J. Menne

Interventionelle Strategien zur Behandlung der Hypertonie

A number of invasive treatment approaches have become established in the management of severe treatment-resistant hypertension in recent years, including renal denervation and baroreceptor activation therapy. Both methods achieve their antihypertensive effect by influencing the autonomic nervous system. Renal denervation in particular has stimulated considerable interest, since it is simple to perform and initial studies have yielded highly promising results. However, enthusiasm has waned significantly since the initial euphoria. This is due to the fact that the first randomized placebo-controlled double-blind study showed the method to have no significant effect on blood pressure. This experience illustrates the importance of conducting double-blind studies. On the other hand, these results should not lead to renal denervation being shelved. On the contrary, it is worth attempting to improve the treatment and develop criteria to identify which patients it is likely to benefit. Although experience with baroreceptor activation therapy is significantly more limited, similar conclusions can be drawn on it, despite the fact that-in contrast to renal denervation-it achieved a blood pressure reduction of around 10 mmHg in a double-blind study. A potential novel treatment approach lies in creating an arteriovenous shunt between the iliac artery and vein, which has a particularly marked effect on diastolic blood pressure by reducing peripheral resistance. Therapy using brain stimulation of areas in the brainstem region responsible for blood pressure regulation is still at an experimental stage.

Renale Denervierung und Hypertonie

ZusammenfassungWenig neue Methoden der antihypertensiven Therapie haben in den letzten Jahren zu so viel Diskussion geführt wie die sog. renale Denervierung der sympathischen Nervenfasern. Die Stimulation des Sympathikus beeinflusst die Funktion der Niere durch die Freisetzung von Renin, eine gesteigerte Aufnahme von NaCl und durch Vasokonstriktion der renalen Widerstandsgefäße. Diese Mechanismen steigern den Blutdruck und sollen durch die Ablation der Nervenfasern blockiert werden. Die Entwicklung einer sicheren Ablationsmethode beim Menschen in den letzten Jahren hat dieses Verfahren klinisch einsetzbar gemacht. In den ersten klinischen Studien hat dieses Verfahren beeindruckende Blutdruckabfälle gezeigt. Diese therapeutische Wirksamkeit war in diesen Studien auch noch nach Jahren nachweisbar. Darüber hinaus konnten positive Wirkungen auf andere, durch den Sympathikus verursachte, Probleme wie den Glukosemetabolismus und die Schlafapnoe nachgewiesen werden. Allerdings zeigten sich bereits in den ersten kontrollierten Untersuchungen teilweise „therapieresistente“ Patienten. In der ersten großen randomisierten, doppelblind durchgeführten Studie (Simplicity-3) konnte keine therapeutische Wirkung der Nervenablation auf den Blutdruck nachgewiesen werden. Dem stehen Registerdaten und unkontrollierte Befunde mit einer sehr ausgeprägten therapeutischen Wirksamkeit entgegen. Erklärungen für den negativen Ausgang von Simplicity-3 sind vielfältig und reichen von Compliance bis zum Versagen der Methode in dieser Studie. Es wird notwendig sein, die „ansprechbaren“ Patienten zu definieren, diese mit geeigneten diagnostischen Methoden zu charakterisieren und diese dann in kontrollierte Studien einzuschleusen. Bis dahin hat das Verfahren der renalen Ablation einen experimentellen Charakter.AbstractCatheter-based renal nerve ablation can lower blood pressure (BP) in hypertensive patients. The concept is based on solid physiological studies suggesting that efferent and afferent renal nerves contribute to arterial hypertension. The preliminary results on the efficacy and safety of catheter-based renal nerve ablation on BP control in resistant hypertension have been encouraging; however, these studies were uncontrolled. In several small studies it was observed early that most patients can be controlled by pharmaceutical treatment and only a few patients respond to ablation therapy. A large prospective trial with a control group (sham treatment) was therefore necessary. The Simplicity-3 trial fulfilled these criteria. More than 600 patients were successfully studied and in March 2014 the results were published. No significant differences between the two groups were observed, one treated with renal nerve ablation and the other group controlled only by medication. These results are in contrast to the previous (uncontrolled) studies and observations from a worldwide registry. Several explanations have been put forward to explain these results. Important are (1) compliance, i.e. patients taking their medication during the study and also (2) inexperience with the method in small centers. Simplicity-3 has put a halt on using renal denervation in most countries. It is now important to find out why the method only works in some patients, what the criteria to use it are and to define a patient group where renal denervation is useful as a therapeutic method to treat patients with hypertension.