International Journal of Cardiology 172 (2014) e309–e310

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Letter to the Editor

Pseudoresistant hypertension due to poor medication adherence Alfredo Dias de Oliveira-Filho a,b,⁎, Francisco A. Costa d, Sabrina Joany Felizardo Neves b, Divaldo Pereira de Lyra Junior a, Donald E. Morisky c a

Laboratory of Teaching and Research in Social Pharmacy (LEPFS), Federal University of Sergipe, Brazil School of Nursery and Pharmacy (ESENFAR), Federal University of Alagoas, Brazil University of California Los Angeles, Fielding School of Public Health, Los Angeles, CA, USA d Hospital do Açúcar, Alagoas, Brazil b c

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Article history: Received 9 November 2013 Accepted 28 December 2013 Available online 11 January 2014 Keywords: Resistant hypertension Medication adherence Pseudo-resistant hypertension

Resistant hypertension (RHTN) can be defined as the failure to achieve the goal blood pressure (less than 140/90 mm Hg, for the overall population, and less than 130/80 mm Hg for those with diabetes mellitus, or chronic kidney disease) when a patient adheres to a combination of at least 3 optimally dosed antihypertensive drugs of different classes, one of which should ideally be a diuretic [1]. This definition does not apply to patients who have been recently diagnosed with hypertension [2]. Patients requiring four or more antihypertensive medications – even if controlled – are also classified as having resistant hypertension [3]. Initially, a large proportion of patients were considered to be resistant hypertensive patients. Based on clinical trials during which participants were aggressively titrated to reach a target BP, the prevalence of RHTN was estimated to be 20% to 30% [2]. However, many studies have determined RHTN based on the fact that medication adherence, drug prescription and blood pressure measures were optimal. Evaluation of patients with resistive hypertension should first confirm that they have true RHTN by ruling out or correcting factors associated with pseudo-resistance which is the appearance of a lack of BP control caused by inaccurate measurement of BP, inappropriate drug choices/doses, non-adherence to prescribed therapy or white-coat effect [3,4]. Since a significant part of patients with RHTN was actually considered patients with “pseudo-resistant” hypertension, prevalence of RHTN has been reestimated at below 15% [5]. ⁎ Corresponding author at: School of Nursery and Pharmacy (ESENFAR), Federal University of Alagoas, Brazil. Tel./fax: +55 21 82 3214 1154. E-mail addresses: [email protected] (A.D. de Oliveira-Filho), [email protected] (F.A. Costa), [email protected] (S.J.F. Neves), [email protected] (D.P. de Lyra Junior), [email protected] (D.E. Morisky).

0167-5273/$ – see front matter © 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.12.181

The exclusion of patients with pseudo-resistance because of nonadherence with prescribed antihypertensive medications is recognized as a major methodological strength, and this determination has been lacking in prior epidemiologic assessments of RHTN [5]. In an investigation to determine the association between adherence to antihypertensive treatment and BP control in hypertensive outpatients we observed that 152 (43.9%) out of 359 patients did not adhere to antihypertensive therapy; 40 patients (11.1%) met criteria for RHTN. Since “pseudoresistance” is commonly misdiagnosed as resistant hypertension, in our sample, 98 out of 157 (62.4%) patients with uncontrolled BP and appropriate antihypertensive treatment were nonadherers and could be diagnosed as resistant hypertensive patients. These data indicate that non-adherence is an important, yet littleknown, problem among patients with RHTN. According to Daugherty et al. [6], prior studies on resistant hypertension are limited by failure to apply a uniform definition of resistant hypertension, a lack of longitudinal blood pressure data and an inability to identify “pseudo-resistant” hypertension due to poor medication adherence. Thus, a standardized protocol was used to measure BP by trained pairs of pharmacy students and health community agents, the values of systolic (SBP) and diastolic (DBP) blood pressure were obtained by the mean of six blood pressure measurements, carried out by the research team during three visits over a two week period, using mercury sphygmomanometers calibrated with a minimum interval of 10 min between each double measurement. To reduce the influence of the white-coat effect the measurements were taken at the patients' homes [7]. Adherence was assessed using a validated version in Portuguese of the 8-item Morisky Medication Adherence Scale (MMAS8) [8]. In this study, the patients were considered adherent if they had a score greater than or equal to 6 in the MMAS-8 [9]. Informed consent was obtained from each patient and The Federal University of Alagoas institutional review board approved the study protocol and consent form. It is important to consider that the proportion of non-adherent patients could be even higher, as the self-reporting methods have as major limitation the underestimation of the number of non-adherent individuals. However, self-reporting scales are usually simple, rapid, noninvasive and economical methods that can provide a real-time opinion about the adherence behavior of patients and potential reasons for non-adherence. We believe that the diagnosis of resistant hypertension should include a fundamental clinical step, which is the investigation of non-adherence and its causes, especially among individuals with

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low health-related quality of life, who are more likely to have lower adherence to antihypertensive medications [10]. It may facilitate the successful treatment of hypertension and avoid expensive and/or invasive therapeutic approaches, such as excessive antihypertensive therapy (although polypharmacy is difficult to avoid because blood pressure can be controlled by using one drug in only about 50% of patients [5]), electrical stimulation of carotid baroreceptors, catheter-based renal denervation and recent drug therapies (e.g., selective endothelin type A compounds, such as darusentan) [4]. In conclusion, nonadherence to prescribed antihypertensives seems to be a relevant if not the main cause of pseudoresistant hypertension. The identification and removal of this factor may contribute to normalize BP levels and, thus, to rule out the diagnosis of resistant hypertension, avoiding overtreatment and excessive/expensive evaluation.

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[9]

References [10] [1] Calhoun DA, Jones D, Textor S, et al. American Heart Association Professional Education Committee. 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 Jun 24;117(25):e510–26. Moser M, Setaro JF. Clinical practice. Resistant or difficult-to-control hypertension. N Engl J Med 2006 Jul 27;355(4):385–92. Pimenta E, Calhoun DA, Oparil S. Mechanisms and treatment of resistant hypertension. Arq Bras Cardiol 2007 Jun;88(6):683–92. Makris A, Seferou M, Papadopoulos DP. Resistant hypertension workup and approach to treatment. Int J Hypertens 2010 Dec 26;2011:598694. Pimenta E, Calhoun DA. Resistant hypertension: incidence, prevalence, and prognosis. Circulation 2012 Apr 3;125(13):1594–6. Daugherty SL, Powers JD, Magid DJ, et al. Incidence and prognosis of resistant hypertension in hypertensive patients. Circulation 2012 Apr 3;125(13):1635–42. Khan TV, Khan SS, Akhondi A, Khan TW. White coat hypertension: relevance to clinical and emergency medical services personnel. MedGenMed 2007 Mar 13;9(1):52. Oliveira-Filho AD, Barreto-Filho JA, Neves SJ, Lyra Junior DP. Association between the 8-item Morisky Medication Adherence Scale (MMAS-8) and blood pressure control. Arq Bras Cardiol 2012 Jul;99(1):649–58. Morisky DE, Ang A, Krousel-Wood M, Ward HJ. Predictive validity of a medication adherence measure in an outpatient setting. J Clin Hypertens (Greenwich) 2008 May;10(5):348–54. Zyoud SH, Al-Jabi SW, Sweileh WM, et al. Health-related quality of life associated with treatment adherence in patients with hypertension: a cross-sectional study. Int J Cardiol 2013 Oct 3;168(3):2981–3.

Pseudoresistant hypertension due to poor medication adherence.

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