Full results of the SYMPLICITY HTN-3 trial presented at the American College of Cardiology 2014 Scientific Sessions underscored what the many physicians had feared: that renal denervation may not be a panacea for resistant hypertension after all.

Hopes were dashed when the principal investigators announced that after six months, the mean reduction in systolic blood in patients randomized to the renal denervation arm was only 2.39 mmHg lower than in those randomized to the sham arm—a difference that was not statistically significant.

The change in 24-hour ambulatory blood pressure at six months was equally minimal, with an insignificant difference of 1.96 mmHg in favor of the procedure arm.

A conundrum

Renal hypertension is approved in more than 80 countries, with an estimated 10,000 procedures performed to date.  Multiple studies published in leading journals have shown renal denervation can produce reductions in systolic blood pressure as great as 30 to 40 mm Hg. Patients enrolled in SYMPLICITY HTN-3 achieved half that reduction. While such large drops are considered a favorable response in patients with a systolic pressure greater than 160 mmHg, the blood pressure in patients who were not treated fell nearly as much.

Three possible explanations have been proposed. One is that the participants in the sham arm became more diligent than usual in taking their antihypertension medications when closely watched. Two, renal denervation was not accomplished in all patients. Three, blood pressure responds better when patients are left on their medical regimen for long periods of time, rather than changing regimens more often in hopes of finding a more effective combination or dose of medications.

Medtronic is convinced renal denervation has value and intends to continue investigating possible explanations for why the procedure was largely ineffective in the SYMPLICITY HTN-3 cohort.