hospitals, The Netherlands
- Third member and chair of the evaluation committee: Professor Torgeir Bruun Wyller, University of Oslo
Chair of the Defence
Professor Emeritus Ingebjørg Seljeflot, University of Oslo
Principal Supervisor
Fadl El Mula Mohamed Fadl El Mula, Oslo University Hospital
Summary
As many as 40% of hypertensive patients are unable to reach their blood pressure target despite treatment with antihypertensive drugs. Over the last years, medication non-adherence have emerged as one of the most important causes of treatment failure. Largely depending on the method used in this assessment, the prevalence of non-adherence ranges from <10% to as much as 86% throughout different studies. Traditionally, most assessment methods have been indirect, i.e. patient self-assessment based on questionnaires, or physician-assessment wherein a doctor guesses whether a patient is adherent or not. These methods have proven to be less accurate, whereas direct methods, such as detection of antihypertensive drugs- or metabolites in biological fluids present as more accurate methods of non-adherence assessment.
All 550 patients described in Paper I used ≥2 antihypertensive drugs and were referred/self-referred to a national hypertension study. They underwent thorough investigations including serum drug measurements of antihypertensive drugs. Furthermore, they were asked to complete a single, written question asking about their antihypertensive drug adherence. In addition, the physician assessed non-adherence based on a structured physician-patient interview.
The results showed a prevalence of non-adherence of 7.3% based on the direct method. The indirect methods poorly overlapped and only two patients were identified as non-adherent by all three methods. A higher number of prescribed daily pills-, a higher number of prescribed antihypertensive pills-, and less prescription of combination pills were associated with non-adherence. Further, a lower patient age and non-caucasian ethnicity were associated with non-adherence.
In the late 2000’s, renal denervation (RDN) was introduced as a potential treatment method for hypertension by introducing a catheter to the renal arteries and applying radiofrequency energy to ablate the sympathetic nerves within the adventitia of the artery wall. After the promising results from the first few studies, later randomized studied have shown the effect of RDN to be approximately equivalent to that of one antihypertensive drug. Although it is beyond doubt that RDN is able to reduce blood pressure, some patients seem to have a larger effect than others. Thus, it is important to find objective methods to identify these patients in advance. Additionally, long-term follow-up of patients who have undergone RDN is of importance to assess the safety- and efficacy of the procedure.
The patients in Papers II and III were specifically referred to a renal denervation study, suspected of having treatment-resistant hypertension, i.e. using maximally tolerable doses of at least 3 antihypertensive drugs of which one had to be a diuretic. After witnessed intake of their prescribed drugs, patients underwent office- and ambulatory blood pressure measurements. Patients who remained hypertensive on the 24h ambulatory measurement were randomized to either RDN or drug adjustment assisted by hemodynamic monitoring.
Paper II describes patients on long-term follow-up after three- and seven years. The two groups have similar blood pressure measurements on both visits, without any functional- or anatomical deterioration in renal function or any adverse events that could be attributed to the procedure.
Paper III describes heart rate variability- and continuous blood pressure measurements during stress tests along with simultaneous sampling of catecholamines during an orthostatic stress test and a cold-pressor test. Before randomization, the two groups were similar in heart rate variability, continuous blood pressure measurements and catecholamine assessment, whereas at six months follow up the RDN group had a significantly lower adrenaline concentration immediately following the cold-pressor test. Thus, RDN seems to be able to reduce adrenaline reactivity.
Additional information
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