A Textbook of Clinical Pharmacology and Therapeutics

The drugs that are most effective in prolonging survival in
chronic heart failure work indirectly, by reducing preload,
afterload or heart rate, rather than directly by increasing the
force of contraction.

THERAPEUTIC OBJECTIVES AND GENERAL

MEASURES FOR CHRONIC HEART FAILURE

Therapeutic objectives in treating heart failure are

• to improve symptoms and


• to prolong survival.

General principles of treating heart failure:

• restrict dietary salt;


• if there is hyponatraemia, restrict fluid;


• review prescribed drugs and if possible withdraw drugs
  that aggravate cardiac failure:
  
  
  • some negative inotropes (e.g. verapamil)
  
  
  • cardiac toxins (e.g. daunorubicin,ethanol,imatinib,
    gefitinib,trastuzumab)
  
  
  • drugs that cause salt retention (e.g. NSAID).
  
  
  
  


• consider anticoagulation on an individual basis.

DRUGS FOR HEART FAILURE

DIURETICS

For more information, see Chapter 28 for use of diuretics in
hypertension and Chapter 36, for mechanisms, adverse effects
and pharmacokinetics.

Use in heart failure

Chronic heart failure: a diuretic is used to control symptomatic
oedema and dyspnoea in patients with heart failure. A thiazide
(see Chapters 28 and 36) may be adequate in very mild cases,
but a loop diuretic (e.g. furosemide) is usually needed. Unlike
several of the drugs described below, there has been no ran-
domized controlled trial investigating the influence of loop
diuretics on survival in heart failure, but the other treatments
were added to a loop diuretic and this is usually the starting
point of drug treatment. Spironolactoneimproves survival in
patients with cardiac failure and counters diuretic-induced
hypokalaemia. Diuretic-induced hypokalaemia increases
the toxicity of digoxin. Conversely, spironolactoneand other
K-retaining diuretics (e.g. amiloride,triamterene) can cause
severe hyperkalaemia, especially if given with ACEI or sartans
(see below) to patients with renal impairment. It is therefore
important to monitor plasma Kduring treatment with all
diuretic therapy.
Acute heart failure: acute pulmonary oedema is treated by sit-
ting the patient upright, administering oxygen (FiO 2 , 28–40%)
and intravenous furosemidewhich is often effective within a
matter of minutes. Intravenous morphine(Chapter 25) is also
useful. A slow intravenous infusion of furosemideby syringe
pump may be useful in resistant cases. Once the acute situation

has resolved the situation is re-assessed and drugs used for

chronic heart failure (see below), including oral diuretics, are

usually indicated.

ANGIOTENSIN-CONVERTING ENZYME INHIBITORS

For the mechanism of action and other aspects of angiotensin-

converting enzyme inhibitors, see Chapter 28.

Use in heart failure

The first approach shown to reduce mortality in heart failure

was combined hydralazineandnitratetherapy (see below).

Soon after, an angiotensin-converting enzyme inhibitor (ACEI)

(captopril) was shown to do better. Other ACEI were also

shown to improve survival and ACEI treatment for heart fail-

ure was rapidly adopted. When symptoms are mild, diuretics

can be temporarily discontinued a day or two before starting

an ACEI, reducing the likelihood of first-dose hypotension.

In these circumstances, treatment with an ACE inhibitor can be

started as an out-patient, as for hypertension (see Chapter 28).

A small starting dose is used and the first dose is taken last

thing before retiring at night, with advice to sit on the side of

the bed before standing if the patient needs to get up in the

night. The dose is gradually increased to one that improves

symptoms (and survival) with careful monitoring of blood

pressure. Serum potassium and creatinine are checked after

one to two weeks. Hypotension is more of a problem when

starting treatment in heart failure patients than when treating

hypertension, especially with short-acting drugs (e.g. capto-

pril). Not only is the blood pressure lower to start with, but

concentrations of circulating renin are high and increased fur-

ther by diuretics. ACEI cause ‘first-dose’ hypotension most

severely in patients with the greatest activation of the

renin–angiotensin system. These are consequently those most

likely to benefit from an ACEI in the long term. Long-acting

drugs (e.g. ramipril, trandolapril) cause less first-dose

hypotension and can be given once daily. ACEI are usually

well tolerated during chronic treatment, although dry cough

is common and occasionally unacceptable (see Chapter 28 for

other adverse effects). Important drug–drug interactions can

occur with NSAIDs (Chapter 26), which may cause renal

failure and severe hyperkalaemia, especially in heart failure

patients treated with ACEI.

ANGIOTENSIC RECEPTOR ANTAGONISTS, SARTANS

See Chapter 28 for the mechanism of action.

Use in heart failure

As in hypertension, the pharmacodynamics of sartans are similar

to those of ACEI apart from a lower incidence of some adverse

effects, including, particularly, dry cough. Several of these

drugs (e.g. candesartan,valsartan) have been shown to pro-

long life in randomized controlled trials, the magnitude of the

effect being similar to ACEI. It is possible that they have some

additive effect when combined with ACEI, but this is hard to

prove at doses that are not supramaximal. Because of the

greater experience with ACEI and the lower cost, many physi-

cians prefer to use an ACEI, unless this is not tolerated.

DRUGS FORHEARTFAILURE 213