QUESTION 1: T.J. is a 58-year-old man with a 10-year
mg daily for more than 2 years, and his BP has been well
controlled during this time. His BP at an office visit today
317Essential Hypertension Chapter 14
but he is a smoker. T.J. also has dyslipidemia, which is well
controlled with simvastatin 40 mg daily. His Framingham
risk score is 15%, and he denies dizziness or difficulties with
his medications. Should T.J.’s antihypertensive therapy be
changed to reduce his medication doses or possibly discontinue some of his medications?
or months after discontinuation of their medications. This is
called step-down therapy. However, it is not a feasible option for
most patients with hypertension. Primary prevention patients
step-down therapy. This option should not be considered for
patients with other major CV risk factors, a Framingham risk
or large dosage reductions should be avoided because of the risk
of rapid return of uncontrolled BP and even rebound surges in BP
(as is seen with rapid withdrawal of a β-blocker or an α2-agonist).
Step-down therapy is most often plausible for patients who
have lost significant amounts of weight or have drastically
changed their lifestyle. Any attempt at step-down therapy must
be accompanied by scheduled follow-up evaluations because
BP values can rise over the course of months to years after
drug discontinuation, especially if lifestyle modifications are not
maintained. With adherence to lifestyle modifications (weight
loss, reduction in sodium and alcohol), nearly 70% of patients
remained free of antihypertensives for up to 1 year after being
withdrawn from thiazide-based therapy in the Hypertension
Step-down therapy in T.J. is not an option. Although he does
Framingham risk score that is greater than or equal to 10%.
QUESTION 1: A.R. is a 49-year-old black woman with type
2 diabetes. She started lisinopril 10 mg daily 2 weeks ago
weekly BP measurements, and her values have averaged
when repeated), and her heart rate is 78 beats/minute. She
ratio is 80 mg/g (2 weeks ago it was 90 mg/g). Is 2 weeks of
lisinopril therapy long enough to assess her antihypertensive response?
Several ACEIs are available (Table 14-12). Most ACEIs are
dosed once daily in hypertension (Table 14-12). In general, most
ACEIs, if used in equivalent doses, are considered interchangeable.
Angiotensin-Converting Enzyme Inhibitors in Hypertension
Usual Starting Usual Dosage Dosing
Drug Dose (mg/d)a Range (mg/d) Frequency
Benazepril 10 20–40 Daily to BID
Captopril 25 50–100 BID to TID
Enalapril 5 10–40 Daily to BID
Moexipril 7.5 7.5–30 Daily to BID
Quinapril 10 20–80 Daily to BID
Ramipril 2.5 2.5–20 Daily to BID
a Starting dose may be decreased 50% if patient is volume depleted, in acute
heart failure exacerbation, or very elderly (≥75 year).
BID, twice daily; TID, three times daily.
The time to reach steady-state BP conditions is similar to what
is seen with other antihypertensive agents. It may take several
weeks before the full antihypertensive effects of ACEIs are seen.
Therefore, evaluating BP response 2 to 4 weeks after starting
or changing the dose of an ACEI is appropriate. A.R. has been
taking lisinopril for 2 weeks, and her present BP should be used
to determine whether she has attained goal. Both her BP range
during the past few weeks and today’s average BP are above her
goal of less than 130/80 mm Hg (because she has diabetes).
CASE 14-6, QUESTION 2: Why should A.R. have serum
potassium and serum creatinine monitored while on lisinopril therapy?
Serum potassium can increase with ACEI therapy as a
result of aldosterone reduction. Potassium increases with ACEI
monotherapy are small (typically 0.1 to 0.2 mEq/L) and usually
do not cause hyperkalemia. This risk is increased when ACEIs are
used in patients with significant CKD (GFR<60 mL/minute/1.73
m2), or when they are used in combination with other drugs that
in the kidney. This results in a minor decrease in GFR that may
in serum creatinine. Increases in serum creatinine of up to 30%
from the baseline creatinine value are safe and anticipated. In
these patients, the ACEI should be continued because a strong
association exists between acute increases in serum creatinine of
with an increase in serum creatinine of greater than 30% should
have their ACEI therapy temporarily discontinued, as this may
indicate other medical problems. Some of these problems can be
underlying renal disease (such as bilateral renal artery stenosis) or
other situations that may be compromising renal blood flow (e.g.,
volume depletion, concomitant nonsteroidal anti-inflammatory
to 4 weeks after starting ACEI therapy or increasing the dose.
CASE 14-6, QUESTION 3: A.R.’s lisinopril dose is increased
to 20 mg daily. Will this doubling of her dose place her at
risk for significant hypotension?
318 Section 2 Cardiac and Vascular Disorders
The very elderly, patients with volume depletion, or patients
hypotension, dizziness, or syncope. The increased pretreatment
activity of the RAAS, coupled with blockade of this system,
explains this effect. These patients should initiate ACEI therapy
at half the normal dose (Table 14-12), followed by slow titration
Concurrent diuretic therapy may predispose some patients to
first-dose hypotension. When ACEIs were first approved, dosing
guidelines recommended starting at half the standard dose of the
ACEI, decreasing the dose of the diuretic, or stopping the diuretic
before initiating the ACEI. This was owing to fear that BP would
sharply and acutely drop. These dosing recommendations are
not necessary unless the patient is hemodynamically unstable
(volume depleted, hyponatremic, or poorly compensated heart
CASE 14-6, QUESTION 4: Is an ACEI an effective therapy in
ACEI monotherapy is generally more effective at lowering
BP in white patients than in black or elderly patients. Elderly and
black patients are more likely to have low renin hypertension,
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