Advertisement

Drug Adherence in Resistant Hypertension

  • Idir Hamdidouche
  • Vincent Jullien
  • Stéphane Laurent
  • Michel Azizi
Chapter
Part of the Updates in Hypertension and Cardiovascular Protection book series (UHCP)

Abstract

Non-adherence to antihypertensive treatment is recognized as a major factor affecting their effectiveness in hypertensive patients contributing to treatment resistance. Indeed, non-adherence is highly prevalent in patients with resistant hypertension. However, it is often overlooked because the methods to assess non-adherence are partly unreliable and thus limit their use in clinical practice. Non-adherence to treatment can affect daily patient management, resulting in inappropriate, costly, and potentially harmful treatment and loss of benefits expected from antihypertensive drugs. Indeed, non-adherence is associated with poor cardiovascular, cerebrovascular, and renal outcomes. Thus, improved screening tools, including therapeutic drug monitoring, are needed to detect non-adherence in patients with resistant hypertension, thus enabling appropriate interventions to improve drug adherence and avoid unnecessary treatment intensification. Given the expanding population with uncontrolled and resistant hypertension and emerging cost–benefits of adherence, addressing non-adherence to prescribed antihypertensive therapy is a top priority.

Keywords

Resistant hypertension Antihypertensive drugs Drug adherence Therapeutic drug monitoring Cardiovascular outcomes 

References

  1. 1.
    ESH/ESC Task Force for the Management of Arterial Hypertension. 2013 Practice guidelines for the management of arterial hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC): ESH/ESC Task Force for the Management of Arterial Hypertension. J Hypertens. 2013;31(10):1925–38.CrossRefGoogle Scholar
  2. 2.
    Krause T, Lovibond K, Caulfield M, McCormack T, Williams B, Guideline Development Group. Management of hypertension: summary of NICE guidance. BMJ. 2011;343:d4891.CrossRefPubMedGoogle Scholar
  3. 3.
    Judd E, Calhoun DA. Apparent and true resistant hypertension: definition, prevalence and outcomes. J Hum Hypertens. 2014;28(8):463–8.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Achelrod D, Wenzel U, Frey S. Systematic review and meta-analysis of the prevalence of resistant hypertension in treated hypertensive populations. Am J Hypertens. 2015;28(3):355–61.CrossRefPubMedGoogle Scholar
  5. 5.
    Calhoun DA, Jones D, Textor S, Goff DC, Murphy TP, Toto RD, et al. Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Circulation. 2008;117(25):e510–26.CrossRefPubMedGoogle Scholar
  6. 6.
    Myat A, Redwood SR, Qureshi AC, Spertus JA, Williams B. Resistant hypertension. BMJ. 2012;345:e7473.CrossRefPubMedGoogle Scholar
  7. 7.
    Vongpatanasin W. Resistant hypertension: a review of diagnosis and management. JAMA. 2014;311(21):2216–24.CrossRefGoogle Scholar
  8. 8.
    Cuspidi C, Macca G, Sampieri L, Michev I, Salerno M, Fusi V, et al. High prevalence of cardiac and extracardiac target organ damage in refractory hypertension. J Hypertens. 2001;19(11):2063–70.CrossRefPubMedGoogle Scholar
  9. 9.
    Egan BM, Zhao Y, Axon RN, Brzezinski WA, Ferdinand KC. Uncontrolled and apparent treatment resistant hypertension in the United States, 1988 to 2008. Circulation. 2011;124(9):1046–58.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Oliveria SA, Lapuerta P, McCarthy BD, L’Italien GJ, Berlowitz DR, Asch SM. Physician-related barriers to the effective management of uncontrolled hypertension. Arch Intern Med. 2002;162(4):413–20.CrossRefPubMedGoogle Scholar
  11. 11.
    Sarafidis PA, Bakris GL. Resistant hypertension: an overview of evaluation and treatment. J Am Coll Cardiol. 2008;52(22):1749–57.CrossRefPubMedGoogle Scholar
  12. 12.
    Williams B, MacDonald TM, Morant S, Webb DJ, Sever P, McInnes G, et al. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet. 2015;386(10008):2059–68.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Zhao D, Liu H, Dong P, Zhao J. A meta-analysis of add-on use of spironolactone in patients with resistant hypertension. Int J Cardiol. 2017;233:113–7.CrossRefPubMedGoogle Scholar
  14. 14.
    Vrijens B, De Geest S, Hughes DA, Przemyslaw K, Demonceau J, Ruppar T, et al. A new taxonomy for describing and defining adherence to medications. Br J Clin Pharmacol. 2012;73(5):691–705.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Vrijens B, Antoniou S, Burnier M, de la Sierra A, Volpe M. Current situation of medication adherence in hypertension. Front Pharmacol. 2017;8:100.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353(5):487–97.CrossRefPubMedGoogle Scholar
  17. 17.
    Burnier M, Schneider MP, Chioléro A, Stubi CL, Brunner HR. Electronic compliance monitoring in resistant hypertension: the basis for rational therapeutic decisions. J Hypertens. 2001;19(2):335–41.CrossRefPubMedGoogle Scholar
  18. 18.
    Brinker S, Pandey A, Ayers C, Price A, Raheja P, Arbique D, et al. Therapeutic drug monitoring facilitates blood pressure control in resistant hypertension. J Am Coll Cardiol. 2014;63(8):834–5.CrossRefPubMedGoogle Scholar
  19. 19.
    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(1):87–90.CrossRefPubMedGoogle Scholar
  20. 20.
    Jung O, Gechter JL, Wunder C, Paulke A, Bartel C, Geiger H, et al. Resistant hypertension? Assessment of adherence by toxicological urine analysis. J Hypertens. 2013;31(4):766–74.CrossRefPubMedGoogle Scholar
  21. 21.
    Tomaszewski M, White C, Patel P, Masca N, Damani R, Hepworth J, et al. 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(11):855–61.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Hamdidouche I, Jullien V, Billaud EM, Boutouyrie P, Azizi M, Laurent S. Routine urinary detection of antihypertensive drugs for estimation of adherence to treatment: a cross sectional study. J Hypertens. 2015;33(Suppl 1):e93.CrossRefGoogle Scholar
  23. 23.
    Patel P, Gupta PKC, White CMJ, Stanley AG, Williams B, Tomaszewski M. Screening for non-adherence to antihypertensive treatment as a part of the diagnostic pathway to renal denervation. J Hum Hypertens. 2016;30(6):368–73.CrossRefPubMedGoogle Scholar
  24. 24.
    Hamdidouche I, Jullien V, Boutouyrie P, Billaud E, Azizi M, Laurent S. Drug adherence in hypertension: from methodological issues to cardiovascular outcomes. J Hypertens. 2017;35(6):1133–44.CrossRefPubMedGoogle Scholar
  25. 25.
    Burnier M, Wuerzner G. Drug adherence monitoring in clinical trials: a necessity for a correct assessment of the efficacy and safety of antihypertensive therapies. J Hypertens. 2015;33(12):2395–8.CrossRefPubMedGoogle Scholar
  26. 26.
    de Jager RL, de Beus E, Beeftink MMA, Sanders MF, Vonken E-J, Voskuil M, et al. Impact of medication adherence on the effect of renal denervation: the SYMPATHY trial. Hypertension. 2017;69(4):678–84.CrossRefPubMedGoogle Scholar
  27. 27.
    Azizi M, Pereira H, Hamdidouche I, Gosse P, Monge M, Bobrie G, et al. Adherence to antihypertensive treatment and the blood pressure lowering effects of renal denervation in the renal denervation for hypertension (DENERHTN) trial. Circulation. 2016;134(12):847–57.CrossRefPubMedGoogle Scholar
  28. 28.
    Beaussier H, Boutouyrie P, Bobrie G, Frank M, Laurent S, Coudoré F, et al. True antihypertensive efficacy of sequential nephron blockade in patients with resistant hypertension and confirmed medication adherence. J Hypertens. 2015;33(12):2526–33.CrossRefPubMedGoogle Scholar
  29. 29.
    Mahfoud F, Böhm M, Azizi M, Pathak A, Durand Zaleski I, Ewen S, et al. Proceedings from the European clinical consensus conference for renal denervation: considerations on future clinical trial design. Eur Heart J. 2015;36(33):2219–27.CrossRefPubMedGoogle Scholar
  30. 30.
    Burnier M, Wuerzner G, Struijker-Boudier H, Urquhart J. Measuring, analyzing, and managing drug adherence in resistant hypertension. Hypertension. 2013;62(2):218–25.CrossRefPubMedGoogle Scholar
  31. 31.
    Morisky DE, Ang A, Krousel-Wood M, Ward HJ. Predictive validity of a medication adherence measure in an outpatient setting. J Clin Hypertens. 2008;10(5):348–54.CrossRefGoogle Scholar
  32. 32.
    Azizi M, Ménard J, Peyrard S, Lièvre M, Marre M, Chatellier G. Assessment of patients’ and physicians’ compliance to an ACE inhibitor treatment based on urinary N-acetyl Ser-Asp-Lys-Pro determination in the Noninsulin-Dependent Diabetes, Hypertension, Microalbuminuria, Proteinuria, Cardiovascular Events, and Ramipril (DIABHYCAR) study. Diabetes Care. 2006;29(6):1331–6.CrossRefPubMedGoogle Scholar
  33. 33.
    Berra E, Azizi M, Capron A, Høieggen A, Rabbia F, Kjeldsen SE, et al. Evaluation of adherence should become an integral part of assessment of patients with apparently treatment-resistant hypertension. Hypertension. 2016;68(2):297–306.CrossRefPubMedGoogle Scholar
  34. 34.
    Pandey A, Raza F, Velasco A, Brinker S, Ayers C, Das SR, et al. Comparison of Morisky Medication Adherence Scale with therapeutic drug monitoring in apparent treatment-resistant hypertension. J Am Soc Hypertens. 2015;9(6):420–6.e2.CrossRefPubMedGoogle Scholar
  35. 35.
    Kjeldsen SE, Os I. Cost-effectiveness of therapeutic drug monitoring in patients with resistant hypertension and improving patients’ adherence. J Hypertens. 2014;32(12):2357–8.CrossRefPubMedGoogle Scholar
  36. 36.
    Burnier M. Medication adherence and persistence as the cornerstone of effective antihypertensive therapy. Am J Hypertens. 2006;19(11):1190–6.CrossRefPubMedGoogle Scholar
  37. 37.
    Bramley TJ, Gerbino PP, Nightengale BS, Frech-Tamas F. Relationship of blood pressure control to adherence with antihypertensive monotherapy in 13 managed care organizations. J Manag Care Pharm. 2006;12(3):239–45.PubMedGoogle Scholar
  38. 38.
    Mazzaglia G, Ambrosioni E, Alacqua M, Filippi A, Sessa E, Immordino V, et al. Adherence to antihypertensive medications and cardiovascular morbidity among newly diagnosed hypertensive patients. Circulation. 2009;120(16):1598–605.CrossRefPubMedGoogle Scholar
  39. 39.
    Perreault S, Dragomir A, White M, Lalonde L, Blais L, Bérard A. Better adherence to antihypertensive agents and risk reduction of chronic heart failure. J Intern Med. 2009;266(2):207–18.CrossRefPubMedGoogle Scholar
  40. 40.
    Perreault S, Dragomir A, Roy L, White M, Blais L, Lalonde L, et al. Adherence level of antihypertensive agents in coronary artery disease. Br J Clin Pharmacol. 2010;69(1):74–84.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Kettani F-Z, Dragomir A, Côté R, Roy L, Bérard A, Blais L, et al. Impact of a better adherence to antihypertensive agents on cerebrovascular disease for primary prevention. Stroke. 2009;40(1):213–20.CrossRefPubMedGoogle Scholar
  42. 42.
    Roy L, White-Guay B, Dorais M, Dragomir A, Lessard M, Perreault S. Adherence to antihypertensive agents improves risk reduction of end-stage renal disease. Kidney Int. 2013;84(3):570–7.CrossRefPubMedGoogle Scholar
  43. 43.
    Simpson SH, Eurich DT, Majumdar SR, Padwal RS, Tsuyuki RT, Varney J, et al. A meta-analysis of the association between adherence to drug therapy and mortality. BMJ. 2006;333(7557):15.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Chowdhury R, Khan H, Heydon E, Shroufi A, Fahimi S, Moore C, et al. Adherence to cardiovascular therapy: a meta-analysis of prevalence and clinical consequences. Eur Heart J. 2013;34(38):2940–8.CrossRefPubMedGoogle Scholar
  45. 45.
    Corrao G, Parodi A, Nicotra F, Zambon A, Merlino L, Cesana G, et al. Better compliance to antihypertensive medications reduces cardiovascular risk. J Hypertens. 2011;29(3):610–8.CrossRefPubMedGoogle Scholar
  46. 46.
    Daugherty SL, Powers JD, Magid DJ, Masoudi FA, Margolis KL, O’Connor PJ, et al. The association between medication adherence and treatment intensification with blood pressure control in resistant hypertension. Hypertension. 2012;60(2):303–9.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001;23(8):1296–310.CrossRefGoogle Scholar
  48. 48.
    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(15):1611–21.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Strauch B, Petrák O, Zelinka T, Rosa J, Somlóová Z, Indra T, et al. Precise assessment of noncompliance with the antihypertensive therapy in patients with resistant hypertension using toxicological serum analysis. J Hypertens. 2013;31(12):2455–61.CrossRefPubMedGoogle Scholar
  50. 50.
    Irvin MR, Shimbo D, Mann DM, Reynolds K, Krousel-Wood M, Limdi NA, et al. Prevalence and correlates of low medication adherence in apparent treatment-resistant hypertension. J Clin Hypertens (Greenwich). 2012;14(10):694–700.CrossRefGoogle Scholar
  51. 51.
    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(8):1708–15.CrossRefPubMedGoogle Scholar
  52. 52.
    Holt E, Joyce C, Dornelles A, Morisky D, Webber LS, Muntner P, et al. Sex differences in barriers to antihypertensive medication adherence: findings from the cohort study of medication adherence among older adults. J Am Geriatr Soc. 2013;61(4):558–64.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Cené CW, Dennison CR, Powell Hammond W, Levine D, Bone LR, Hill MN. Antihypertensive medication nonadherence in black men: direct and mediating effects of depressive symptoms, psychosocial stressors, and substance use. J Clin Hypertens. 2013;15(3):201–9.CrossRefGoogle Scholar
  54. 54.
    Marshall IJ, Wolfe CDA, McKevitt C. Lay perspectives on hypertension and drug adherence: systematic review of qualitative research. BMJ. 2012;345:e3953.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Knight EL, Bohn RL, Wang PS, Glynn RJ, Mogun H, Avorn J. Predictors of uncontrolled hypertension in ambulatory patients. Hypertension. 2001;38(4):809–14.CrossRefPubMedGoogle Scholar
  56. 56.
    Xie L, Frech-Tamas F, Marrett E, Baser O. A medication adherence and persistence comparison of hypertensive patients treated with single-, double- and triple-pill combination therapy. Curr Med Res Opin. 2014;30(12):2415–22.CrossRefPubMedGoogle Scholar
  57. 57.
    Misono AS, Cutrona SL, Choudhry NK, Fischer MA, Stedman MR, Liberman JN, et al. Healthcare information technology interventions to improve cardiovascular and diabetes medication adherence. Am J Manag Care. 2010;16(12 Suppl HIT):SP82–92.PubMedGoogle Scholar
  58. 58.
    Hernandez-Tejada MA, Campbell JA, Walker RJ, Smalls BL, Davis KS, Egede LE. Diabetes empowerment, medication adherence and self-care behaviors in adults with type 2 diabetes. Diabetes Technol Ther. 2012;14(7):630–4.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Ogedegbe G, Schoenthaler A. A systematic review of the effects of home blood pressure monitoring on medication adherence. J Clin Hypertens (Greenwich). 2006;8(3):174–80.CrossRefGoogle Scholar
  60. 60.
    Omboni S, Gazzola T, Carabelli G, Parati G. Clinical usefulness and cost effectiveness of home blood pressure telemonitoring: meta-analysis of randomized controlled studies. J Hypertens. 2013;31(3):455–67; discussion 467–8.CrossRefPubMedGoogle Scholar
  61. 61.
    Parati G, Stergiou G, O’Brien E, Asmar R, Beilin L, Bilo G, et al. European Society of Hypertension practice guidelines for ambulatory blood pressure monitoring. J Hypertens. 2014;32(7):1359–66.CrossRefPubMedGoogle Scholar
  62. 62.
    McManus RJ, Mant J, Haque MS, Bray EP, Bryan S, Greenfield SM, et al. Effect of self-monitoring and medication self-titration on systolic blood pressure in hypertensive patients at high risk of cardiovascular disease: the TASMIN-SR randomized clinical trial. JAMA. 2014;312(8):799–808.CrossRefPubMedGoogle Scholar
  63. 63.
    Nieuwlaat R, Wilczynski N, Navarro T, Hobson N, Jeffery R, Keepanasseril A, et al. Interventions for enhancing medication adherence. Cochrane Database Syst Rev. 2014;(11):CD000011.Google Scholar
  64. 64.
    Mistry N, Keepanasseril A, Wilczynski NL, Nieuwlaat R, Ravall M, Haynes RB, et al. Technology-mediated interventions for enhancing medication adherence. J Am Med Inform Assoc. 2015;22(e1):e177–93.CrossRefPubMedGoogle Scholar
  65. 65.
    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(7653):1114–7.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Christensen A, Osterberg LG, Hansen EH. Electronic monitoring of patient adherence to oral antihypertensive medical treatment: a systematic review. J Hypertens. 2009;27(8):1540–51.CrossRefPubMedGoogle Scholar
  67. 67.
    Hafezi H, Robertson TL, Moon GD, Au-Yeung K-Y, Zdeblick MJ, Savage GM. An ingestible sensor for measuring medication adherence. IEEE Trans Biomed Eng. 2015;62(1):99–109.CrossRefPubMedGoogle Scholar
  68. 68.
    Pladevall M, Brotons C, Gabriel R, Arnau A, Suarez C, de la Figuera M, et al. Multicenter cluster-randomized trial of a multifactorial intervention to improve antihypertensive medication adherence and blood pressure control among patients at high cardiovascular risk (the COM99 study). Circulation. 2010;122(12):1183–91.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Zeng F, Patel BV, Andrews L, Frech-Tamas F, Rudolph AE. Adherence and persistence of single-pill ARB/CCB combination therapy compared to multiple-pill ARB/CCB regimens. Curr Med Res Opin. 2010;26(12):2877–87.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Idir Hamdidouche
    • 1
    • 2
    • 3
  • Vincent Jullien
    • 1
    • 2
  • Stéphane Laurent
    • 1
    • 2
    • 3
  • Michel Azizi
    • 1
    • 2
    • 4
  1. 1.Department of Pharmacology and Hypertension UnitHopital Europeen Georges Pompidou, Assistance-Publique Hopitaux de ParisParisFrance
  2. 2.Paris-Descartes UniversityParisFrance
  3. 3.INSERM UMRS970ParisFrance
  4. 4.INSERM CIC1418ParisFrance

Personalised recommendations