Non-adherence to heart failure medications predicts clinical outcomes: assessment in a single spot urine sample by liquid chromatography-tandem mass spectrometry (results of a prospective multicentre study).
Adrenergic beta-Antagonists
/ therapeutic use
Angiotensin Receptor Antagonists
/ therapeutic use
Angiotensin-Converting Enzyme Inhibitors
/ therapeutic use
Chromatography, Liquid
Heart Failure
/ drug therapy
Humans
Prospective Studies
Stroke Volume
Tandem Mass Spectrometry
Ventricular Function, Left
All-cause mortality
Angiotensin receptor blockers
Angiotensin-converting enzyme inhibitors
BIOSTAT-CHF
Biochemical adherence screening
Heart failure
Non-adherence
β-blockers
Journal
European journal of heart failure
ISSN: 1879-0844
Titre abrégé: Eur J Heart Fail
Pays: England
ID NLM: 100887595
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
revised:
13
02
2021
received:
03
02
2021
accepted:
19
03
2021
pubmed:
25
3
2021
medline:
11
8
2021
entrez:
24
3
2021
Statut:
ppublish
Résumé
Liquid chromatography-mass spectrometry (LC-MS/MS) is an objective new technique to assess non-adherence to medications. We used this method to study the prevalence, predictors and outcomes of non-adherence in patients with heart failure with reduced left ventricular ejection fraction (HFrEF). This study included 1296 patients with HFrEF from BIOSTAT-CHF, a study that aimed to optimise guideline-recommended therapies. Angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists, β-blockers and loop diuretics were measured in a single spot urine sample at 9 months using LC-MS/MS. The relationship between medication non-adherence and the composite endpoint of all-cause death or heart failure hospitalisation, over a median follow-up of 21 months, was evaluated. Non-adherence to at least one prescribed medication was observed in 45.9% of patients. The strongest predictor of non-adherence was non-adherence to any of the other medication classes (P < 0.0005). Regional differences within Europe were observed. On multivariable analyses, non-adherence to ACEi/ARBs and β-blockers was associated with an increased risk of the composite endpoint [hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.09-1.95, P = 0.008 and HR 1.48, 95% CI 1.12-1.96, P = 0.006, respectively). Non-adherence to β-blockers was also associated with an increased risk of death (HR 2.48, 95% CI 1.67-3.68, P < 0.0005). Patients who were non-adherent to loop diuretics were healthier and had a decreased risk of the composite endpoint (HR 0.69, 95% CI 0.51-0.93, P = 0.014). Non-adherence to mineralocorticoid receptor antagonists was not related to any clinical outcome. Non-adherence to medications, assessed by a single urine test, is common and predicts clinical outcomes in patients with HFrEF.
Substances chimiques
Adrenergic beta-Antagonists
0
Angiotensin Receptor Antagonists
0
Angiotensin-Converting Enzyme Inhibitors
0
Banques de données
EudraCT
['2010-020808-29']
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1182-1190Informations de copyright
© 2021 European Society of Cardiology.
Références
Fitzgerald AA, Powers JD, Ho PM, Maddox TM, Peterson PN, Allen LA, Masoudi FA, Magid DJ, Havranek EP. Impact of medication nonadherence on hospitalizations and mortality in heart failure. J Card Fail 2011;17:664-669.
O'Meara E, Lewis E, Granger C, Dunlap ME, McKelvie RS, Probstfield JL, Young JB, Michelson EL, Ostergren J, Carlsson J, Olofsson B, McMurray J, Yusuf S, Swedberg K, Pfeffer MA. Patient perception of the effect of treatment with candesartan in heart failure. Results of the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) Programme. Eur J Heart Fail 2005;7:650-656.
Kolandaivelu K, Leiden BB, O'Gara PT, Bhatt DL. Non-adherence to cardiovascular medications. Eur Heart J 2014;35:3267-3276.
Oosterom-Calo R, van Ballegooijen AJ, Terwee CB, te Velde SJ, Brouwer IA, Jaarsma T, Brug J. Determinants of adherence to heart failure medication: a systematic literature review. Heart Fail Rev 2013;18:409-427.
Gislason GH, Rasmussen JN, Abildstrom SZ, Schramm TK, Hansen ML, Buch P, Sorensen R, Folke F, Gadsboll N, Rasmussen S, Kober L, Madsen M, Torp-Pedersen C. Persistent use of evidence-based pharmacotherapy in heart failure is associated with improved outcomes. Circulation 2007;116:737-744.
Wu JR, Moser DK, De Jong MJ, Rayens MK, Chung ML, Riegel B, Lennie TA. Defining an evidence-based cutpoint for medication adherence in heart failure. Am Heart J 2009;157:285-291.
Granger BB, Swedberg K, Ekman I, Granger CB, Olofsson B, McMurray JJ, Yusuf S, Michelson EL, Pfeffer MA; CHARM Investigators. Adherence to candesartan and placebo and outcomes in chronic heart failure in the CHARM programme: double-blind, randomised, controlled clinical trial. Lancet 2005;366:2005-2011.
Muzzarelli S, Brunner-La Rocca H, Pfister O, Foglia P, Moschovitis G, Mombelli G, Stricker H. Adherence to the medical regime in patients with heart failure. Eur J Heart Fail 2010;12:389-396.
Gupta P, Patel P, Horne R, Buchanan H, Williams B, Tomaszewski M. How to screen for non-adherence to antihypertensive therapy. Curr Hypertens Rep 2016;18:89-92.
Krueger K, Griese-Mammen N, Schubert I, Kieble M, Botermann L, Laufs U, Kloft C, Schulz M. In search of a standard when analyzing medication adherence in patients with heart failure using claims data: a systematic review. Heart Fail Rev 2018;23:63-71.
Nieuwlaat R, Wilczynski N, Navarro T, Hobson N, Jeffery R, Keepanasseril A, Agoritsas T, Mistry N, Iorio A, Jack S, Sivaramalingam B, Iserman E, Mustafa RA, Jedraszewski D, Cotoi C, Haynes RB. Interventions for enhancing medication adherence. Cochrane Database Syst Rev 2014;11:CD000011.
Fitzgerald RL, Rivera JD, Herold DA. Broad spectrum drug identification directly from urine, using liquid chromatography-tandem mass spectrometry. Clin Chem 1999;45:1224-1234.
Grebe SK, Singh RJ. LC-MS/MS in the clinical laboratory - where to from here? Clin Biochem Rev 2011;32:5-31.
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.
Brinker S, Pandey A, Ayers C, Price A, Raheja P, Arbique D, Das SR, Halm EA, Kaplan NM, Vongpatanasin W. Therapeutic drug monitoring facilitates blood pressure control in resistant hypertension. J Am Coll Cardiol 2014;63:834-835.
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.
Voors AA, Anker SD, Cleland JG, Dickstein K, Filippatos G, van der Harst P, Hillege HL, Lang CC, Ter Maaten JM, Ng L, Ponikowski P, Samani NJ, van Veldhuisen DJ, Zannad F, Zwinderman AH, Metra M. A systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure: rationale, design, and baseline characteristics of BIOSTAT-CHF. Eur J Heart Fail 2016;18:716-726.
NCAT. National Centre for Adherence Testing 2020. https://www.leicestersresearch.nhs.uk/about-us-2/facilities/national-centre-for-drug-adherence-testing (24 March 2021).
Moffat AC, Osselton DM, Widdop B, Watts J. Clarke's Analysis of Drugs and Poisons, 4th ed. London, UK: Pharmaceutical Press; 2011.
Lawson AJ, Shipman KE, George S, Dasgupta I. A novel ‘Dilute-and-Shoot’ liquid chromatography-tandem mass spectrometry method for the screening of antihypertensive drugs in urine. J Anal Toxicol 2016;40:17-27.
Lane D, Alghamdi R, Muscat M, Kaur MS, Davis T, Cole R, Patel P, Tomaszewski M, Gupta P. The diagnosis of non-adherence in hypertension using a urine biochemical screen is unaffected by drug pharmacokinetics. Eur Heart J 2019;40(Suppl 1):1424 (abstr).
Voors AA, Ouwerkerk W, Zannad F, van Veldhuisen DJ, Samani NJ, Ponikowski P, Ng LL, Metra M, Ter Maaten JM, Lang CC, Hillege HL, van der Harst P, Filippatos G, Dickstein K, Cleland JG, Anker SD, Zwinderman AH. Development and validation of multivariable models to predict mortality and hospitalization in patients with heart failure. Eur J Heart Fail 2017;19:627-634.
Pelouch R, Vorisek V, Furmanova V, Solar M. The assessment of serum drug levels to diagnose non-adherence in stable chronic heart failure patients. Acta Medica (Hradec Kralove) 2019;62:52-57.
Simpson J, Jackson CE, Haig C, Jhund PS, Tomaszewski M, Gardner RS, Tsorlalis Y, Petrie MC, McMurray JJV, Squire IB, Gupta P. Adherence to prescribed medications in patients with heart failure - insights from liquid chromatography-tandem mass spectrometry-based urine analysis. Eur Heart J Cardiovasc Pharmacother 2020 Jun 29. https://doi.org/10.1093/ehjcvp/pvaa071 [Epub ahead of print].
Garg R, Yusuf S. Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. Collaborative Group on ACE Inhibitor Trials. JAMA 1995;273:1450-1456.
Chatterjee S, Biondi-Zoccai G, Abbate A, D'Ascenzo F, Castagno D, Van Tassell B, Mukherjee D, Lichstein E. Benefits of beta blockers in patients with heart failure and reduced ejection fraction: network meta-analysis. BMJ 2013;346:f55.
Gupta P, Patel P, Bransilav S. Biochemical screening for non-adherence is associated with blood pressure reduction and imporvement in non-adherence. Hypertension 2017;70:1042-1048.
Patel P, Gupta P, Burns A, Mohamed AA, Cole R, Lane D, Seidu S, Khunti K. Biochemical urine testing of adherence to cardiovascular medications reveals high rates of nonadherence in people attending their annual review for type 2 diabetes. Diabetes Care 2019;42:1132-1135.
Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, Gonzalez-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2016;18:891-975.
Ekman I, Wolf A, Vaughan Dickson V, Bosworth HB, Granger BB. Unmet expectations of medications and care providers among patients with heart failure assessed to be poorly adherent: results from the Chronic Heart Failure Intervention to Improve MEdication Adherence (CHIME) study. Eur J Cardiovasc Nurs 2017;16:646-654.
Ruppar TM, Cooper PS, Mehr DR, Delgado JM, Dunbar-Jacob JM. Medication adherence interventions improve heart failure mortality and readmission rates: systematic review and meta-analysis of controlled trials. J Am Heart Assoc 2016;5:e002606.
van der Wal MH, Jaarsma T, Moser DK, Veeger NJ, van Gilst WH, van Veldhuisen DJ. Compliance in heart failure patients: the importance of knowledge and beliefs. Eur Heart J 2006;27:434-440.
Riegel B, Lee CS, Ratcliffe SJ, De Geest S, Potashnik S, Patey M, Sayers SL, Goldberg LR, Weintraub WS. Predictors of objectively measured medication nonadherence in adults with heart failure. Circ Heart Fail 2012;5:430-436.
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.
Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, Clement DL, Coca A, de Simone G, Dominiczak A, Kahan T, Mahfoud F, Redon J, Ruilope L, Zanchetti A, Kerins M, Kjeldsen SE, Kreutz R, Laurent S, Lip GY, McManus R, Narkiewicz K, Ruschitzka F, Schmieder RE, Shlyakhto E, Tsioufis C, Aboyans V, Desormais I. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J 2018;39:3021-3104.
Burns A, Lane D, Cole R, Patel P, Gupta P. Cardiovascular medication stability in urine for non-adhenrece screen by LC-MS/MS. J Anal Toxicol 2019;43:325-329.