Editorial

Progress in Treating Hypertension

Michael A. Weber, MD, Senior Editor; Nanette K. Wenger, MD, Editor in Chief

he treatment of hypertension by primary care physicians and cardiologists remains a major part of medical practice, but it is still clear that treatment results are far from optimal. This is especially so in older persons in whom it is often difficult to deal effectively with predominant systolic hypertension. Most of the available antihypertensive drug classes are reasonably efficacious in reducing blood pressure in the elderly, but achievement of true target levels (<140/90 mm Hg or even lower if diabetes, kidney disease, coronary disease, or heart failure are present) is most often not achieved by single-agent therapy. Recently, though, there has been some good news in this area. The US Food and Drug Administration (FDA) took a bold and encouraging step in November 2007, when for the first time it approved a fixed-dose combination (an angiotensin receptor blocker plus a diuretic) as initial therapy for patients in whom it is judged likely that multiple drugs will be required to achieve goal blood pressure levels. Major national and international guidelines for the treatment of hypertension had recommended 4 or 5 years ago that this strategy be employed in patients whose starting blood pressure levels were 20/10 mm Hg or more above the desired targets.1,2 Even so, the FDA approval of a particular fixed combination (irbesartan plus hydrochlorothiazide), which almost certainly will be followed by a similar indication for several other antihypertensive combination therapies, will now recruit the considerable support of the pharmaceutical industry in advancing a strategy that is likely to promote improved hypertension control rates. The value of combination therapy for achieving blood pressure goals in older patients is highlighted by the article of Cushman and colleagues3 in this issue of The American Journal of Geriatric Cardiology. This research was based in patients

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with hypertension in whom blood pressure control was not achieved when treated with singleagent therapy. When exposed to optimal doses of an irbesartan/hydrochlorothiazide combination (by chance, the same combination that was recently approved for initial therapy by the FDA), very satisfactory control rates for both systolic and diastolic blood pressure were reached in a cohort of elderly hypertensive patients. Realistically, however, hypertension control rates in community practice will not usually match those reported in clinical trials. In some cases, for instance, patients started on initial treatment for hypertension may not fully understand the need for further adjustments or additions to their regimens to achieve satisfactory blood pressure levels. Indeed, patients in high-volume practices, where exposure to practitioners can often be somewhat perfunctory, may even regard the substitution or addition of antihypertensive agents as an indication that physicians may have chosen hastily or unwisely in their initial drug selections. Also, in the real world it is sometimes impractical or even unaffordable for patients, particularly those with jobs or responsibilities of their own, to make repeated visits to the office or clinic to deal with their blood pressure problems. In large clinics that often have continuing turnovers of treating physicians, there can also be the further problem of inconsistent objectives and strategies. It is noteworthy that physicians are not always fully committed to achieving blood pressure goals.4 Sometimes they are concerned about possible adverse effects of drugs and make a conscious decision to accept an inadequate blood pressure response rather than take the risk of precipitating symptomatic complaints. Moreover, unlike the situation in clinical trials, where the hypertensive patients being studied are often in reasonably good general health, those seen in clinical practice often have multiple other conditions that also require drug therapy, prompting

EDITORIAL

THE AMERICAN JOURNAL OF GERIATRIC CARDIOLOGY 2008 VOL. 17 NO. 1

The American Journal of Geriatric Cardiology (ISSN 1076-7460) is published bimonthly (Jan., March, May, July, Sept., Nov.) by Le Jacq, a Blackwell Publishing imprint, located at Three Enterprise Drive, Suite 401, Shelton, CT 06484. Copyright 2007 by Le Jacq. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publishers. The opinions and ideas expressed in this publication are those of the authors and do not necessarily reflect those of the Editors or Publisher. For copies in excess of 25 or for commercial purposes, please contact Ben Harkinson at BHarkinson@bos.blackwellpublishing.com or 781-388-8511.

a somewhat understandable reluctance by physicians to add yet further medications to an already long list. The key to resolving some of these problems is to make the first step in hypertension treatment as effective as possible. This was certainly an important issue during the FDAs deliberations leading to its approval of first-line combination therapy. The data demonstrated in the paper by Cushman and colleagues3 provides further support to the concept of powerful and rapid treatment of hypertension. A large ongoing clinical trial in hypertension, in which all patients were initially treated with combination therapy, has reported in a preliminary paper the highest ever hypertension control rates achieved in a major randomized controlled trial.5 Since the primary reason for treating hypertension is to protect patients from fatal and nonfatal cardiovascular events, it is of particular importance to take note of studies in which rapid blood pressure control was associated with significantly reduced clinical event rates. In the Valsartan Antihypertensive Long-Term Use Evaluation (VALUE),6 regardless of which treatment patients were randomized to, those in whom blood pressure control was achieved (<140 mm Hg systolic) early in the study were significantly less likely than patients with uncontrolled blood pressure to experience stroke, cardiac events, and death. Of note, blood pressure responses by just 1 month of treatment initiation were predictive of clinical events across the full 5-year span of the study. Likewise, failure to achieve effective early blood pressure control in other major clinical trials could not be fully reversed despite the ongoing efforts of investigators.7,8 In all of these hypertension studies, the small but persistent blood pressure differences between treatments could be demonstrated to account for important differences in effects

on major clinical outcomes. Again, this provides strong support not only for getting blood pressure controlled effectively but for doing so as quickly as possible. In many patients, starting with combination therapy may be a large part of the answer. RefeRences
1 The Seventh Report of the Joint National Committee
on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289(19):25602572. Mancia G, DeBacker G, Dominiczak A, 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). J Hypertens. 2007;25(6):11051187. Cushman WC, Neutel JM, Saunders E, et al. Efficacy and safety of fixed combinations of Irbesartan/hydrochlorothiazide in older vs younger patients with hypertension uncontrolled with monotherapy. Am J Geriatr Cardiol. 2008;17:2736. Berlowitz DR, Ash AS, Hickey EC, et al. Inadequate management of blood pressure in a hypertensive population. N Engl J Med. 1998;339(27):19571963. Jamerson K, Bakris GL, Dahlof B, et al. Exceptional early blood pressure control rates: the ACCOMPLISH trial. Blood Press. 2007;16(2):8086. Weber MA, Julius S, Kjeldsen SE, et al. Blood pressure dependent and independent effects of antihypertensive treatment on clinical events in the VALUE Trial. Lancet. 2004;363(9426):20492051. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in highrisk hypertensive patients randomized to angiotensinconverting enzyme inhibitor or calcium channel blocker vs. diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288(23):29812997. Dahlof B, Sever PS, Poulter NR, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the AngloScandanavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomized controlled trial. Lancet. 2005;366(9489):895906.

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EDITORIAL

THE AMERICAN JOURNAL OF GERIATRIC CARDIOLOGY 2008 VOL. 17 NO. 1

The American Journal of Geriatric Cardiology (ISSN 1076-7460) is published bimonthly (Jan., March, May, July, Sept., Nov.) by Le Jacq, a Blackwell Publishing imprint, located at Three Enterprise Drive, Suite 401, Shelton, CT 06484. Copyright 2007 by Le Jacq. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publishers. The opinions and ideas expressed in this publication are those of the authors and do not necessarily reflect those of the Editors or Publisher. For copies in excess of 25 or for commercial purposes, please contact Ben Harkinson at BHarkinson@bos.blackwellpublishing.com or 781-388-8511.