Page 236 - Basic _ Clinical Pharmacology ( PDFDrive )

222 SECTION III Cardiovascular-Renal Drugs

TABLE 13–4 Differences between systolic and dilation and thus slow the downward spiral of heart failure.
diastolic heart failure. Consequently, ACE inhibitors are beneficial in all subsets of
patients—from those who are asymptomatic to those in severe
Variable or Diastolic Heart chronic failure. This benefit appears to be a class effect; that is, all
Therapy Systolic Heart Failure Failure
ACE inhibitors appear to be effective.
Cardiac output Decreased Decreased The angiotensin II AT receptor blockers (ARBs, eg, losartan)
1
Ejection fraction Decreased Normal produce beneficial hemodynamic effects similar to those of ACE
Diuretics ↓ Symptoms; first-line Use with caution 1 inhibitors. However, large clinical trials suggest that when used
therapy if edema present alone, ARBs are best reserved for patients who cannot toler-
ate ACE inhibitors (usually because of cough). In contrast, the
ACEIs ↓ Mortality in chronic HF May help to ↓ LVH
ARB valsartan combined with the neprilysin inhibitor sacubitril
ARBs ↓ Mortality in chronic HF May be beneficial
(Entresto) has additional benefit in HFrEF and is recommended
ARNI ↓ Symptoms and ↓ Symptoms and in 2016 guidelines.
NT-proBNP NT-proBNP
Aldosterone ↓ Mortality in chronic HF May be useful
inhibitors VASODILATORS
2
Beta blockers , Beta blocker ↓ mortality Useful to ↓ HR,
ivabradine in chronic HF, ivabradine ↓ BP Vasodilator drugs can be divided into selective arteriolar dilators,
reduces hospitalizations
Calcium channel No or small benefit 3 Useful to ↓ HR, venous dilators, and drugs with nonselective vasodilating effects.
The choice of agent should be based on the patient’s signs and
blockers ↓ BP
symptoms and hemodynamic measurements. Thus, in patients
Digoxin May reduce symptoms Little or no role with high filling pressures in whom the principal symptom is
Nitrates May be useful in acute HF 4 Use with caution 1 dyspnea, venous dilators such as long-acting nitrates will be most
PDE inhibitors May be useful in acute HF Very small study helpful in reducing filling pressures and the symptoms of pulmo-
in chronic HF was nary congestion. In patients in whom fatigue due to low left ven-
positive
tricular output is a primary symptom, an arteriolar dilator such as
Positive ↓ Symptoms, Not recommended hydralazine may be helpful in increasing forward cardiac output.
inotropes hospitalizations
In most patients with severe chronic failure that responds poorly
1
Avoid excessive reduction of filling pressures. to other therapy, the problem usually involves both elevated filling
2 Limited to certain β blockers (see text).
3 pressures and reduced cardiac output. In these circumstances, dila-
Benefit, if any, may be due to BP reduction.
4 Useful combined with hydralazine in selected patients, especially African Americans. tion of both arterioles and veins is required. A fixed combination
ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; of hydralazine and isosorbide dinitrate is available as isosorbide
ARNI, angiotensin receptor inhibitor plus neprilysin inhibitor; BP, blood pressure; HF, dinitrate/hydralazine (BiDil), and this is currently recommended
heart failure; HR, heart rate; LVH, left ventricular hypertrophy; NT-proBNP, N-terminal for use in African Americans.
pro-brain natriuretic peptide; PDE, phosphodiesterase.
particularly hazardous if the patient is to be given digitalis. Hypo- BETA BLOCKERS & ION CHANNEL
kalemia can be treated with potassium supplementation or through
the addition of an ACE inhibitor or a potassium-sparing diuretic BLOCKERS
such as spironolactone. Spironolactone or eplerenone should prob-
ably be considered in all patients with moderate or severe heart Beta blocker therapy in patients with heart failure is based on the
failure, since both appear to reduce both morbidity and mortality. hypothesis that excessive tachycardia and adverse effects of high
catecholamine levels on the heart contribute to the downward
course of heart failure. The results of clinical trials clearly indicate
ACE INHIBITORS & ANGIOTENSIN that such therapy is beneficial if initiated cautiously at low doses,
RECEPTOR BLOCKERS even though acutely blocking the supportive effects of catechol-
amines can worsen heart failure. Several months of therapy may
In patients with left ventricular dysfunction but no edema, an be required before improvement is noted; this usually consists of a
ACE inhibitor should be the first drug used. Several large stud- slight rise in ejection fraction, slower heart rate, and reduction in
ies have shown clearly that ACE inhibitors are superior to both symptoms. As noted above, not all β blockers have proved useful,
placebo and to vasodilators and must be considered, along with but bisoprolol, carvedilol, metoprolol, and nebivolol have been
diuretics, as first-line therapy for chronic heart failure. However, shown to reduce mortality.
ACE inhibitors cannot replace digoxin in patients already receiv- In contrast, the calcium-blocking drugs appear to have no role in
ing the glycoside because patients withdrawn from digoxin dete- the treatment of patients with heart failure. Their depressant effects
riorate while on ACE inhibitor therapy. on the heart may worsen heart failure. On the other hand, slowing
By reducing preload and afterload in asymptomatic patients, of heart rate with ivabradine (an I blocker, see Chapter 12) may
f
ACE inhibitors (eg, enalapril) slow the progress of ventricular be of benefit.