A Promising Future for New Medications for Heart Failure: FDA Approvals Widen

Heart failure (HF) is a life-threatening condition that can also result in reduced functional capacity and a poor quality of life, requiring high medical costs to treat. HF affects over 64 million people worldwide and reducing these numbers has become a high priority for global health bodies. This is why significant investment has been made to develop new medications that can increase the effectiveness of heart failure treatment. 

In this article, we will discuss the optimism surrounding new medication for heart failure thanks to wider approval from the Food and Drug Administration (FDA).

Understanding Heart Failure: The first three pillars of heart failure treatment

Heart failure is also referred to as congestive heart failure and develops when the heart is unable to pump enough blood to the rest of the body. Commonly caused by the heart being able to fill up with a sufficient amount of blood or if the heart is too weak to pump the blood effectively.

Coronary artery disease is the most common cause of heart failure which is caused by a buildup of fatty deposits that clog the arteries, thus reducing blood flow and increasing the chances of a heart attack. However, there are a number of risks that could cause heart failure relating to age, lifestyle, and even ethnicity.

Here is a summary of the main factors that could increase the chances of heart disease:

• Age: Aging can result in a person’s heart weakening and becoming less able to pump blood effectively. This means people over the age of 65 have a higher risk of heart failure than younger adults. 
• Genetics: If your family has a history of heart failure then unfortunately, this also increases your chances of developing the condition as genes mutate over time. 
• An Unhealthy Lifestyle: Factors such as smoking, drinking alcohol regularly, an unhealthy diet, and illegal drug use can all increase the chances of heart failure. A lack of exercise and physical activity can also play a part, possibly leading to obesity which can cause a range of health problems, including HF. 
• Ethnicity: Black and African American people are more prone to heart failure than other races, sometimes occurring at an earlier age.
• Gender: Heart failure affects men and women but is more common among men who can develop it earlier in life. 
• Other Serious Conditions: If you already suffer from conditions relating to the heart, blood vessels, or other vital organs then the risk of HF is increased. Conditions can include HIV, SARs, COVID, lung disease, kidney disease, high blood pressure , diabetes, and more. 
• Cancer Treatments: Some cancer treatments such as chemotherapy and radiation can have a damaging effect on the heart.

The need for effective heart failure treatment has never been so pressing, with aging populations putting increased strain on health organizations. The symptoms of heart failure can often be improved by lifestyle changes, but in more severe cases, regular medication or devices such as pacemakers may be required.

Unfortunately, current heart failure medications have limitations and there are challenges that need to be overcome if they are to tackle HF effectively. Below are the three pillars of heart failure treatment, with details on how they work and the potential downsides.

ACE inhibitors, ARBs, and ARNIs

Angiotensin-converting enzyme (ACE) inhibitors, Angiotensin-2 receptor blockers (ARBs), and angiotensin receptor/neprilysin inhibitors (ARNIs) help to relax blood vessels and reduce blood pressure, allowing the heart to pump blood around the body more effectively.

A common side effect of ACE inhibitors is a dry and recurring cough, while a more serious issue is the medication causing a patient’s blood pressure to fall too low, sometimes resulting in kidney problems.

ARBs are sometimes preferred as they usually do not cause a cough, however, they can also cause low blood pressure, while also resulting in high levels of potassium in the blood.

Meanwhile, ARNIs can also cause kidney dysfunction, low blood pressure, and high levels of potassium. ARNI medication is a relatively new treatment and is a combination of an ARB and Neprilysin Inhibitor, relaxing blood vessels and removing excess bodily fluid.

Entresto® (sacubitril/valsartan) is the most-prescribed ARNI and studies show it to be superior in terms of safety and effectiveness when compared to ACE and ARB alternatives.

Beta Blockers

Beta-blockers slow down the heart, protecting it from the effects of adrenaline and noradrenaline, the “fight or flight” chemicals in the body that put additional strain on the heart. In the US, Metoprolol succinate (Toprol XL) and carvedilol (Coreg) are the two most commonly prescribed beta blockers for heart failure.

Beta-blocker side effects may include blurred vision, tiredness, dizziness, memory problems, and depression.

Mineralocorticoid Receptor Antagonists (MRAs)

Mineralocorticoid antagonists (MRAs) are weak diuretics that can reduce the chances of death and long-term issues related to HF. They work by making patients pass more urine, lowering blood pressure, and reducing fluid around the heart.

Possible side effects of MRAs include sleeping difficulties, dizziness, and headaches, while a more serious side effect is the potential to increase potassium in the blood to dangerously high levels.

Exploring New Frontiers in New Heart Failure Medications

The good news is that there are a number of ongoing clinical trials that are exploring the benefits of new heart failure treatments. This includes the analysis of new drugs, considering new mechanisms and pathways, gene therapies, and personalized medicine.

Studies and clinical trials follow a few key approaches and strategies to help tackle the effects of heart failure, including:

• There are a number of new pathways and mechanisms that are being investigated to progress heart failure treatments. These include cardiac remodeling, neurohormonal activation, myocardial Ischemia, endothelial dysfunction, inflammation, and more.
• Gene therapies and stem cell-based treatments that aim to modify the patient’s genes have also become a key consideration to combat heart failure. From using viral vectors to deliver therapeutic genes to the heart cells, to gene-editing techniques such as CRISPR-Cas9.
• Precision medicine (personalized medicine) can be very effective when it comes to managing heart failure and conducting a thorough analysis of the patient with a range of techniques. Analysis techniques may include pharmacogenomics, biomarkers, artificial intelligence, and remote monitoring.

Advances in Heart Failure: What’s in the Pipeline?

Two new drugs have been approved by the FDA in recent years. Ivabradine (Corlanor) and the ARNI, sacubitril/valsartan (Entresto). Studies show that Entresto in particular has helped to reduce hospital visits and deaths related to heart failure.

Meanwhile, there are other drugs in the pipeline, including Omecamtiv Mecarbil which helps the heart pump more blood and can potentially reduce the chances of death. The FDA is also prioritizing the review of Vericiguat, a soluble guanylate cyclase (sGC) inhibitor that has also shown great promise in terms of reducing HF-related deaths and hospital visits.

Further studies are also being conducted on Sodium-glucose cotransporter-2 (SGLT2) inhibitors, initially, a drug prescribed to treat diabetes, it could also provide effective treatment for HF patients.

Challenges and Opportunities

Developing new medication for conditions such as heart failure is a complex and challenging process. For example, if a patient is taking multiple forms of medication then a new treatment could result in adverse drug interactions, jeopardizing a person’s safety. Furthermore, strict regulatory requirements also create barriers when it comes to new drugs being granted approval. In addition to safety concerns and regulations, the multifactorial nature of heart disease presents significant obstacles.

The overall goal of heart failure treatment is to improve a person’s quality of life, this can be achieved with better management of symptoms, targeting the cause of heart failure to reduce the feeling of fatigue, coughs, swelling, and any other symptoms. This can help to slow the condition’s progression, preserve the functionality of the heart, and reduce the number of times a person needs to visit the hospital. Most importantly, new and more effective medication can increase the chances of survival for anyone experiencing HF.

The Road to Zero Heart Failure

To achieve the goal of zero heart failure, continued research is required, combined with better collaboration among scientists, clinicians, and pharmaceutical companies. The effectiveness of research can also be further optimized with the help of new technologies such as AI and machine learning.

AI and ML algorithms can speed up the analysis of vast amounts of biomedical data from a wide range of sources, identifying trends, patterns, and correlations that may be missed by manual human analysis. Machine learning models can also effectively predict new drug targets by checking data related to known drug interactions, improving the safety of new treatments. The possibilities of AI and ML from a medical perspective are practically limitless, significantly improving processes such as biomarker discovery, target validation, drug toxicity predictions, and more.

This utilization of emerging technologies gives fresh hope to heart failure studies and clinical trials, resulting in faster turnarounds, better accuracy, and safer treatments.

Conclusion

Heart failure is a global problem, affecting over 64 million people across the world and although there are a number of existing treatments, they come with several side effects that could potentially result in other serious conditions. With continued research, ongoing studies, and the use of technology such as AI and machine learning, there is increased optimism that new treatments can be developed that are symptomless, drastically increase survival rates, and accelerate medical science.

New medications such as Corlanor and Entresto, as well as drugs currently being researched like Omecamtiv Mecarbil and SGLT2 provide a lot of hope for the future of heart failure patients. With better symptom management, the quality of life for HF sufferers can be greatly improved, the first step on the road to zero heart failure.

FAQS

What is the most effective drug for heart failure?

There is no one drug that can be considered the most effective treatment for heart failure as it is entirely dependent on the individual and the level of the condition. However, Entresto is a newly approved drug that has been shown to have a high success rate in terms of reducing hospital visits and the number of deaths among HF sufferers.

What are the big four heart failure drugs?

The big four heart failure drugs are:

• Angiotensin-Converting Enzyme (ACE) Inhibitors, Angiotensin Receptor Blockers (ARBs), or Angiotensin Receptor-Neprilysin Inhibitors (ARNIs)
• Mineralocorticoid Receptor Antagonists (MRAs)
• Sodium‐glucose cotransporter 2 inhibitors (SGLT2i)
• Beta-Blockers

What is the new wonder drug for heart failure?

There is no ‘wonder drug’ for heart failure, however, sacubitril/valsartan which is marketed under the brand name Entresto has shown significant promise and could be a life-changing treatment for many people.