Surreal illustration of a heart intertwined with technology and nature, symbolizing heart failure treatment.

Heart Failure Treatment: Navigating the Latest Advances and Unanswered Questions

Samir D’Costa in Health & Wellness July 2025 • 4 min read.

"A comprehensive look at the evolving landscape of heart failure therapy, from evidence-based treatments to emerging innovations and persistent challenges."

In June 2017, the medical community marked the 30th anniversary of a landmark publication that revolutionized heart failure (HF) treatment. The Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS) demonstrated for the first time that pharmacological interventions could significantly improve outcomes for patients with this debilitating condition.

Over the subsequent three decades, a multitude of randomized controlled trials have built upon this foundation, leading to gradual improvements in patient care and overall outcomes for individuals living with heart failure.

Despite these significant strides, heart failure remains a major public health challenge. Affecting over 10% of people over the age of 70, heart failure is a chronic, progressive syndrome that places a substantial burden on healthcare systems, especially in the face of an aging population.

Evidence-Based Therapies: What Works in Heart Failure Treatment?

Surreal illustration of a heart intertwined with technology and nature, symbolizing heart failure treatment.

Contemporary treatment strategies for heart failure with reduced ejection fraction (HFrEF) typically involve a triple-therapy approach. This includes an angiotensin-converting enzyme inhibitor (ACEI) or, if not tolerated, an angiotensin II type I receptor blocker (ARB), a beta-blocker (BB), and a mineralocorticoid/aldosterone receptor antagonist (MRA). This potent combination targets multiple neurohormonal pathways, demonstrating its ability to reduce mortality and improve survival in numerous landmark trials.

ACE inhibitors (ACEIs) are a cornerstone in HF treatment. Clinical trials have consistently demonstrated their ability to reduce mortality and morbidity, as well as improve quality of life. The CONSENSUS trial in 1987 and the Studies of Left Ventricular Dysfunction (SOLVD) trial in 1991 showed significant reductions in the risk of mortality with enalapril compared to placebo.

Angiotensin Receptor Blockers (ARBs): ARBs are an alternative for patients who cannot tolerate ACEIs.
Beta-Blockers (BBs): Beta-blockers are a cornerstone in the pharmacological therapy of HFrEF, having shown in multiple randomized trials to reduce long-term mortality and morbidity.
Mineralocorticoid Receptor Antagonists (MRAs): MRAs are strongly recommended in all patients with HFrEF and systolic left ventricular function below 35% who remain symptomatic after optimal medical treatment with ACEIs and a BB.

The emergence of angiotensin receptor neprilysin inhibitors (ARNIs) represents a significant advancement in heart failure therapy. By simultaneously inhibiting neprilysin and blocking the angiotensin II receptor, ARNIs offer a dual mechanism of action that enhances natriuresis, promotes vasodilation, and suppresses inflammation. The PARADIGM-HF trial demonstrated the superiority of sacubitril/valsartan (an ARNI) over enalapril in reducing the risk of cardiovascular death and heart failure hospitalization.

The Future of Heart Failure Therapy: Personalized Approaches and Ongoing Research

Despite the significant progress made in heart failure therapy over the past few decades, numerous unanswered questions remain. Tailoring treatment strategies to individual patient characteristics and addressing the underlying causes of heart failure are critical areas of focus. Ongoing research efforts are exploring novel therapeutic targets, refining existing treatment approaches, and developing personalized strategies to improve outcomes for all patients with heart failure. Several trials are currently underway to evaluate ARNI, SGLT2 inhibitors, and Cardiac-specific myosin activators.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1093/icvts/ivy282, Alternate LINK

Title: What’S New In Heart Failure Therapy 2018?†

Subject: Cardiology and Cardiovascular Medicine

Journal: Interactive CardioVascular and Thoracic Surgery

Publisher: Oxford University Press (OUP)

Authors: Julian G Westphal, Tarek Bekfani, Paul Christian Schulze

Published: 2018-10-09

Everything You Need To Know

What is the triple therapy approach for treating heart failure, and why is it so important?

The triple therapy approach for heart failure with reduced ejection fraction (HFrEF) typically includes an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II type I receptor blocker (ARB) if an ACEI isn't tolerated, a beta-blocker (BB), and a mineralocorticoid/aldosterone receptor antagonist (MRA). This combination is important because it targets multiple neurohormonal pathways. The implications of this therapy are significant as it has demonstrated the ability to reduce mortality and improve survival in numerous landmark trials for individuals living with heart failure.

Why are angiotensin-converting enzyme inhibitors (ACEIs) a cornerstone in treating heart failure, and what impact do they have?

Angiotensin-converting enzyme inhibitors (ACEIs) are essential in treating heart failure because they've consistently shown in clinical trials to reduce mortality and morbidity, while also improving the quality of life for patients. Landmark trials like the CONSENSUS trial in 1987 and the SOLVD trial in 1991 highlighted how enalapril significantly reduced the risk of mortality compared to a placebo. ACEIs work by blocking the conversion of angiotensin I to angiotensin II, leading to vasodilation and reduced blood pressure, which eases the workload on the heart. The implications of using ACEIs include improved heart function and overall well-being for heart failure patients.

What are angiotensin receptor neprilysin inhibitors (ARNIs), and how do they improve heart failure therapy?

Angiotensin receptor neprilysin inhibitors (ARNIs) represent a notable advancement in heart failure therapy. They function by simultaneously inhibiting neprilysin and blocking the angiotensin II receptor. This dual mechanism enhances natriuresis (sodium excretion), promotes vasodilation, and suppresses inflammation. The PARADIGM-HF trial demonstrated that sacubitril/valsartan, an ARNI, was superior to enalapril in reducing the risk of cardiovascular death and heart failure hospitalization. The implications of ARNIs are significant, offering a more effective treatment option for reducing heart failure-related events and improving patient outcomes.

What is the role of beta-blockers (BBs) in treating heart failure with reduced ejection fraction (HFrEF)?

Beta-blockers (BBs) are a cornerstone in the pharmacological therapy of HFrEF because multiple randomized trials have shown that they reduce long-term mortality and morbidity. By blocking the effects of adrenaline, beta-blockers reduce heart rate and blood pressure, decreasing the heart's workload. This leads to improved heart function and reduced symptoms of heart failure. The implications of using beta-blockers include a better prognosis and enhanced quality of life for individuals with heart failure.

When are mineralocorticoid receptor antagonists (MRAs) recommended for treating heart failure, and what benefits do they offer?

Mineralocorticoid receptor antagonists (MRAs) are strongly recommended for patients with HFrEF and systolic left ventricular function below 35% who remain symptomatic after optimal medical treatment with ACEIs and a BB. MRAs, such as spironolactone and eplerenone, block the effects of aldosterone, a hormone that can cause sodium and water retention, leading to increased blood volume and pressure. By blocking aldosterone, MRAs help reduce fluid overload, improve heart function, and decrease the risk of hospitalization. The implications of using MRAs include improved symptom control and better outcomes for heart failure patients who have persistent symptoms despite other treatments.