availability of the sacubitril/valsartan combination and ivabradine for the
treatment of heart failure has prompted three large cardiac organizations, the
American College of Cardiology, the American Heart Association, and the Heart
Failure Society of America to publish updated guidelines regarding their use in
heart failure patients
and ivabradine are drugs that help in the treatment of severe heart
failure through different mechanisms.
- They reduce the
need for hospitalizations due to heart failure
- They have been
included by international cardiovascular organization in the guidelines
for the treatment of severe heart failure.
. Information regarding these drugs was
published in an article in the US
combination of two cardiac drugs, was approved by the US FDA for the treatment
of symptomatic heart failure with systolic dysfunction. Systolic dysfunction is when the heart is
unable to contract with enough force, and is therefore unable to pump blood to
the rest of the body efficiently.
‘Sacubitril/valsartan and ivabradine have been recently approved by the US FDA for the treatment of severe heart failure, and have been included in the latest guidelines by leading cardiac organizations for the treatment of heart failure.’
drug that was available earlier, is an
angiotensin II receptor blocker (ARB), and prevents the release of aldosterone
It relaxes blood vessels and helps in excretion of salt and water. Thus, it
reduces the work load of the heart and improves the symptoms of heart failure.
by a different mechanism. It prevents
the breakdown of natriuretic peptides by inhibiting an enzyme called neprilysin
Natriuretic peptides are substances that are naturally released by the body
during heart failure and relax blood vessels and excrete salt and water. Thus,
Sacubitril adds to the effect of valsartan in reducing the work load of the
The combination should
not be used in patients who had previously experienced angioedema (severe
swelling) while taking an angiotensin converting enzyme (ACE) inhibitor or ARB,
or due to any other cause. It should not be used along with aliskiren in
patients with diabetes or an ACE inhibitor (ACE inhibitors should be stopped at
least 36 hours before starting this combination). Adverse effects include low
blood pressure, high blood potassium levels, cough, dizziness and kidney
The beneficial effect of
the combination was demonstrated in the PARADIGM-HF trial, which compared it to
enalapril, an ACE inhibitor, in patients with an ejection fraction of less than
40% and a B-type natriuretic peptide level of between 100 and 150 pg/ml. The
combination significantly reduced deaths due to cardiovascular causes and
hospitalization due to heart failure. It also reduced the symptoms and physical
limitations in patients due to heart failure.
The second drug
discussed in the article was ivabradine. Ivabradine
was approved by the US FDA in 2015 for patients with left ventricular heart
failure with an ejection fraction of 35% or less, with a normal heart rate and
rhythm, and are either on a maximum dose of beta blocker or cannot use a beta
. It acts on the sinoatrial node, the natural pacemaker of the
heart, and slows down the heart. It should not be used in acute decompensated
heart failure (sudden worsening of heart failure), severe liver dysfunction, in
patients with an artificial cardiac pacemaker, a blood pressure <90/50 mmHg
or a resting heart rate of less than 60 beats per minute. Some patients suffer
from visual problems, which usually resolve with time, or after stopping the
The benefit of
ivabradine in the treatment of moderate-to-severe HF and LV systolic
dysfunction heart failure was demonstrated in the SHIFT (Systolic Heart Failure
Treatment with the If Inhibitor Ivabradine Trial) trial. It reduced the
hospital admission for worsening heart failure symptoms as compared to placebo.
The heart acts as a pump
whose continuous and rhythmic contractions and relaxations pump the blood
throughout the body. A failure of the heart to carry out this function results
in heart failure. Heart failure
is classified at right-sided failure, when
the right side of the heart is affected, and left-sided failure when the left
side of the heart is affected. Left-sided heart failure or left ventricular
dysfunction can be systolic dysfunction, where the contraction of the heart is
affected, or diastolic dysfunction, where the heart fails to relax and thereby
fill up properly. Patients with systolic dysfunction have reduced ejection
fraction, while the ejection fraction is normal in those with diastolic
dysfunction. The ejection fraction refers to the percentage of blood that is
pumped out of the left side of the heart during its contraction. The normal
ejection fraction is 55% or more.
Heart failure patients
suffer from symptoms of breathlessness, swelling of feet and fatigue. The
structural classification of heart failure by the ACCF and the AHA classifies
heart failure into 4 types (A to D), while the functional heart failure
classification by the New York Heart Association (NYHA) classifies it as I-IV.
- Sarbacker GB, Wilder AG, Heart Failure Guidelines: Introduction to the New Agents.
US Pharm. 2018; 43(2):22-26.