Difficult-to-control arterial hypertension or uncooperative patients? The assessment of serum antihypertensive drug levels to differentiate non-responsiveness from non-adherence to recommended therapy

Abstract

Difficult-to-control arterial hypertension is a common medical problem that may result from severe hypertensive disease or from poor adherence to the recommended medical treatment. The identification of non-adherent patients is challenging, especially when non-adherence is intentional. The current report describes the use of serum levels of prescribed antihypertensive drugs to evaluate the adherence in individuals with difficult-to-control arterial hypertension. Serum drug levels (SDLs) were evaluated by liquid chromatography with mass spectrometry. The chromatographic separation was performed on a reversed-phase column with a gradient flow of the mobile phase. The detection of analyzed substances was accomplished on a linear ion-trap mass spectrometer. The subjects were labeled as non-adherent when the serum level of at least one of the evaluated drugs was below the limit of quantification. The study used data from 84 patients with arterial hypertension who underwent SDL assessment to verify compliance with the recommended treatment. Patients who presented with uncontrolled blood pressure despite the recommended combination of at least three antihypertensives were enrolled in the analysis. Based on the evaluation of the SDLs, all of the evaluated drugs were found in the sera of 29 (34.5%) of the study patients. In the remaining 55 (65.5%) patients, non-adherence was diagnosed. None of the prescribed antihypertensive drugs was detected in the sera of the 29 (34.5%) patients. Our data suggest that an assessment of SDLs might be helpful before an extensive evaluation is initiated for difficult-to-control hypertension.

Comparison of Morisky Medication Adherence Scale with therapeutic drug monitoring in apparent treatment–resistant hypertension

“…Although small sample size may be responsible for attenuation in the relationship, our study indicated elevated HR was a strong independent predictor of medication non-adherence, which was previously demonstrated in studies using therapeutic drug monitoring in a-TRH. 3,12 Presence of CKD, however, was found to be a predictor of adherence to treatment. It is unlikely that presence of CKD is directly responsible for the adherent behaviour, but older age and higher proportion of male in the adherent group may contribute to differences in the prevalence of CKD.…”

“…This technique has been validated previously for measuring levels of antihypertensive medications. 12,13 Non-adherence was defined as presence of serum levels below detection limit of at least one antihypertensive medication prescribed to the patient by therapeutic drug monitoring.…”

Adherence to Antihypertensive Medication in Treatment‐Resistant Hypertension Undergoing Renal Denervation

“…In all of these studies carried out in TRH or hypertensive patients with insufficient BP control, LC‐MS/MS was used to measure the drug levels, allowing a comparison of adherence rates. The definition of partial nonadherence, however, varies widely from “at least one or more substances missing” to “fewer than prescribed” or is not described in detail at all 14, 15, 16, 17. In our study, we used only 1 antihypertensive substances missing for the definition of partial adherence.…”

“…Electronic methods of adherence monitoring (ie, computerized records of pharmacy prescription or electronic monitoring of pill box opening) may be considered reliable alternatives, but it remains subject to the patient's behavior whether the removed pills are indeed ingested 1, 12, 13. Recently, toxicological urine analysis of the compounds or their metabolites has gained increasing interest 14, 15, 16, 17. These biochemical analyses represent spot assessments of adherence but are subject to the “white coat adherence” effect 18, 19.…”

Apparent resistant hypertension and medication adherence

“…The authors concluded that the assessment of serum drug levels might be helpful before an extensive evaluation is initiated for difficult-to-control hypertension. 5 Some limitations of the study require comment. It is unclear why only 84 of the 584 patients screened were eligible for reporting, which suggests the possibility of a large selection bias.…”