Page 235 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 13 Drugs Used in Heart Failure 221

BETA-ADRENOCEPTOR BLOCKERS because of other disease but have no signs or symptoms of heart
failure. Stage B patients have evidence of structural heart disease
Most patients with chronic heart failure respond favorably to but no symptoms of heart failure. Stage C patients have structural
certain β blockers despite the fact that these drugs can precipi- heart disease and symptoms of failure, and symptoms are respon-
tate acute decompensation of cardiac function (see Chapter 10). sive to ordinary therapy. Patients in stage C must often be hospi-
Studies with bisoprolol, carvedilol, metoprolol, and nebivolol talized for acute decompensation, and after discharge, they often
showed a reduction in mortality in patients with stable severe decompensate again, requiring rehospitalization. Stage D patients
heart failure, but this effect was not observed with another have heart failure refractory to ordinary therapy, and special inter-
β blocker, bucindolol. A full understanding of the beneficial ventions (eg, resynchronization therapy, transplant) are required.
action of β blockade is lacking, but suggested mechanisms include Once stage C is reached, the severity of heart failure is usually
attenuation of the adverse effects of high concentrations of cat- described according to a scale devised by the New York Heart
echolamines (including apoptosis), up-regulation of β receptors, Association. Class I failure is associated with no limitations on
decreased heart rate, and reduced remodeling through inhibition ordinary activities and symptoms that occur only with greater
of the mitogenic activity of catecholamines. than ordinary exercise. Class II failure is characterized by slight
limitation of activities and results in fatigue and palpitations with
ordinary physical activity. Class III failure results in fatigue, short-
OTHER DRUGS ness of breath, and tachycardia with less than ordinary physical

activity, but no symptoms at rest. Class IV failure is associated
Neuroregulatory proteins appear to have cardiac and neural effects. with symptoms even when the patient is at rest.
The neuregulin GGF2 protein (cimaglermin) has been shown to
benefit cardiac function in several animal models of heart failure.
Drugs used in type 2 diabetes have been of concern because of the MANAGEMENT OF CHRONIC HEART
association of this condition with cardiac events. Therefore, it is FAILURE
of interest that some of these agents appear to benefit patients with
both heart failure and type 2 diabetes. Liraglutide, a GLP-1 ago- The major steps in the management of patients with chronic
nist (see Chapter 41), has been shown in some studies to nonsig- heart failure are outlined in Tables 13–3 and 13–4. Updates to
nificantly reduce deaths from cardiovascular causes as well as the the ACC/AHA guidelines suggest that treatment of patients at
rates of myocardial infarction, nonfatal stroke, and hospitalization high risk (stages A and B) should be focused on control of hyper-
for heart failure. Empagliflozin, an SGLT2 inhibitor, has also tension, arrhythmias, hyperlipidemia, and diabetes, if present.
been shown to reduce hospitalizations for heart failure. Once symptoms and signs of failure are present, stage C has been
entered, and active treatment of failure must be initiated.

■ CLINICAL PHARMACOLOGY OF SODIUM REMOVAL
DRUGS USED IN HEART FAILURE
Sodium removal—by dietary salt restriction and a diuretic—is the
Detailed guidelines are issued by US and European expert groups mainstay in management of symptomatic heart failure, especially
(see References). The American College of Cardiology/American if edema is present. The use of diuretics is discussed in greater
Heart Association (ACC/AHA) guidelines for management of detail in Chapter 15. In very mild failure, a thiazide diuretic
chronic heart failure specify four stages in the development of may be tried, but a loop agent such as furosemide is usually
heart failure (Table 13–3). Patients in stage A are at high risk required. Sodium loss causes secondary loss of potassium, which is

TABLE 13–3 Classification and treatment of chronic heart failure.

ACC/AHA Stage 1 NYHA Class 2 Description Management
A Prefailure No symptoms but risk factors present 3 Treat obesity, hypertension, diabetes, hyperlipidemia, etc
B I Symptoms with severe exercise ACEI/ARB, β blocker, diuretic
C II/III Symptoms with marked (class II) or mild Add aldosterone antagonist, digoxin; CRT, ARNI, hydralazine/
(class III) exercise nitrate 4
D IV Severe symptoms at rest Transplant, LVAD
1 American College of Cardiology/American Heart Association classification.
2
New York Heart Association classification.
3 Risk factors include hypertension, myocardial infarct, diabetes.
4
For selected populations, eg, African Americans.
ACC, American College of Cardiology; ACEI, angiotensin-converting enzyme inhibitor; AHA, American Heart Association; ARB, angiotensin receptor blocker; ARNI, angiotensin
receptor inhibitor plus neprilysin inhibitor; CRT, cardiac resynchronization therapy; LVAD, left ventricular assist device; NYHA, New York Heart Association.