Renal denervation: Are we on the right path?

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When renal sympathetic denervation, an endovascular procedure designed to treat resistant hypertension, failed to meet its efficacy goal in the SYMPLICITY HTN-3 trial,1 the news was disappointing.

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In this issue of the Cleveland Clinic Journal of Medicine, Shishehbor et al2 provide a critical review of the findings of that trial and summarize its intricacies, as well as the results of other important trials of renal denervation therapy for hypertension. To their excellent observations, we would like to add some of our own.


The worldwide prevalence of hypertension is increasing. In the year 2000, about 26% of the adult world population had hypertension; by the year 2025, the number is projected to rise to 29%—1.56 billion people.3

Only about 50% of patients with hypertension are treated for it and, of those, about half have it adequately controlled. In one report, about 30% of US patients with hypertension had adequate blood pressure control.4

Patients who have uncontrolled hypertension are usually older and more obese, have higher baseline blood pressure and excessive salt intake, and are more likely to have chronic kidney disease, diabetes, obstructive sleep apnea, and aldosterone excess.5 Many of these conditions are also associated with increased sympathetic nervous system activity.6

Resistance and pseudoresistance

But lack of control of blood pressure is not the same as resistant hypertension. It is important to differentiate resistant hypertension from pseudoresistant hypertension, ie, hypertension that only seems to be resistant.7 Resistant hypertension affects 12.8% of all drug-treated hypertensive patients in the United States, according to data from the National Health and Nutrition Examination Survey.8

Factors that can cause pseudoresistant hypertension include:

Suboptimal antihypertensive regimens (truly resistant hypertension means blood pressure that remains high despite concurrent treatment with 3 antihypertensive drugs of different classes, 1 of which is a diuretic, in maximal doses)

The white coat effect (higher blood pressure in the office than at home, presumably due to the stress of an office visit)

  • Suboptimal blood pressure measurement techniques (eg, use of a cuff that is too small, causing falsely high readings)
  • Physician inertia (eg, failure to change a regimen that is not working)
  • Lifestyle factors (eg, excessive sodium intake)
  • Medications that interfere with blood pressure control (eg, nonsteroidal anti-inflammatory drugs)
  • Poor adherence to prescribed medications.

Causes of secondary hypertension such as obstructive sleep apnea, primary aldosteronism, and renal artery stenosis should also be ruled out before concluding that a patient has resistant hypertension.

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