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separate prescriptions or in fixed-dose combinations.129 (See figure 16.)
The initiation of therapy with more than one drug
increases the likelihood of achieving BP goal in a
more timely fashion. The use of multidrug combinations often produce greater BP reduction at lower
doses of the component agents, resulting in fewer
side effects.129,130
The use of fixed-dose combinations may be more
convenient and simplify the treatment regimen, and
may cost less than the individual components prescribed separately. Use of generic drugs should be
considered to reduce prescription costs, and the cost
of separate prescription of multiple drugs available
generically may be less than nongeneric, fixed-dose
combinations. The starting dose of most fixed-dose
combinations is usually below the doses used in
Figure 16. Algorithm for treatment of hypertension
LIFESTYLE MODIFICATIONS
Not at Goal Blood Pressure (<140/90 mmHg)
(<130/80 mmHg for those with diabetes or
chronic kidney disease)
Initial Drug Choices
Without Compelling
Indications
Stage 1
Hypertension
(SBP 140–159
or DBP 90–99 mmHg)
Thiazide-type diuretics
for most. May consider
ACEI, ARB, BB, CCB, or
combination
ACEI, angiotensin converting
enzyme inhibitor; ARB,
angiotensin receptor blocker;
BB, beta blocker; CCB, calcium
channel blocker; DBP, diastolic
blood pressure; SBP, systolic
blood pressure
With Compelling
Indications
Stage 2
Hypertension
(SBP >160 or DBP
>100 mmHg)
Two-drug combination for
most (usually thiazidetype diuretic and ACEI, or
ARB, or BB, or CCB)
Drug(s) for the
compelling indications
(see table 12)
Other antihypertensive
drugs (diuretics, ACEI,
ARB, BB, CCB) as needed
NOT AT GOAL
BLOOD PRESSURE
Optimize dosages or add additional drugs
until goal blood pressure is achieved.
Consider consultation with hypertension specialist.
Treatment
31
S p e c i a l S i t u at i o n s i n H y p e r t e n s i o n M a n a g e m e n t
Compelling Indications
Hypertension may exist in association with other
conditions in which there are compelling indications for use of a particular treatment based on
clinical trial data demonstrating benefits of such
therapy on the natural history of the associated
condition (table 12). Compelling indications for
specific therapy involve high-risk conditions that
can be direct sequelae of hypertension (HF, IHD,
chronic kidney disease, recurrent stroke) or commonly associated with hypertension (diabetes,
Table 12. Clinical trial and guideline basis for compelling indications for individual
drug classes
Compelling Indication*
ACEI
ARB
●
●
●
●
●
Postmyocardial infarction
Aldo ANT
BB
●
CCB
Diuretic
Heart failure
Clinical Trial Basis†
Recommended Drugs
●
ACC/AHA Heart Failure Guideline,132 MERITHF,133 COPERNICUS,134 CIBIS,135 SOLVD,136
AIRE,137 TRACE,138 ValHEFT,139 RALES,140
CHARM141
●
ACC/AHA Post-MI Guideline,142 BHAT,143
SAVE,144 Capricorn,145 EPHESUS146
High coronary disease risk
●
●
●
Diabetes
●
●
●
●
●
●
Chronic kidney disease
Recurrent stroke prevention
●
●
●
ALLHAT,109 HOPE,110 ANBP2,112 LIFE,102
CONVINCE,101 EUROPA,114 INVEST147
●
NKF-ADA Guideline,88,89 UKPDS,148 ALLHAT109
NKF Guideline,89 Captopril Trial,149
RENAAL,150 IDNT,151 REIN,152 AASK153
PROGRESS111
AASK, African American Study of Kidney Disease and Hypertension; ACC/AHA, American College of Cardiology/American
Heart Association; ACEI, angiotensin converting enzyme inhibitor; AIRE, Acute Infarction Ramipril Efficacy; Aldo ANT,
aldosterone antagonist; ALLHAT, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial; ANBP2,
Second Australian National Blood Pressure Study; ARB, angiotensin receptor blocker; BB, beta blocker; BHAT, ßBlocker Heart Attack Trial; Capricorn, Carvedilol Post-Infarct Survival Control in Left Ventricular Dysfunction; CCB, calcium channel blocker; CHARM, Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity; CIBIS,
Cardiac Insufficiency Bisoprolol Study; CONVINCE, Controlled Onset Verapamil Investigation of Cardiovascular End
Points; COPERNICUS, Carvedilol Prospective Randomized Cumulative Survival Study; EPHESUS, Eplerenone Post-Acute
Myocardial Infarction Heart Failure Efficacy and Survival Study; EUROPA, European Trial on Reduction of Cardiac Events
with Perindopril in Stable Coronary Artery Disease; HOPE, Heart Outcomes Prevention Evaluation Study; IDNT,
Irbesartan Diabetic Nephropathy Trial; INVEST, The International Verapamil-Trandolapril Study; LIFE, Losartan
Intervention for Endpoint Reduction in Hypertension Study; MERIT-HF, Metoprolol CR/XL Randomized Intervention Trial
in Congestive Heart Failure; NKF-ADA, National Kidney Foundation-American Diabetes Association; PROGRESS,
Peridopril Protection against Recurrent Stroke Study; RALES, Randomized Aldactone Evaluation Study; REIN, Ramipril
Efficacy in Nephropathy Study; RENAAL, Reduction of Endpoints in Non-Insulin Dependent Diabetes Mellitus with the
Angiotensin II Antagonist Losartan Study; SAVE, Survival and Ventricular Enlargement Study; SOLVD, Studies of Left
Ventricular Dysfunction; TRACE, Trandolapril Cardiac Evaluation Study; UKPDS, United Kingdom Prospective Diabetes
Study; ValHEFT, Valsartan Heart Failure Trial
*
Compelling indications for antihypertensive drugs are based on benefits from outcome studies or existing clinical
guidelines; the compelling indication is managed in parallel with the BP.
†
Conditions for which clinical trials demonstrate the benefit of specific classes of antihypertensive drugs used as part
of an antihypertensive regimen to achieve BP goal to test outcomes.
Special Situations in Hypertension Management
33