Adherence to Antihypertensive Treatment and the Blood Pressure–Lowering Effects of Renal Denervation in the Renal Denervation for Hypertension (DENERHTN) Trial

Azizi, Michel; Pereira, Héléna; Hamdidouche, Idir; Gosse, Philippe; Monge, Matthieu; Bobrie, Guillaume; Delsart, Pascal; Mounier‐Véhier, Claire; Courand, Pierre‐Yves; Lantelme, Pierre; Denolle, Thierry; Dourmap-Collas, Caroline; Girerd, Xavier; Halimi, Jean Michel; Zannad, Faı̈ez; Ormezzano, Olivier; Vaı̈sse, B.; Herpin, D.; Ribstein, Jean; Chamontin, B.; Mourad, Jean‐Jacques; Ferrari, Émile; Plouin, Pierre‐François; Jullien, Vincent; Sapoval, Marc; Châtellier, Gilles; Amar, Laurence; Lorthioir, Aurélien; Pagny, Jean-Yves; Claisse, Guillaume; Midulla, Marco; Dauphin, R.; Fauvel, Jean‐Pierre; Rouvière, Olivier; Crémer, Antoine; Grenier, N.; Lebras, Y.; Trillaud, Hervé; Heautot, Jean-François; Larralde, A.; Paillard, F.; Cluzel, Philippe; Rosenbaum, David; Alison, D.; Claudon, M.; Popovic, Batric; Rossignol, Patrick; Baguet, Jean-Philippe; Thony, F.; Bartoli, Jean Michel; Drouineau, J; Sosner, P.; Tasu, JP; Velasco, Sonia; Vernhet-Kovacsik, H.; Bouhanick, Béatrice; Rousseau, Hervé; Jeune, Sylvain Le; Lopez‐Sublet, Marilucy; Bellmann, L.; Esnault, Vincent; Durand‐Zaleski, Isabelle; Bérégi, J.P.; Lièvre, Michel; Persu, Alexandre

doi:10.1161/circulationaha.116.022922

Cited by 137 publications

(78 citation statements)

References 34 publications

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“…There was, however, no detectible difference in blood pressure by adherence among patients prescribed fewer than three antihypertensive medications. While this is the first study to use a blood assay to measure antihypertensive adherence in an ED setting, patterns of adherence by number and class of prescribed antihypertensive medications and the relationship between adherence and SBP were similar to previous studies conducted in outpatient specialty clinics and among patients with resistant hypertension, 27–38 supporting the validity of our findings.…”

Section: Discussionsupporting

confidence: 86%

Systolic Blood Pressure and Biochemical Assessment of Adherence

et al. 2017

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Elevated blood pressure is common in the emergency department, but the relationship between antihypertensive medication adherence and blood pressure in the emergency department is unclear. This cross sectional study tested the hypothesis that higher antihypertensive adherence is associated with lower systolic blood pressure in the emergency department among adults with hypertension who sought emergency department care at an academic hospital from July 2012-April 2013. Biochemical assessment of antihypertensive adherence was performed using a mass spectrometry blood assay, and the primary outcome was average emergency department systolic blood pressure. Analyses were stratified by number of prescribed antihypertensives (<3, ≥3) and adjusted for age, sex, race, insurance, literacy, numeracy, education, body mass index, and co-morbidities. Among 85 patients prescribed ≥3 antihypertensives, mean systolic blood pressure for adherent patients was 134.4 mm Hg (+/− 26.1 mm Hg), and in adjusted analysis was −20.8 mmHg (95% CI −34.2 to −7.4 mm Hg, p=0.003) different from non-adherent patients. Among 176 patients prescribed <3 antihypertensives, mean SBP was 135.5 mm Hg (+/− 20.6 mm Hg) for adherent patients, with no difference by adherence in adjusted analysis (+2.9 mm Hg, 95% CI −4.7 to 10.5 mm Hg, p=0.45). Antihypertensive non-adherence identified by biochemical assessment was common and associated with higher systolic blood pressure in the emergency department among patients who had a primary care provider and health insurance and who were prescribed ≥3 antihypertensives. Biochemical assessment of antihypertensives could help distinguish medication non-adherence from other contributors to elevated blood pressure and identify target populations for intervention.

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Section: Discussionsupporting

confidence: 86%

Systolic Blood Pressure and Biochemical Assessment of Adherence

et al. 2017

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“…We have demonstrated that approximately one in three patients referred for renal denervation was non-adherent to their antihypertensive treatment [18•]. The recent data from DENERHTN trial suggest that non-adherence is even more common amongst patients in whom renal denervation was conducted [57]. Thus, it is worth considering screening for non-adherence in patients with resistant hypertension prior to irreversible and expensive interventions such as renal denervation.…”

Section: When To Assess For Non-adherencementioning

confidence: 99%

How to Screen for Non-Adherence to Antihypertensive Therapy

et al. 2016

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The quality of assessment of non-adherence to treatment in hypertensive is poor. Within this review, we discuss the different methods used to assess adherence to blood-pressure-lowering medications in hypertension patients. Subjective reports such as physicians’ perceptions are inaccurate, and questionnaires completed by patients tend to overreport adherence and show a low diagnostic specificity. Indirect objective methods such as pharmacy database records can be useful, but they are limited by the robustness of the recorded data. Electronic medication monitoring devices are accurate but usually track adherence to only a single medication and can be expensive. Overall, the fundamental issue with indirect objective measures is that they do not fully confirm ingestion of antihypertensive medications. Detection of antihypertensive medications in body fluids using liquid chromatography–tandem mass spectrometry is currently, in our view, the most robust and clinically useful method to assess non-adherence to blood-pressure-lowering treatment. It is particularly helpful in patients presenting with resistant, refractory or uncontrolled hypertension despite the optimal therapy. We recommend using this diagnostic strategy to detect non-adherence alongside a no-blame approach tailoring support to address the perceptions (e.g. beliefs about the illness and treatment) and practicalities (e.g. capability and resources) influencing motivation and ability to adhere.

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“…2 Overall, only ≈50% of patients were fully adherent in both groups. Although discouraging, the results are informative in confirming similar levels of drug exposure in both groups, excluding different levels of medication adherence as the cause of the BP difference between groups.…”

Section: Renal Nerve Denervation and Resistant Hypertensionmentioning

confidence: 93%

“…2 Exposure to ramipril was confirmed by measurement of the urine N-acetyl-seryl-aspartyl-lysyl-proline/creatinine ratio, and exposure to other medications was detected by measurement of the prescribed drug or its metabolites in urine or plasma samples by ultrahigh-performance liquid chromatography tandem mass spectrometry.…”

Section: Renal Nerve Denervation and Resistant Hypertensionmentioning

confidence: 99%

Renal Nerve Denervation, Adherence, and Management of Resistant Hypertension

Calhoun

2016

Circulation

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S ince publication of the SYMPLICITY HTN-3 trial (Renal Denervation in PatientsWith Uncontrolled Hypertension) results in 2014, which reported a similar blood pressure (BP) reduction in subjects with resistant hypertension who had either renal nerve denervation (RND) or sham intervention, there has been much discussion as to whether RND truly provides antihypertensive benefit.1 The discussion has included suggestions that RND functionally does very little, if anything, such that any associated BP reductions are placebo related; that observed benefit with RND is likely a consequence of a large regression to the mean effect in patients with high baseline BP values; and, in the case of SYMPLICITY HTN-3, inadequate nerve ablation by interventionalists inexperienced with the RND procedure resulting in reduced treatment benefit. There has also been concern that changes in medication adherence by patients participating in RND trials, in particular, immediately after having the procedure done or not, might be confounding the observed results. To explain the BP reductions in both the truly treated and sham-treated groups that occurred in SYMPLICITY HTN-3, one would have to suppose that the procedure had little effect and both patient groups were suddenly, but equally more adherent after randomization, such that the similar BP reductions were simply attributable to patients actually taking their medications; or, alternatively, that the procedure did have a true antihypertensive effect that was, however, obscured by increased medication adherence in the sham-treated patients. Because SYMPLICITY HTN-3 did not include biochemical assessment of medication adherence, such consideration has had to remain speculative.In this issue of Circulation, Azizi et al 2 provide important results relating to medication adherence and the true of effects of RND in a randomized trial format. They report no differences in drug exposure between patients with resistant hypertension participating in the DENERHTN (Renal Denervation for Hypertension) trial who had been randomly assigned either to RND with intensification of medical therapy versus intensification of medical therapy alone. The DENERHTN trial was a prospective, open-label, randomized evaluation of patients with uncontrolled resistant hypertension despite the use of a standardized regimen of indapamide, ramipril (or irbesartan), and amlodipine.3 True uncontrolled resistant hypertension was confirmed by ambulatory BP monitoring in all patients. Patients were randomly assigned to either RND with continued titration of antihypertensive medications as needed for uncontrolled BP or medication titration alone. The titration schedule was standardized and included, in order, the addition of spironolactone, bisoprolol, prazosin, and, last, rilmenidine. The primary end point was mean change in daytime systolic BP from baseline at 6 months follow-up as measured by ambulatory BP monitoring.Overall, 48 patients in the RND group and 53 control subjects completed the protocol and were included in the...

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Adherence to Antihypertensive Treatment and the Blood Pressure–Lowering Effects of Renal Denervation in the Renal Denervation for Hypertension (DENERHTN) Trial

Abstract: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01570777.

Cited by 137 publications

References 34 publications

Systolic Blood Pressure and Biochemical Assessment of Adherence

Systolic Blood Pressure and Biochemical Assessment of Adherence

How to Screen for Non-Adherence to Antihypertensive Therapy

Renal Nerve Denervation, Adherence, and Management of Resistant Hypertension

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