Should More Significance Be Granted to Medication Response to Antihypertensives in Patients With Resistant Hypertension? Kai Liu, Di Shi and Xiaoping Chen Hypertension. 2014;63:e83; originally published online February 24, 2014; doi: 10.1161/HYPERTENSIONAHA.113.03092 Hypertension is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2014 American Heart Association, Inc. All rights reserved. Print ISSN: 0194-911X. Online ISSN: 1524-4563
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://hyper.ahajournals.org/content/63/4/e83
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Hypertension can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Hypertension is online at: http://hyper.ahajournals.org//subscriptions/
Downloaded from http://hyper.ahajournals.org/ at University Of Melbourne Library on September 13, 2014
Letter to the Editor Letters to the Editor will be published, if suitable, as space permits. They should not exceed 500 words (typed double-spaced) plus 5 references in length and may be subject to editing or abridgment.
Should More Significance Be Granted to Medication Response to Antihypertensives in Patients With Resistant Hypertension? To the Editor: In a recent thesis published in the journal, Calhoun et al1 presumed that although resistant hypertension (RH) is relatively common among treated patients with hypertension, true antihypertensive treatment failure is rare. We are grateful to Calhoun et al for their worthy efforts to provide significant information about the prevalence of refractory hypertension. Our next task is to figure out whether true antihypertensive treatment failure is common in treated patients with hypertension. About the article, we have to maintain reservations about the definition of RH. More importantly, the article causes our reflection on medication response evaluation in RH-therapy. In the journal, Calhoun et al defined RH as patients whose blood pressure (BP) measures ≥140/90 mm Hg, despite being treated with ≥3 antihypertensives with no changes in medication for a minimum of 2 weeks. It is closer to that of apparent RH ascribed in 2013 ESH/ESC (European Society of Hypertension/European Society of Cardiology) guidelines of hypertension without mentioning whether diuretics are prescribed and white coat hypertension are excluded. Meanwhile, on the basis of 2008 American Heart Association criteria, we conclude that instead of 2 weeks, antihypertensive medications should be ≥1 month. Patients enrolled in the study of Daugherty reported that more than half of them, with uncontrolled hypertension on 3 classes of antihypertensives prescribed for ≥1 month at baseline, had their BP controlled in 1 year later,2 which implies importance in identification of response in pharmacotherapy. Therefore, we observe that clinical BP remaining ≥140/90 mm Hg after treatment with ≥3 different antihypertensive drugs not necessarily as the end of medication, but an open-end for many unanswered questions (eg, the ideal constituents of multidrug regimens, the most effective drug in RH treatment). Also of note, therapeutic inertia of physicians was more marked in patients with apparent treatment-RH.3 In fact, many interesting phenomena provide clues for an urge to reassess the effects of pharmacotherapy or drug regimens response in patients with RH, which leaves substantial leeway for improving BP control in treatment-RH. Some include the following: (1) effects of pharmacogenomics on BP in response to thiazide diuretics, which may provide guidance on adjustment of diuretics4; (2) although not designed for epidemiological investigation on RH, the analyses of HOT-CHINA study recently
illustrates the rate of RH in China is much lower, only 1.9%, than reported previously, which suggests that racial factor affect, at least to some extents, the sensitivity to calcium channel blocker, especially in Chinese Han nationality population5; and (3) baseline plasma rennin activity and aldosterone/renin ratio could play a part in identifying in RH treatment, assessing for which treatment spironolactone is most effective, as assumed in ASPIRANT (Addition of Spironolactone in Patients With Resistant Arterial Hypertension) study. In conclusion, the true prevalence of RH might actually be greatly overestimated, and we promote here that more significance should, and needs to be granted to the identification of medication response in RH exploration, which, most probably, would fill the gap between apparent antihypertensive treatment failure and true antihypertensive treatment failure.
Disclosures None. Kai Liu Di Shi Xiaoping Chen Department of Cardiology West China Hospital Sichuan University Chengdu, China 1. Calhoun DA, Booth JN III, Oparil S, Irvin MR, Shimbo D, Lackland DT, Howard G, Safford MM, Muntner P. Refractory hypertension: determination of prevalence, risk factors, and comorbidities in a large, population- based cohort. Hypertension.2014;63:e84. 2. Daugherty SL, Powers JD, Magid DJ, Tavel HM, Masoudi FA, Margolis KL, O’Connor PJ, Selby JV, Ho PM. Incidence and prognosis of resistant hypertension in hypertensive patients. Circulation. 2012;125:1635–1642. 3. Waeber B, Feihl F. Do optimal antihypertensive drug regimens allow blood pressure normalization in all patients with resistant hypertension? Hypertension. 2013;62:680–681. 4. Turner ST, Boerwinkle E, O’Connell JR, et al. Genomic association analysis of common variants influencing antihypertensive response to hydrochlorothiazide. Hypertension. 2013;62:391–397. 5. Ma W, Zhang Y; HOT-CHINA Working Group. Low rate of resistant hypertension in Chinese patients with hypertension: an analysis of the HOT-CHINA study. J Hypertens. 2013;31:2386–2390.
(Hypertension. 2014;63:e83.) © 2014 American Heart Association, Inc. Hypertension is available at http://hyper.ahajournals.org
DOI: 10.1161/HYPERTENSIONAHA.113.03092
Downloaded from http://hyper.ahajournals.org/ at University Of Melbourne Library on September 13, 2014 e83
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://hyper.ahajournals.org/content/63/4/e83
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Hypertension can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Hypertension is online at: http://hyper.ahajournals.org//subscriptions/
Downloaded from http://hyper.ahajournals.org/ at University Of Melbourne Library on September 13, 2014
Letter to the Editor Letters to the Editor will be published, if suitable, as space permits. They should not exceed 500 words (typed double-spaced) plus 5 references in length and may be subject to editing or abridgment.
Should More Significance Be Granted to Medication Response to Antihypertensives in Patients With Resistant Hypertension? To the Editor: In a recent thesis published in the journal, Calhoun et al1 presumed that although resistant hypertension (RH) is relatively common among treated patients with hypertension, true antihypertensive treatment failure is rare. We are grateful to Calhoun et al for their worthy efforts to provide significant information about the prevalence of refractory hypertension. Our next task is to figure out whether true antihypertensive treatment failure is common in treated patients with hypertension. About the article, we have to maintain reservations about the definition of RH. More importantly, the article causes our reflection on medication response evaluation in RH-therapy. In the journal, Calhoun et al defined RH as patients whose blood pressure (BP) measures ≥140/90 mm Hg, despite being treated with ≥3 antihypertensives with no changes in medication for a minimum of 2 weeks. It is closer to that of apparent RH ascribed in 2013 ESH/ESC (European Society of Hypertension/European Society of Cardiology) guidelines of hypertension without mentioning whether diuretics are prescribed and white coat hypertension are excluded. Meanwhile, on the basis of 2008 American Heart Association criteria, we conclude that instead of 2 weeks, antihypertensive medications should be ≥1 month. Patients enrolled in the study of Daugherty reported that more than half of them, with uncontrolled hypertension on 3 classes of antihypertensives prescribed for ≥1 month at baseline, had their BP controlled in 1 year later,2 which implies importance in identification of response in pharmacotherapy. Therefore, we observe that clinical BP remaining ≥140/90 mm Hg after treatment with ≥3 different antihypertensive drugs not necessarily as the end of medication, but an open-end for many unanswered questions (eg, the ideal constituents of multidrug regimens, the most effective drug in RH treatment). Also of note, therapeutic inertia of physicians was more marked in patients with apparent treatment-RH.3 In fact, many interesting phenomena provide clues for an urge to reassess the effects of pharmacotherapy or drug regimens response in patients with RH, which leaves substantial leeway for improving BP control in treatment-RH. Some include the following: (1) effects of pharmacogenomics on BP in response to thiazide diuretics, which may provide guidance on adjustment of diuretics4; (2) although not designed for epidemiological investigation on RH, the analyses of HOT-CHINA study recently
illustrates the rate of RH in China is much lower, only 1.9%, than reported previously, which suggests that racial factor affect, at least to some extents, the sensitivity to calcium channel blocker, especially in Chinese Han nationality population5; and (3) baseline plasma rennin activity and aldosterone/renin ratio could play a part in identifying in RH treatment, assessing for which treatment spironolactone is most effective, as assumed in ASPIRANT (Addition of Spironolactone in Patients With Resistant Arterial Hypertension) study. In conclusion, the true prevalence of RH might actually be greatly overestimated, and we promote here that more significance should, and needs to be granted to the identification of medication response in RH exploration, which, most probably, would fill the gap between apparent antihypertensive treatment failure and true antihypertensive treatment failure.
Disclosures None. Kai Liu Di Shi Xiaoping Chen Department of Cardiology West China Hospital Sichuan University Chengdu, China 1. Calhoun DA, Booth JN III, Oparil S, Irvin MR, Shimbo D, Lackland DT, Howard G, Safford MM, Muntner P. Refractory hypertension: determination of prevalence, risk factors, and comorbidities in a large, population- based cohort. Hypertension.2014;63:e84. 2. Daugherty SL, Powers JD, Magid DJ, Tavel HM, Masoudi FA, Margolis KL, O’Connor PJ, Selby JV, Ho PM. Incidence and prognosis of resistant hypertension in hypertensive patients. Circulation. 2012;125:1635–1642. 3. Waeber B, Feihl F. Do optimal antihypertensive drug regimens allow blood pressure normalization in all patients with resistant hypertension? Hypertension. 2013;62:680–681. 4. Turner ST, Boerwinkle E, O’Connell JR, et al. Genomic association analysis of common variants influencing antihypertensive response to hydrochlorothiazide. Hypertension. 2013;62:391–397. 5. Ma W, Zhang Y; HOT-CHINA Working Group. Low rate of resistant hypertension in Chinese patients with hypertension: an analysis of the HOT-CHINA study. J Hypertens. 2013;31:2386–2390.
(Hypertension. 2014;63:e83.) © 2014 American Heart Association, Inc. Hypertension is available at http://hyper.ahajournals.org
DOI: 10.1161/HYPERTENSIONAHA.113.03092
Downloaded from http://hyper.ahajournals.org/ at University Of Melbourne Library on September 13, 2014 e83
