Antihypertensive Medication Adherence and Confirmation of True Refractory Hypertension

Refractory hypertension (RfHTN) is a phenotype of antihypertensive treatment failure defined as uncontrolled BP despite the use of effective doses of ≥5 antihypertensive medications including a long-acting thiazide-like diuretic (chlorthalidone) and a mineralocorticoid receptor antagonist (MRA). The degree of medication non-adherence is unknown among patients with RfHTN. In this prospective evaluation, 54 patients with apparent RfHTN were recruited from the University of Alabama at Birmingham Hypertension Clinic after having uncontrolled BP at three or more clinic visits. All patients’ BP was evaluated by automated office BP (AOBP) and 24-hr ambulatory BP monitoring (ABPM; n=49). Antihypertensive medication adherence was determined by measuring 24-hr urine specimens for antihypertensive medications and their metabolites by high-performance liquid chromatography-tandem mass spectrometry (n=45). Of the 45 patients who completed 24-hr ABPM, 40 (88.9%) had confirmed RfHTN based on an elevated AOBP (≥130/80 mmHg), mean 24-hour ABP (≥125/75 mmHg) and mean awake (day-time) ABP (≥130/80 mmHg).
Out of the 40 fully evaluated patients with RfHTN, 16 (40.0%) were fully adherent with all prescribed medications. Eighteen (45.0%) patients were partially adherent and 6 (15.0%) had none of the prescribed agents detected in their urine. Of 18 patients who were partially adherent, 5 (12.5%) were adherent with at least 5 medications, including
chlorthalidone and the MRA, consistent with true RfHTN.
Of patients identified as having apparent RfHTN, 52.5% were adherent with at least 5 antihypertensive medications, including chlorthalidone and a MRA, confirming true RfTHN. These findings validate RfHTN as a rare, but true phenotype of antihypertensive treatment failure.