Adherence to antihypertensive treatment (AHT) is usually assessed by scales such as Morisky Medication Adherence Scale questionnaires (MMAS-4, MMAS-8) but objective urinary drug levels quantification by liquid chromatography mass spectrometry (LC-MS/MS) is now available. Our aim was to compare adherence assessed by LC-MS/MS or (MMAS-4/ MMAS-8) in patients with resistant hypertension (RH), compared to patients with controlled hypertension (CH).

RH cohort consisted in 82 outpatients with daytime ABPM > 135/85mmHg after 4 weeks treatment with a standardised triple AHT: amlodipine + RAS blocker + thiazide. The CH cohort consisted in 91 patients followed in a routine care practice with controlled office BP (<140/90mmHg) by a median of 2 (range 1-4) AHT. Urinary drug levels of 14 AHT or their metabolites were evaluated by LC-MS/MS. MMAS-4 was only available in CH cohort and MMAS-8 only in RH cohort. Patients were aware (RH) or not (CH) of the measurement.

Full adherence was defined by the presence of all prescribed drugs, partial adherence by the absence of at least one drug and finally full non-adherence by the absence of all antihypertensive drugs

LC-MS/MS results: in the RH cohort, 63 patients (77%) were adherent, 11 (13%) were partly non-adherent and 8 (10%) were fully non-adherent. In the CH cohort, 86 (93%) were adherent, 5 (6%) were partly non-adherent, and 1 (1%) was fully non-adherent. Office SBP was significantly higher in non-adherent (partially or fully) than in fully adherent patients (median: 140 vs. 130mmHg, respectively; p=0.01). Office DBP did not differ. According to LCMS-MS, the full adherence rate was significantly higher in CH cohort compared to RH (p=0.002).

According to MMAS-8 available in 81 RH patients, 30 (37%) were fully adherent, and 51 (63%) were medium or low adherent. There was no concordance between LC-MS/MS and MMAS-8 in the same cohort (k=0.11, p=0.28). According to MMAS-4 available in 88 CH patients, 76 (86%) were fully adherent, and 12 (14%) were medium or low adherent and no significant difference in office SBP/DBP was observed between the two subgroups. There was no agreement between LCMS-MS and MMAS-4 (k=0.04, p=0.66).

In conclusion, measurement of urinary AHT by LC-MS/MS gives relevant information on adherence to treatment in patients attending an outpatient clinic. This information is not overlapping with questionnaires tests (MMAS). It confirms the role of objective non-adherence to treatment in resistance to treatment.