#10 Drugs for Heart Failure with Preserved Ejection Fraction

Overview

Your heart is full of incredible muscles. Pumping 24/7 to move oxygenated blood to organs and tissues, the heart takes no days off. But with 4 chambers and 4 major valves, the heart is prone to an array of diseases and conditions that can affect its function. Heart failure – the condition in which the left ventricle chamber’s ability to pump blood from the heart to the body is reduced – is common and has multiple subtypes.

Heart failure with preserved ejection fraction (HFpEF) – also known as diastolic heart failure – occurs when the heart muscles contract normally, but the left ventricle muscles are thickened, and fail to relax as they should. With preserved ejection fraction, the left ventricle is unable to properly fill with oxygenated blood. With less blood in the chamber during relaxation, there is less blood available to distribute to the body when the ventricle contracts. Common complaints with HFpEF are similar to those of heart failure with reduced ejection fraction (or systolic heart failure); namely, difficult/labored breathing, fatigue and exercise intolerance or lack of energy. HFpEF occurs in nearly 50% of all heart failure cases, and prevalence is growing due to longer life, hypertension, diabetes, obesity, coronary artery disease, hyperlipidemia and other cardiac conditions.  

In treatment for the aforementioned heart failure with reduced ejection fraction, mortality benefit is seen with many medication classes, including an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, angiotensin receptor neprilysin inhibitor, beta blocker, mineralocorticoid receptor antagonist and other medications. But for individuals with heart failure with preserved ejection fraction – the condition in question – current recommendations for treatment are directed at relieving symptoms and targeting co-morbid conditions. Patients with HFpEF may be prescribed similar medications used in heart failure with reduced ejection fraction, including diuretics to relieve excess fluid buildup, but do not experience the clinical outcomes achieved in heart failure with reduced ejection fraction. Currently, 2 classes of medications, an SGLT2 inhibitor and an angiotensin receptor neprilysin inhibitor, are being explored in HFpEF.

Sodium glucose co-transporter 2 (SGLT2) inhibitors are a class of medications that inhibit the reabsorption of glucose in the kidneys – thereby lowering blood sugar. Due to their significant effect on blood glucose, SGLT2 inhibitors are used in the treatment of type II diabetes. SGLT2 inhibitors made their debut in the cardiac space nearly four years ago, with the results of a few high-profile trials showing not only SGLT2 inhibitor safety in patients with type II diabetes, but a reduced risk of cardiovascular death and heart failure hospitalization. Since the release of research findings, several SGLT2 drugs have recieved, or are in the process of receiving, FDA approval for reduced risk of cardiovascular death and HF hospitalization in adults with type II diabetes. In newly published research of SGLT2 inhibitors for patients with heart failure and reduced ejection fraction (with or without -diabetes) findings of one agent have been presented and others are in late-stage cardiovascular outcomes trials. In one report, an SGLT2 inhibitor reduced cardiovascular death and hospitalization for heart failure.

FDA Fast Track designation was awarded to two SGLT2 inhibitors for patients with type II diabetes – onegent is approved to reduce the risk of cardiovascular death and the other agent can be used in patients with chronic heart failure to reduce the risk of hospitalization for heart failure. While SGLT2 inhibitors stand to be of great importance to the heart failure community as a whole, they may be especially innovative for adults with HFpEF who currently have no ideal therapeutic options targeted to their heart failure condition. An FDA decision is anticipated in 2020, but the work conducted to date has the potential of offering hope to many adults living with chronic heart failure with preserved ejection fraction.  

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