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. 2021 May 10:12:668843.
doi: 10.3389/fphar.2021.668843. eCollection 2021.

Assessment of Anti-Hypertensive Drug Adherence by Serial Aldosterone-To-Renin Ratio Measurement

Fabrizio Buffolo  1 , Elisa Sconfienza  1 , Jacopo Burrello  1 , Isabel Losano  1 , Giulio Mengozzi  2 , Gabriella Priolo  2 , Valeria Avataneo  3 , Antonio D'Avolio  3 , Franco Veglio  1 , Franco Rabbia  1 , Paolo Mulatero  1 , Silvia Monticone  1
Affiliations

Assessment of Anti-Hypertensive Drug Adherence by Serial Aldosterone-To-Renin Ratio Measurement

Fabrizio Buffolo et al. Front Pharmacol. .

Abstract

Reduced or absent compliance to anti-hypertensive treatment is a major obstacle to the achievement of blood pressure target in patients with arterial hypertension. Current available methods for therapeutic adherence assessment display low accuracy, limited applicability in clinical practice and/or high costs. We designed a prospective study to evaluate the accuracy of serial measurement of ARR to assess the therapeutic compliance to RAAS inhibitors. We prospectively enrolled 80 subjects: 40 patients with arterial hypertension and 40 normotensive controls. The ARR was evaluated at baseline and 2 and 8 week after initiation of a RAAS inhibitor in patients with hypertension, and at baseline and 2 weeks for the control group. Adherence to the prescribed therapy was confirmed by therapeutic drug monitoring. We observed a significant increase of renin levels and reduction of aldosterone levels after RAAS inhibitors initiation, with consequent reduction of ARR. Delta ARR (ΔARR), defined as relative change in ARR before and after treatment initiation, provided high accuracy for determination of therapeutic compliance, with an AUC of 0.900 at 2 weeks and 0.886 at 8 weeks. A cut-off of -48% of ΔARR provided 90% sensitivity and 75% specificity, at 2 and 8 weeks. In conclusion, the measurement of ΔARR is a powerful test, cheap and widely available to accurately identify the non-adherence to RAAS inhibitors treatment. Herein we propose the implementation of ΔARR in clinical practice through a multi-step flow-chart for the management of patients with uncontrolled blood pressure, with identification of those suspected of non-adherence, reserving therapeutic drug monitoring for non-adherence confirmation.

Keywords: aldosterone; angiotensin receptor blocker; angiotensin-converting enzyme inhibitor; anti-hypertensive treatment; drug adherence; renin; therapeutic drug monitoring.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flow-chart of recruitment, treatment and follow-up of patients with hypertension and controls. ARB, angiotensin receptor blocker; ACEi, angiotensin converting enzyme inhibitor.
FIGURE 2
FIGURE 2
Hormonal changes at follow-up visits of patients with hypertension and controls. Scatter dot plots are showed with median (central line) and 25th–75th interquartile range (extremities). For patients treated with RAAS inhibitors relative changes of renin (A), aldosterone (B) and ARR (C) are showed in the upper part of the Figure. For healthy controls, relative changes of renin (C), aldosterone (D) and ARR (E) are showed in the lower part of the Figure. RAAS, renin-angiotensin-aldosterone system; ARR, aldosterone-to-renin ratio.
FIGURE 3
FIGURE 3
ROC curves of ΔARR for prediction of non-adherence to treatment with RAAS inhibitors. ROC, receiver operating characteristic; ΔARR, delta aldosterone-to-renin ratio; RAAS, renin-angiotensin-aldosterone system.
FIGURE 4
FIGURE 4
Flow-chart proposal for the management of patients with arterial hypertension. PA, primary aldosteronism; ARB, angiotensin receptor blocker; ACEi, angiotensin converting enzyme inhibitor; ΔARR, delta aldosterone-to-renin ratio.
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