Rebuttal from Jens Jordan

The new interventional treatments discussed in this CrossTalk debate address fundamental physiological mechanisms regulating autonomic nervous system activity and blood pressure, namely renal innervation, peripheral chemoreceptors, or carotid baroreflexes. The solid physiological rationale behind catheter-based renal denervation (Ratcliffe et al. 2014) and carotid chemoreceptor denervation/modulation (Schlaich et al. 2014) has been reviewed by a group of internationally recognized experts in the field. There is not much I could add. I would argue that catheter-based renal denervation, carotid chemoreceptor denervation/modulation and electrical carotid sinus stimulation deserved to undergo rigorous clinical testing. However, the road from a good idea to an effective treatment that can be incorporated into routine clinical care is a long one.

Both Ratcliffe et al. (2014) and Schlaich et al. (2014) suggest that silver bullet interventional cures are unlikely. I could not agree more. Interventional treatments for resistant primary hypertension may simply fail for technical reasons. The technology ought to be improved and we should find ways to identify technical failure early on. More importantly, there are pathophysiological reasons why not all patients will respond to a treatment lowering blood pressure through sole manipulation of sympathetic nervous system activity. The statement by Schlaich et al. (2014) that sympathetic activation is the hallmark of arterial hypertension is somewhat misleading. Instead, the contribution of sympathetic activity to arterial hypertension appears to vary from patient to patient. We applied pharmacological ganglionic blockade, which acutely abolishes sympathetic and parasympathetic efferent activity, to gauge autonomic nervous system contributions to primary hypertension in an earlier study (Jordan et al. 2002). In some patients, blood pressure remained elevated during ganglionic blockade. Similarly, in rare patients with near complete loss of peripheral autonomic nerves and supine hypertension, blood pressure remains elevated during ganglionic blockade (Shannon et al. 2000). Sympathetic inhibition cannot control blood pressure in all patients.

The column heading in the paper by Schlaich et al. stating that catheter-based renal denervation is safe and effective may be a little too optimistic. The fact that the procedure did not lower blood pressure in Simplicity-3 compared to rigorous controls cannot be neglected. In the past, European regulations permitted approval of devices in the absence of true efficacy data. The company producing a device had to show that operator and patient are not harmed and that the device serves its stated purpose. Data from smaller-scaled studies without a rigorous control group were sufficient for the agencies. Arterial stents served the stated purpose abolishing atherosclerotic renal artery stenosis. However, they failed miserably in controlling hypertension (Cooper et al. 2014). The scientific community should be smarter by now and not accept treatments that have not been proven useful in sufficiently large and well-controlled clinical trials. Finally, procedures should be tested with the same rigor as tablet-based interventions. Simplicity-3 (Bhatt et al. 2014) was exemplary in that regard.

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Additional information

Competing interests

None declared.

Funding

None declared.