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

Roland E Schmieder, Christian Ott, Axel Schmid, Stefanie Friedrich, Iris Kistner, Tilmann Ditting, Roland Veelken, Michael Uder, Stefan W Toennes, Roland E Schmieder, Christian Ott, Axel Schmid, Stefanie Friedrich, Iris Kistner, Tilmann Ditting, Roland Veelken, Michael Uder, Stefan W Toennes

Abstract

Background: Adherence 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 results: Eighty 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).

Conclusions: Nonadherence 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.

Keywords: adherence; antihypertensive medication; renal denervation; resistant hypertension; treatment.

© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Figures

Figure 1
Figure 1
Adherence to therapy in different drug classes at baseline and 6‐month visits (descriptive illustration of percentages). ACEi indicates angiotensin‐converting enzyme inhibitor; ARB, angiotensin receptor blocker; Central, Central sympatholytic agent; CCB, calcium channel blocker.
Figure 2
Figure 2
Shift analysis of adherence pattern from baseline to 6‐month visit in patients with complete adherence (A), partial adherence (B), and nonadherence (C) at baseline (based on numeric definition). Med indicates medication.
Figure 3
Figure 3
A, Distribution of adherence level at baseline according to the percentage of medication detected. B, Shift analysis of adherence pattern from baseline to 6‐month visit (based on percentage definition).
Figure 4
Figure 4
Office BP (A and B) and 24‐hour ABP (C and D) at baseline categorized according to the adherence level (numeric [left] and percentage [right] definitions), mean±SEM. ABP indicates ambulatory blood pressure; BP, blood pressure; h, hour; SBP, systolic blood pressure.
Figure 5
Figure 5
Decrease in office BP (A) and 24‐hour ABP (B) after renal denervation in all study patients (N=79) and subgroups (stable adherence, increase in adherence, and decrease in adherence at 6 months) based on numeric definition, mean±SEM. ABP indicates ambulatory blood pressure; BP, blood pressure; h, hour; SBP, systolic blood pressure.
Figure 6
Figure 6
Decrease in office BP (A) and 24‐hour ABP (B) after renal denervation in all study patients (N=79) and subgroups (stable adherence, increase in adherence and decrease in adherence at 6 months) divided by whether ≥80% or <80% of the detectable drugs were detected (percentage definition), mean±SEM. ABP indicates ambulatory blood pressure; BP, blood pressure; SBP, systolic blood pressure.

References

    1. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353:487–497.
    1. Hill MN, Miller NH, Degeest S; American Society of Hypertension Writing G , Materson BJ, Black HR, Izzo JL Jr, Oparil S, Weber MA. Adherence and persistence with taking medication to control high blood pressure. J Am Soc Hypertens. 2011;5:56–63.
    1. Burnier M. Managing ‘resistance’: is adherence a target for treatment? Curr Opin Nephrol Hypertens. 2014;23:439–443.
    1. Mancia G, Zambon A, Soranna D, Merlino L, Corrao G. Factors involved in the discontinuation of antihypertensive drug therapy: an analysis from real life data. J Hypertens. 2014;32:1708–1715; discussion 1716.
    1. Corrao G, Parodi A, Nicotra F, Zambon A, Merlino L, Cesana G, Mancia G. Better compliance to antihypertensive medications reduces cardiovascular risk. J Hypertens. 2011;29:610–618.
    1. Mazzaglia G, Ambrosioni E, Alacqua M, Filippi A, Sessa E, Immordino V, Borghi C, Brignoli O, Caputi AP, Cricelli C, Mantovani LG. Adherence to antihypertensive medications and cardiovascular morbidity among newly diagnosed hypertensive patients. Circulation. 2009;120:1598–1605.
    1. Mathes J, Kostev K, Gabriel A, Pirk O, Schmieder RE. Relation of the first hypertension‐associated event with medication, compliance and persistence in naive hypertensive patients after initiating monotherapy. Int J Clin Pharmacol Ther. 2010;48:173–183.
    1. Mancia G, Parodi A, Merlino L, Corrao G. Heterogeneity in antihypertensive treatment discontinuation between drugs belonging to the same class. J Hypertens. 2011;29:1012–1018.
    1. Kronish IM, Woodward M, Sergie Z, Ogedegbe G, Falzon L, Mann DM. Meta‐analysis: impact of drug class on adherence to antihypertensives. Circulation. 2011;123:1611–1621.
    1. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, Christiaens T, Cifkova R, De Backer G, Dominiczak A, Galderisi M, Grobbee DE, Jaarsma T, Kirchhof P, Kjeldsen SE, Laurent S, Manolis AJ, Nilsson PM, Ruilope LM, Schmieder RE, Sirnes PA, Sleight P, Viigimaa M, Waeber B, Zannad F; Task Force M . 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013;31:1281–1357.
    1. De Geest S, Ruppar T, Berben L, Schonfeld S, Hill MN. Medication non‐adherence as a critical factor in the management of presumed resistant hypertension: a narrative review. EuroIntervention. 2014;9:1102–1109.
    1. Vrijens B, Vincze G, Kristanto P, Urquhart J, Burnier M. Adherence to prescribed antihypertensive drug treatments: longitudinal study of electronically compiled dosing histories. BMJ. 2008;336:1114–1117.
    1. Burnier M, Schneider MP, Chiolero A, Stubi CL, Brunner HR. Electronic compliance monitoring in resistant hypertension: the basis for rational therapeutic decisions. J Hypertens. 2001;19:335–341.
    1. Jung O, Gechter JL, Wunder C, Paulke A, Bartel C, Geiger H, Toennes SW. Resistant hypertension? Assessment of adherence by toxicological urine analysis. J Hypertens. 2013;31:766–774.
    1. Tomaszewski M, White C, Patel P, Masca N, Damani R, Hepworth J, Samani NJ, Gupta P, Madira W, Stanley A, Williams B. High rates of non‐adherence to antihypertensive treatment revealed by high‐performance liquid chromatography‐tandem mass spectrometry (HP LC‐MS/MS) urine analysis. Heart. 2014;100:855–861.
    1. Strauch B, Petrak O, Zelinka T, Rosa J, Somloova Z, Indra T, Chytil L, Maresova V, Kurcova I, Holaj R, Wichterle D, Widimsky J Jr. Precise assessment of noncompliance with the antihypertensive therapy in patients with resistant hypertension using toxicological serum analysis. J Hypertens. 2013;31:2455–2461.
    1. Ceral J, Habrdova V, Vorisek V, Bima M, Pelouch R, Solar M. 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. Hypertens Res. 2011;34:87–90.
    1. Feinstein AR. On white‐coat effects and the electronic monitoring of compliance. Arch Intern Med. 1990;150:1377–1378.
    1. Cramer JA, Scheyer RD, Mattson RH. Compliance declines between clinic visits. Arch Intern Med. 1990;150:1509–1510.
    1. Ott C, Mahfoud F, Schmid A, Ditting T, Veelken R, Ewen S, Ukena C, Uder M, Bohm M, Schmieder RE. Improvement of albuminuria after renal denervation. Int J Cardiol. 2014;173:311–315.
    1. Ott C, Mahfoud F, Schmid A, Ditting T, Sobotka PA, Veelken R, Spies A, Ukena C, Laufs U, Uder M, Bohm M, Schmieder RE. Renal denervation in moderate treatment‐resistant hypertension. J Am Coll Cardiol. 2013;62:1880–1886.
    1. Ott C, Mahfoud F, Schmid A, Toennes SW, Ewen S, Ditting T, Veelken R, Ukena C, Uder M, Bohm M, Schmieder RE. Renal denervation preserves renal function in patients with chronic kidney disease and resistant hypertension. J Hypertens. 2015;33:1261–1266.
    1. Ott C, Schmid A, Toennes SW, Ditting T, Veelken R, Uder M, Schmieder RE. Central pulse pressure predicts BP reduction after renal denervation in patients with treatment‐resistant hypertension. EuroIntervention. 2015;11:110–116.
    1. Schmieder RE, Redon J, Grassi G, Kjeldsen SE, Mancia G, Narkiewicz K, Parati G, Ruilope L, van de Borne P, Tsioufis C. ESH position paper: renal denervation—an interventional therapy of resistant hypertension. J Hypertens. 2012;30:837–841.
    1. Mahfoud F, Luscher TF, Andersson B, Baumgartner I, Cifkova R, Dimario C, Doevendans P, Fagard R, Fajadet J, Komajda M, Lefevre T, Lotan C, Sievert H, Volpe M, Widimsky P, Wijns W, Williams B, Windecker S, Witkowski A, Zeller T, Bohm M; European Society of C . Expert consensus document from the European Society of Cardiology on catheter‐based renal denervation. Eur Heart J. 2013;34:2149–2157.
    1. Parati G, Stergiou G, O'Brien E, Asmar R, Beilin L, Bilo G, Clement D, de la Sierra A, de Leeuw P, Dolan E, Fagard R, Graves J, Head GA, Imai Y, Kario K, Lurbe E, Mallion JM, Mancia G, Mengden T, Myers M, Ogedegbe G, Ohkubo T, Omboni S, Palatini P, Redon J, Ruilope LM, Shennan A, Staessen JA, vanMontfrans G, Verdecchia P, Waeber B, Wang J, Zanchetti A, Zhang Y. European society of hypertension practice guidelines for ambulatory blood pressure monitoring. J Hypertens. 2014;32:1359–1366.
    1. Ott C, Raff U, Harazny JM, Michelson G, Schmieder RE. Central pulse pressure is an independent determinant of vascular remodeling in the retinal circulation. Hypertension. 2013;61:1340–1345.
    1. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF III, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J, Ckd EPI. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–612.
    1. Chobanian AV. Impact of nonadherence to antihypertensive therapy. Circulation. 2009;120:1558–1560.
    1. Management of patient compliance in the treatment of hypertension. Report of the NHLBI Working Group. Hypertension. 1982;4:415–423.

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