Impact of Medication Adherence on the Effect of Renal Denervation: The SYMPATHY Trial

Abstract

Randomized trials of catheter-based renal denervation (RDN) as therapy for resistant hypertension showed conflicting results in blood pressure (BP) lowering effect. Adherence to medication is modest in this patient group and may importantly drive these conflicting results. SYMPATHY is a prospective open label multicenter trial in Dutch patients with resistant hypertension. Primary outcome was change in daytime systolic ambulatory BP at 6 months. Patients were randomly assigned to RDN on top of usual care. Adherence to BP lowering drugs was assessed at baseline and follow-up, using blood samples drawn synchronously with BP measurements. Patients and physicians were unaware of the adherence assessment. Primary analyses showed a mean difference between RDN (n=95) and control (n=44) in changes in daytime systolic ambulatory BP after 6 months of 2.0 mm Hg (95% confidence interval, -6.1 to 10.2 mm Hg) in favor of control. In 80% of patients, fewer medications were detected than prescribed and adherence changed during follow-up in 31%. In those with stable adherence during follow-up, mean difference between RDN and control for daytime systolic ambulatory BP was -3.3 mm Hg (-13.7 to 7.2 mm Hg) in favor of RDN. RDN as therapy for resistant hypertension was not superior to usual care. Objective assessment of medication use shows that medication adherence is extremely poor, when patients are unaware of monitoring. Changes over time in adherence are common and affect treatment estimates considerably. Objective measurement of medication adherence during follow-up is strongly recommended in randomized trials.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01850901.

Keywords: blood pressure; meta-analysis; randomized controlled trial; renal denervation; sympathetic nervous system.