Resistant hypertension? Assessment of adherence by toxicological urine analysis

Objective: Uncontrolled hypertension under antihypertensive multidrug regimen is not necessarily always true resistance. Incomplete adherence is one of several possible causes of uncontrolled hypertension. Nonadherence remains largely unrecognized and is falsely interpreted as treatment resistance, as it is difficult to confirm or exclude objectively. This is the first study assessing adherence in patients with apparent resistant hypertension systematically via toxicological urine screening. Methods: All patients referred from primary care physicians because of uncontrolled hypertension between 2004 and 2011 were analysed. Adherence was assessed in all patients with uncontrolled hypertension despite the concurrent use of at least four antihypertensive agents by using liquid chromatography-mass spectrometry analysis for antihypertensive drugs or their corresponding metabolites in urine. Results: A total of 375 patients with uncontrolled hypertension were referred. After optimization of drug therapy and exclusion of white coat hypertension, 108 patients met criteria for resistant hypertension. Of those, 15 patients had secondary causes of hypertension and 17 achieved goal blood pressure with quadruple antihypertensive therapy. Of the remaining 76 patients, 40 patients (53%) were found to be nonadherent. Among nonadherent patients, 30% had complete and 70% had incomplete adherence; 85% of the latter had taken less than 50% of drugs prescribed. Lack of adherence was almost evenly distributed between different classes of antihypertensive drugs. Conclusion: Low adherence was the most common cause of poor blood pressure control in patients with apparent resistant hypertension, being twice as frequent as secondary causes of hypertension. Incomplete adherence was far more common than complete nonadherence; thus, assessment of adherence in patients on multiple drug regime is only reliable when all drugs are included in assessment. Assessing adherence by toxicological urine screening is a useful tool in detecting low adherence, especially in the setting of multidrug regimen as a cause of apparently resistant hypertension.

[1]  Joshua T. Cohen,et al.  Cost-effectiveness and clinical effectiveness of catheter-based renal denervation for resistant hypertension. , 2012, Journal of the American College of Cardiology.

[2]  W. Elliott,et al.  What is the prevalence of resistant hypertension in the United States? , 2012, Current opinion in cardiology.

[3]  J. Banegas,et al.  Clinical differences between resistant hypertensives and patients treated and controlled with three or less drugs , 2012, Journal of hypertension.

[4]  G. Parati,et al.  ESH position paper: renal denervation - an interventional therapy of resistant hypertension. , 2012, Journal of hypertension.

[5]  W. Elliott.  Uncontrolled and Apparent Treatment Resistant Hypertension in the United States, 1988 to 2008 , 2012 .

[6]  B. Egan,et al.  Uncontrolled and Apparent Treatment Resistant Hypertension in the United States, 1988 to 2008 , 2011, Circulation.

[7]  Stephen D. Persell.  Prevalence of Resistant Hypertension in the United States, 2003–2008 , 2011, Hypertension.

[8]  D. Calhoun,et al.  Resistant hypertension: bad and getting worse. , 2011, Hypertension.

[9]  Sebastian Schneeweiss,et al.  The implications of therapeutic complexity on adherence to cardiovascular medications. , 2011, Archives of internal medicine.

[10]  J. Banegas,et al.  Clinical Features of 8295 Patients With Resistant Hypertension Classified on the Basis of Ambulatory Blood Pressure Monitoring , 2011, Hypertension.

[11]  M. Woodward,et al.  Meta-Analysis: Impact of Drug Class on Adherence to Antihypertensives , 2011, Circulation.

[12]  P. Sever,et al.  How common is true resistant hypertension? , 2011, Journal of Human Hypertension.

[13]  S. Oparil,et al.  Adherence and persistence with taking medication to control high blood pressure. , 2011, Journal of the American Society of Hypertension : JASH.

[14]  G. Divine,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) , 2010, Circulation.

[15]  H. Maurer.  Perspectives of Liquid Chromatography Coupled to Low- and High-Resolution Mass Spectrometry for Screening, Identification, and Quantification of Drugs in Clinical and Forensic Toxicology , 2010, Therapeutic drug monitoring.

[16]  R. Chapman,et al.  The cost and effectiveness of adherence‐improving interventions for antihypertensive and lipid‐lowering drugs * , 2009, International journal of clinical practice.

[17]  C. Benesch,et al.  Cost‐Effectiveness of Treating Resistant Hypertension With an Implantable Carotid Body Stimulator , 2009, Journal of clinical hypertension.

[18]  N. Kressin,et al.  Intensifying Therapy for Hypertension Despite Suboptimal Adherence , 2009, Hypertension.

[19]  J. Benner,et al.  The clinical and economic burden of nonadherence with antihypertensive and lipid-lowering therapy in hypertensive patients. , 2009, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[20]  U. Kuch,et al.  Criminal poisoning of commuters in Bangladesh: prospective and retrospective study. , 2008, Forensic science international.

[21]  D. Goff,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. , 2008, Circulation.

[22]  Daniel W. Jones,et al.  A Scientific Statement From the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research , 2008 .

[23]  John Urquhart,et al.  Adherence to prescribed antihypertensive drug treatments: longitudinal study of electronically compiled dosing histories , 2008, BMJ : British Medical Journal.

[24]  A. Dominiczak,et al.  2007 ESH-ESC Practice Guidelines for the Management of Arterial Hypertension: ESH-ESC Task Force on the Management of Arterial Hypertension. , 2007, Journal of hypertension.

[25]  Piotr Ponikowski,et al.  2007 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). , 2007, European heart journal.

[26]  A. Dominiczak,et al.  2007 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) , 2007, European heart journal.

[27]  A. Christophersen,et al.  Simultaneous determination of 6 beta-blockers, 3 calcium-channel antagonists, 4 angiotensin-II antagonists and 1 antiarrhythmic drug in post-mortem whole blood by automated solid phase extraction and liquid chromatography mass spectrometry. Method development and robustness testing by experimental d , 2007, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[28]  Peter A. Ubel,et al.  Misperceptions about β-blockers and diuretics , 2003, Journal of General Internal Medicine.

[29]  B. Dowd,et al.  Relationship of the magnitude of member cost-share and medication persistence with newly initiated renin angiotensin system blockers. , 2007, Journal of managed care pharmacy : JMCP.

[30]  V. Durkalski,et al.  Therapeutic Inertia Is an Impediment to Achieving the Healthy People 2010 Blood Pressure Control Goals , 2006, Hypertension.

[31]  A. Lippman.  Adherence to medication. , 2005, The New England journal of medicine.

[32]  A. de Boer,et al.  Rate and determinants of 10-year persistence with antihypertensive drugs , 2005, Journal of hypertension.

[33]  R. Verbrugge,et al.  Impact of Medication Adherence on Hospitalization Risk and Healthcare Cost , 2005, Medical care.

[34]  H. Black,et al.  Resistant hypertension revisited: a comparison of two university-based cohorts. , 2005, American journal of hypertension.

[35]  E. Vuori,et al.  Application of accurate mass measurement to urine drug screening. , 2005, Journal of analytical toxicology.

[36]  F. Peters,et al.  Screening for library-assisted identification and fully validated quantification of 22 beta-blockers in blood plasma by liquid chromatography-mass spectrometry with atmospheric pressure chemical ionization. , 2004, Journal of chromatography. A.

[37]  Bill Mongelluzzo.  BAD, AND GETTING WORSE , 2004 .

[38]  T Fahey,et al.  Interventions for improving adherence to treatment in patients with high blood pressure in ambulatory settings (Review) , 2018 .

[39]  G. D. Johnston,et al.  Comparison of the effects of a 7-day period of non-compliance on blood pressure control using three different antihypertensive agents , 2004, Journal of hypertension.

[40]  Daniel W. Jones,et al.  Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. , 2003, Hypertension.

[41]  Daniel W. Jones,et al.  The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. , 2003, JAMA.

[42]  M. Burnier,et al.  Monitoring compliance in resistant hypertension: an important step in patient management. , 2003, Journal of hypertension. Supplement : official journal of the International Society of Hypertension.

[43]  E. Kumpusalo,et al.  Factors related to poor control of blood pressure with antihypertensive drug therapy. , 2003, Blood pressure.

[44]  D. Asch,et al.  Misperceptions about beta-blockers and diuretics: a national survey of primary care physicians. , 2003, Journal of general internal medicine.

[45]  B. Davis,et al.  Success and predictors of blood pressure control in diverse North American settings: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). , 2002, Journal of clinical hypertension.

[46]  W. Cushman,et al.  The Effect of a Losartan‐Based Treatment Regimen on Isolated Systolic Hypertension , 2002, Journal of clinical hypertension.

[47]  F. Magrini,et al.  High prevalence of cardiac and extracardiac target organ damage in refractory hypertension , 2001, Journal of hypertension.

[48]  M. Burnier,et al.  Electronic compliance monitoring in resistant hypertension: the basis for rational therapeutic decisions , 2001, Journal of hypertension.

[49]  J. Weinman,et al.  Patients' beliefs about prescribed medicines and their role in adherence to treatment in chronic physical illness. , 1999, Journal of psychosomatic research.

[50]  H. Maurer,et al.  Systematic toxicological analysis procedures for acidic drugs and/or metabolites relevant to clinical and forensic toxicology and/or doping control. , 1999, Journal of chromatography. B, Biomedical sciences and applications.

[51]  T. Mengden,et al.  Changes in antihypertensive therapy--the role of adverse effects and compliance. , 1998, Blood pressure.

[52]  J. Cramer,et al.  Compliance declines between clinic visits. , 1990, Archives of internal medicine.

[53]  M. Weinberger.  Diuretics and Their Side Effects Dilemma in the Treatment of Hypertension , 1988, HYPERTENSION.

[54]  H. Maurer,et al.  Identification and differentiation of beta-blockers and their metabolites in urine by computerized gas chromatography-mass spectrometry. , 1986, Journal of chromatography.

[55]  H. Craig.  Accuracy of indirect measures of medication compliance in hypertension. , 1985, Research in nursing & health.

[56]  W. Carter,et al.  Screening for noncompliance among patients with hypertension: is self-report the best available measure? , 1981, Medical care.

[57]  R B Haynes,et al.  Predicting compliance with a regimen of digoxin therapy in family practice. , 1980, Canadian Medical Association journal.

[58]  R. Carey,et al.  Estimating Compliance with Diuretic Therapy: Urinary Hydrochlorothiazide‐Creatinine Ratios in Normal Subjects , 1979, Hypertension.