Hypertension Journal

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Current Use of Diuretics in the Managementof Hypertension
  JOHTN
COMMENTARY
Current Use of Diuretics in the Management
of Hypertension
Aram V Chobanian
Professor
School of Medicine, Boston University, Boston, MassachusettsUSA
Correspondence Author: Aram V Chobanian, Professor, Schoolof Medicine, Boston University, Boston, Massachusetts, USA
e-mail: achob@bu.edu
 
ABSTRACT
No single class of antihypertensive drugs has hadas much impact on the treatment of hypertension asdiuretics. The introduction in the late 1950s of chlorothiazideand its analogues revolutionized the treatmentof hypertension. Working then as a research fellowin hypertension with Dr Robert Wilkins at BostonUniversity, I observed firsthand the effects of this newtherapy that dramatically changed our ability to controlhypertension. The availability of these effective and welltolerateddrugs led to placebo-controlled trials, such asthe Veterans Administration Cooperative Trials and theSystolic Hypertension in the Elderly Program (SHEP)study, which demonstrated the benefits of blood pressurelowering in individuals with severe and mild forms ofhypertension and those with isolated systolic hypertension.Despite the passage of almost 60 years, diureticshave remained important in managing hypertensionwhen used either alone or in combination with otherantihypertensive agents.
How to cite this article: Chobanian AV. Current Use ofDiuretics in the Management of Hypertension. Hypertens J2016;2(4):181-182.
Source of support: Nil
Conflict of interest: None
 
 

INTRODUCTION

No single class of antihypertensive drugs has hadas much impact on the treatment of hypertension asdiuretics. The introduction in the late 1950s of chlorothiazideand its analogues revolutionized the treatmentof hypertension. Working then as a research fellowin hypertension with Dr Robert Wilkins at BostonUniversity, I observed firsthand the effects of this newtherapy that dramatically changed our ability to controlhypertension. The availability of these effective and welltolerateddrugs led to placebo-controlled trials, such asthe Veterans Administration Cooperative Trials and theSystolic Hypertension in the Elderly Program (SHEP)study, which demonstrated the benefits of blood pressurelowering in individuals with severe and mild forms ofhypertension and those with isolated systolic hypertension.Despite the passage of almost 60 years, diureticshave remained important in managing hypertensionwhen used either alone or in combination with otherantihypertensive agents.

A controversy has developed in the past few yearsas to whether the effects of thiazides and thiazide-typediuretics as chlorthalidone and indapamide are alikein the management of hypertension. In this editionof the Hypertension Journal, Dr Anil Pareek and hisassociates have addressed the issue and have provideda comprehensive review that includes their own recentclinical data to support the preferential use of chlorthalidonerather than hydrochlorothiazide in hypertension.Despite its early approval for the treatment of hypertension,which came soon after that of hydrochlorothiazide chlorthalidone has had relatively minimal use since then,probably because of its early reputation of causing morehypokalemia and other metabolic abnormalities than thethiazides. However, in retrospect, such a reputation wasgarnered because of the high doses of chlorthalidoneused initially which averaged more than 50 mg per day,or more than eight times that employed in the studiesof Pareek and associates. Clinicians have continuedto shy away from using chlorthalidone even after itwas selected at lower doses to be the diuretic of choicein three major National Institutes of Health-fundedhypertension trials - the SHEP, Antihypertensive andLipid-Lowering Treatment to Prevent Heart Attack Trial(ALLHAT), and Systolic Blood Pressure InterventionTrial (SPRINT) studies.

 
The pharmacokinetic profile of chlorthalidone clearlydiffers from that of hydrochlorothiazide. Importantly,chlorthalidone has a much longer duration of antihypertensiveeffect than that of hydrochlorothiazideand is more potent at comparable dosages. When used insmall doses (e.g., 12.5 mg per day), hydrochlorothiazidemay not provide a full 24-hour effect on blood pressurein some patients in contrast to the long action of chlorthalidone,although these differences may be overcomeif larger doses of hydrochlorothiazide are employed.Whether other clinically important differences existbetween the two drugs is uncertain despite variousspeculations to that effect.

The review provided by Pareek et al shows that theantihypertensive effect of chlorthalidone at 6.25 mg perday is not significantly different from that of selectedrepresentatives of other antihypertensive drug classeswhen used in various combinations. In addition, themetabolic side effects of chlorthalidone at this doseare minimal. Other published data have indicated thatchlorthalidone is useful in most hypertensive individuals,including diabetics. Based on the availableevidence, I would conclude that chlorthalidone shouldbe preferred over hydrochlorothiazide in the treatmentof hypertension.

Combination therapy is particularly important inhypertension since in more than one-half of individuals,two or more antihypertensive drugs are required tocontrol the blood pressure to less than 140/90 mm Hg.Combination preparations that involve two or three
Hypertension Journal, October-December, Vol 2, 2016 181

Aram V Chobanian

antihypertensive drugs are of practical value in reducingcost and improving adherence to therapy. Despite thedemonstrated efficacy of blood pressure lowering inreducing mortality and morbidity from cardiovascularand renal diseases irrespective of age, gender, race,ethnicity, socioeconomic status, or the presence or
 
absence of cardiovascular disease, less than one-thirdof hypertensive persons worldwide have their bloodpressure controlled to less than 140/90 mm Hg. With aprevalence of more than 1.2 billion persons worldwide,hypertension remains a serious public health problem thatdemands intensive efforts in every country for its control.
 
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