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Sacubitril⁄Valsartan and Ivabradine: Promising Drugs for Severe Heart Failure

Sacubitril/Valsartan and Ivabradine: Promising Drugs for Severe Heart Failure

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  • Sacubitril/valsartan 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.

The 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. Information regarding these drugs was published in an article in the US Pharmacist.

Sacubitril/valsartan, a 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.


Valsartan, a 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.

Sacubitril acts 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 heart.

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 failure.

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 blocker. 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 medication.

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.

About Heart Failure

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.

Reference :
  1. Sarbacker GB, Wilder AG, Heart Failure Guidelines: Introduction to the New Agents. US Pharm. 2018; 43(2):22-26.
Source: Medindia

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