Novel Approach to Resistant Hypertension Reported

SAN FRANCISCO—Patients with resistant hypertension may achieve significant and profound reductions in blood pressure (BP) with a single dose of intrathecal (IT) clonidine, according to new study presented at the 28th Annual Scientific Meeting of the American Society of Hypertension.

The study is the first to look at any intrathecal drug for refractory hypertension, said investigator Richard Rauck, MD, Clinical Associate Professor, Department of Anesthesiology, Wake Forest University Baptist Health, Winston Salem, N.C. “This will not be practical for patients who can get their blood pressure managed with a combination of oral medications.  However, it can be a very practical alternative when compared to other invasive methods for correcting refractory blood pressure.”

Oral clonidine has long been approved for treating hypertension, but it often produces significant adverse effects before adequate reductions in blood pressure are achieved. Currently, IT clonidine is commonly prescribed for implantable drug pumps to treat chronic pain. Studies suggest that it often lowers BP. Clonidine at the level of the spinal cord has been shown to activate alpha-2-adrenoceptors on the cell bodies of preganglionic sympathetic neurons and subsequently decreases sympathetic output.

In a prospective, single-arm, open-label trial, Dr. Rauck and his colleagues enrolled 10 patients with resistant hypertension, which was defined as blood pressure greater than 140/90 mm Hg at screening and on at least three antihypertensive medications, including a diuretic. The patients received a single 150-mcg bolus dose of lumbar IT clonidine. The patients stayed on their current oral hypertension medications during the study period. The researchers recorded BP at 10-minute intervals.

Following IT clonidine infusion, patients achieved significant reductions in both systolic blood pressure (from 155 to 98 mm Hg) and diastolic (88 to 57 mm Hg). The time to peak reduction in systolic pressure was achieved within 35 minutes of receiving the treatment. The decreases in systolic pressure were positively correlated with the magnitude of baseline levels.

“We were somewhat surprised at the consistent findings we saw in all patients treated,” Dr. Rauck told Renal & Urology News. “We knew intrathecal clonidine should be a powerful anti-hypertensive drug based on work in chronic pain, but I didn't know if it would be this robust in a refractory hypertensive group of patients.”

Six of the 10 patients experienced increases in sedation, and five experienced increases in dry mouth. No patient required vasopressor rescue therapy.

Although the findings are promising, placebo-controlled, dose-escalating studies are need to determine the long-term efficacy of IT clonidine infusion in patients with resistant hypertension.   

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