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810 PA R T V / Health Promotion and Disease Prevention

who were followed over a median of 4.1 years. With identical re- and the need to consider using a medication with dual functions
ductions in BP ( 26/12 mm Hg), the group treated with the but the question of whether it is the agent that is critical or the
ACE inhibitor had fewer cardiovascular events or deaths than the lowering of SBP still remains. As noted by Frohlich, clinicians
group treated with diuretics with a hazard ratio of 0.89 (95% con- must consider coexisting conditions of their patients, health care
fidence interval: 0.79 to 1.00). However, the primary endpoint for resources, and the fact that most persons with HTN will need at
benefit was restricted to men, and the final publication states that least two classes of medications to control BP . 160 Clinicians must
this observation needs to be interpreted with caution and requires also consider that only 37% of all hypertensive patients are at goal
confirmation. 158 Although these studies were well designed, there BP and greater titration, use of multiple agents, and attention to
were differences in designs, study populations, medications, and national guidelines may all support better HTN control. 38
endpoints.
Following the release of these two major trials, another study Treatment Based on JNC 7 Guidelines
in Europe, the Anglo-Scandanavian Cardiac Outcomes Trial— The current recommended guidelines from the JNC 7 provides an
Blood Pressure Lowering Arm (ASCOT–BPLA), was pub- algorithm for the management of pharmacotherapy in hyperten-
7
lished. 159 This trial was an open-label, controlled study of 19,257 sive individuals. As shown in Figure 35-1, on the basis of the
hypertensive patients who were 40 to 79 years of age, with 3 results of ALLHAT and other trials, the JNC 7 expert panel rec-
other cardiovascular risk factors. Patients received either amlodip- ommends that unless there are other compelling reasons, thiazide
ine or atenolol, titrated to maximum dose followed by perindopril diuretics should be the initial therapy in most persons with
with was added to amlodipine and bendroflumethiazide and HTN. 7,157 Compelling indications for the use of other classes of
potassium added to atenolol. If necessary, doxazosin was then antihypertensive medications in those patients with coexisting
added in both groups. The study was terminated at 5.5 years and medical conditions broaden the choice of agents used in the treat-
no significant difference was found in the primary endpoint of ment of patients with Stage 1 or 2 HTN. Table 35-5 includes the
nonfatal myocardial infarction and fatal coronary heart disease be- comorbid conditions that need to be considered when selecting
tween those patients receiving amlodipine and those receiving medications for the person with HTN. In persons with Stage 2
atenolol (8.2 vs. 9.1 per 1,000 P 0.105). 159 Secondary end- HTN ( 160 mm Hg SBP or 100 mm Hg DBP) two medica-
points were better for the amlodipine group including total coro- tions are recommended for initial treatment with a thiazide di-
nary endpoints, total cardiovascular procedures, cardiovascular uretic recommended as the choice of one of these agents. Other
mortality, stroke, peripheral arterial disease, and the development factors that need to be considered when prescribing antihyperten-
of diabetes. However, it has also been noted that in the amlodipine sive treatment include the cost, formulary, duration of action, fre-
group both SBP and DBP demonstrated significant reductions, quency of adverse effects, patient preference, adherence, quality of
which may have been the contributing factor for better patient life, and other medications the patient is using including over-the-
outcomes. What is notable from this study is that those patients counter agents that may be used for other conditions.
treated in the amlodipine group had a reduction in cardiovascular Seven classes of medications are available in the treatment of
events beginning as early as 1 month following treatment, again HTN including (1) diuretics; (2) adrenergic inhibitors including
likely due to the greater decline in BP. -blocking agents, central-acting inhibitors, central -agonists,
Since the ALLHAT, ANBP2, and ASCOT studies were done, -adrenergic blockers, and combined -adrenergic and -adren-
there have been many other trials looking at the value of the five ergic blockers; (3) vasodilators; (4) calcium channel blockers; (5)
major classes of medications to treat HTN. Clearly, there may be ACE inhibitors; (6) angiotensin II receptor blockers; and (7)
beneficial effects from various agents in certain subpopulations ARBs. Table 35-6 lists the generic and trade names, usual doses,

Table 35-5 ■ CLINICAL TRIAL AND GUIDELINE BASIS FOR COMPELLING INDICATIONS FOR INDIVIDUAL DRUG CLASSES
Recommended Drugs †
Compelling Indication* Diuretic BB ACEI ARB CCB ALDO ANT Clinical Trial Basis ‡,§
Heart failure • • • • • ACC/AHA Heart Failure Guideline, 161
MERIT-HF, 162 COPERNICUS, 163 CIBIS, 164
SOLVD, 165 AIRE, 166 TRACE, 167 ValHEFT, 168
RALES 169
Post-MI • • • ACC/AHA Post-MI Guideline, 170 BHAT, 171
SAVE, 172 Capricorn, 173 EPHESUS 174
High coronary disease risk • • • • ALLHAT, 157 HOPE, 175 ANBP 2, 158 LIFE, 176
CONVINCE 177
Diabetes • • • • • NKF-ADA Guideline, 178 UKPDS, 179 ALLHAT 157
Chronic kidney disease • • NKF Guideline, 178 Captopril Trial, 180 RENAAL, 181
IDNT, 182 REIN, 183 AASK 184
Recurrent stroke prevention • • PROGRESS 185

*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.
†
Drug abbreviations: ACEI, angiotensin-converting enzyme inhibitor; Aldo ANT, aldosterone antagonist; BB, -blocker; CCB, calcium channel blocker.
‡
Conditions for which clinical trials demonstrate benefit of specific classes of antihypertensive drugs.
§
See list of references.
From Chobanian, A. V., Bakris, G. L., Black, H. R., et al. (2003). The Seventh Report of the Joint National committee on Prevention, Detection, Evaluation, and Treatment of High
Blood Pressure: The JNC 7 report. JAMA, 289(19), 2560–2572. (Erratum in JAMA, 2003, 290[2], 197.)