Resistant hypertension? Assessment of adherence by toxicological urine analysis

Jung, Ok‐Sang; Gechter, Janis L.; Wunder, Cora; Paulke, Alexander; Bartel, Christine; Geiger, Helmut; Toennes, Stefan W.

doi:10.1097/hjh.0b013e32835e2286

Cited by 429 publications

(317 citation statements)

References 43 publications

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“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

“…Triggered by 2 recent publications on nonadherence to antihypertensive treatment, as assessed by toxicological analysis,14, 15 we analyzed adherence rates in patients with TRH at baseline and at 6 months after renal denervation. The study included only those patients who successfully completed their 6‐month follow‐up period 20, 21.…”

Section: Introductionmentioning

confidence: 99%

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

Schmieder

Ott

Schmid

et al. 2016

JAHA

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BackgroundAdherence to medication has been repeatedly proposed to represent a major cause of treatment‐resistant hypertension (TRH); however, treatment decisions such as treating TRH with renal denervation depend on accurate judgment of adherence. We carefully analyzed adherence rates to medication before and after renal denervation and its effect on blood pressure (BP) control.Methods and ResultsEighty patients with TRH were included in 2 prospective observational studies that assessed the difference of potential antihypertensive and nephroprotective effects of renal denervation. To compare prescribed with actual medication intake (representing a measure of adherence), we analyzed urine samples collected at baseline and at 6 months after renal denervation for antihypertensive compounds or metabolites (by liquid chromatography–mass spectrometry). In addition to office BP, 24‐hour ambulatory BP and central hemodynamics (central systolic pressure, central pulse pressure) were assessed. Informed consent for analyses of urine metabolites was obtained from 79 of 80 patients. Actual intake of all antihypertensive drugs was detected at baseline and at 6 months after renal denervation in 44 (56%) and 52 (66%) patients, respectively; 1 drug was missing in 22 (28%) and 17 (22%) patients, respectively, and ≥2 drugs were missing in 13 (16%) and 10 (13%) patients, respectively. At baseline, 24‐hour ambulatory BP (P=0.049) and central systolic BP (P=0.012) were higher in nonadherent patients. Adherence did not significantly change overall (McNemar‐Bowker test, P=0.362). An increase in adherence was observed in 21 patients, and a decrease was observed in 11 patients. The decrease in 24‐hour ambulatory BP was not different in those with stable adherence 6 months after renal denervation (n=41, −7±13 mm Hg) compared with those with increased adherence (n=21, −10±13 mm Hg) and decreased adherence (n=11, −7±14 mm Hg) (P>0.20). Our study is limited by the relatively small sample size and potentially by the specific health environment of our university center (Northern Bavaria, Germany).ConclusionsNonadherence to medication among patients with TRH was relatively low: ≈1 of 6 patients with TRH did not take ≥2 of the prescribed drugs. Adherence pattern did not change significantly after renal denervation and had no impact on the overall observed BP changes, supporting the concept that renal denervation is an effective treatment in patients with TRH.Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifiers: NCT00888433, NCT01442883 and NCT01687725.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Schmieder

Ott

Schmid

et al. 2016

JAHA

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“…1 Recent studies from our group and others have reported a high prevalence of non-adherence to antihypertensive medications among patients with a-TRH (50-60%) using the highly sensitive technique of therapeutic drug monitoring. [2][3][4][5] Despite the enormous burden of non-adherence to the health care system, practical and reliable methods of adherence detection are not well developed. Adherence can be monitored by several methods such as patient self-report, detailed questionnaire, pill counts, prescription fill rate, or electronic pillboxes.…”

Section: Introductionmentioning

confidence: 99%

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

Pandey

Raza

Velasco

et al. 2015

Journal of the American Society of Hypertension

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The Morisky Medication Adherence Scale (MMAS-8) is a questionnaire developed for screening of non-adherence in patients with several chronic conditions, including uncomplicated hypertension. However, its accuracy in predicting nonadherence in patients with apparent treatment-resistant hypertension (a-TRH) is not known. Accordingly, we performed a retrospective study in 47 patients with a-TRH who had completed the eight-item MMAS during the initial clinic visit. Non-adherence was defined as presence of undetected serum levels of at least one prescribed antihypertensive drug by therapeutic drug monitoring. We found that 26% of patients were considered to have low adherence score (<6), while the actual prevalence of non-adherence was 51% by therapeutic drug monitoring. Sensitivity of the MMAS-8 was 26% (95% confidence interval, 10.3%-48.4%) with specificity of 75% (95% confidence interval, 53.3%-90.2%). By multivariate analysis, the MMAS-8 score was not an independent predictor of non-adherence, while certain clinical parameters such as heart rate were found to be independent predictors of non-adherence. Our study suggested limited accuracy of the MMAS-8 in detecting medication non-adherence in a-TRH. J Am Soc Hypertens 2015;9(6):420-426.

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“…A secondary form of hypertension is often present in treatment-resistant hypertension. Therefore, in the case of insufficient response to treatment with medication, office or white coat hypertension (pseudoresistance) [8,9], unreliable intake of medication [10,11], suboptimal or false medication combination, and secondary types of hypertension must be ruled out as the cause of "treatment-resistant" hypertension.…”

Section: Clinical Practicementioning

confidence: 99%

Renal Denervation: Unde Venis et Quo Vadis?

Nähle

Düsing²,

Schild

2015

Fortschr Röntgenstr

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!Objective and Methods: Renal denervation is a minimally invasive, catheter-based option for the treatment of refractory hypertension. Indications and contraindications for renal denervation have been defined in an interdisciplinary manner. The efficacy and safety of the procedure were evaluated. Results: Currently, indication for renal denervation is limited to patients with primary hypertension and a systolic blood pressure of ≥ 160 mm Hg (or ≥ 150 mm Hg in diabetes type 2) despite optimal medical therapy with ≥ 3 different antihypertensive drugs. In this specific patient population, an average blood pressure reduction of 32/14 mmHg was observed in non-randomized/-controlled trials after renal denervation. These results were not confirmed in the first randomized controlled trial with a non-significantly superior blood pressure reduction of 14.1 ± 23.9 mm Hg compared to controls (−11.74 ± 25.94 mm Hg, difference −2.39 mm Hg p = 0.26 for superiority with a margin of 5 mm Hg) who underwent a sham procedure. Conclusion: The efficacy and long-term effects of renal denervation need to be re-evaluated in light of the HTN3 study results. To date, renal denervation should not be performed outside of clinical trials. Future trials should also assess if renal denervation can be performed with sufficient safety and efficacy in patients with hypertension-associated diseases. The use of renal denervation as an alternative therapy (e. g. in patients with drug intolerance) can currently not be advocated. Key points:▶ The indication for renal denervation should be assessed in an interdisciplinary fashion and according to current guidelines with a special focus on ruling out secondary causes for arterial hypertension.▶ 5 -10 % of patients with hypertension suffer from refractory hypertension, but only about 1 % of patients meet the criteria for a renal denervation.▶ Renal denervation leads to a significant decrease in office blood pressure; however, the impact on 24-hour blood pressure measurements remains unclear.▶ In the first randomized controlled trial on renal denervation with a control group undergoing a sham procedure, blood pressure reduction failed to reach the anticipated level of superiority over best medical treatment.▶ Periprocedural complications are rare, but long-term safety can currently not be appraised due to the limited data available. Review 237Nähle CP et al.

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Resistant hypertension? Assessment of adherence by toxicological urine analysis

Cited by 429 publications

References 43 publications

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

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

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

Renal Denervation: Unde Venis et Quo Vadis?

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