MEDICATION DISCUSSION: HEART FAILURE

In Patients with Heart Failure, How Does the Use of Angiotensin Receptor Neprilysin Inhibitor (ARNI) Drugs Help Reduce Hospitalizations and Emergency Department Visits?

INTRODUCTION

Heart Failure (HF) is a very serious and fatal condition as the heart becomes unable to pump adequate blood supply for the body (Ho, KK., et al., 1993). In the United States of America (USA), there are nearly 6 million people who are afflicted by this illness. Due to this, statistics show that there are around 1 million hospitalizations or Emergency Department visits and roughly over 1 million hospital discharges in a year Roger, VL., et al., (2011). The Singapore Heart Foundation states that HF leads all other cases in mortality rates and morbidity rates in Singapore. Of Singapore's adult population (20-60 years old), there is an estimate that 1 to 2% are afflicted with HF, but for the older population (65 years and older), the percentage rises to around 6 to 10%.

The National University Heart Centre Singapore (NUHCS) lists current practices such as in an acute or emergency case of HF, the best-known practice is to supply vital amounts of oxygen with diuretic medications for shortness of breath, pain medications are also given when there is chest pain. However, those who suffer chronic cases of HF are advised to optimize control of hypertension and/or diabetes. Asides from this, chronic cases are given medications such as Enalapril an Angiotensin-Converting Enzyme Inhibitor (ACEI) that works by inhibiting enzymes that cause vasoconstriction. In turn, blood vessels dilate and in return increase blood supply to the heart. A new class of drug named Angiotensin Receptor Neprilysin Inhibitors (ARNI) have been recently approved to treat patients with chronic HF Nicolas, D., et al., 2020). This paper aims to provide information that ARNI can help reduce hospitalizations of patients with chronic HF.

DISCUSSION:

The use of Angiotensin-Converting Enzyme Inhibitor (ACEI) drugs have been widely used from the past in helping reduce mortality and morbidity of patients having chronic heart failure (HF). During the 1990s Enalapril, which is an ACEI drug, was added to the conventional therapy of HF and saw reduced hospitalizations to patients (Yusuf, S., et al., 1991). However, due to high mortality and morbidity rates to HF for many years, more work needed to be done to deal with the global problem of HF (Greenberg, B., 2020). One activity that plays a critical role in the progression and the development of HF is the neurohormonal activation of the body such as the Renin-Angiotensin-Aldosterone System (RAAS) and Sympathetic Nervous System (SNS) that causes blood vessels to constrict and water retention thereby elevating cardiac workload due to hypertension. That is why ACEI drugs were made to inhibit this activity, while another type of drug named Angiotensin Receptor Blocker (ARB) would immediately block the stimulus from its source to stop activation (Hartupee J., et al., 2017; and Cohn, JN., et al., 2000).

Other systems are also activated in the body to counteract and balance out the effects of RAAS and SNS. These are called Natriuretic Peptides (NPs) such as enkephalins, substance P, endothelin, and others that are vasoactive agents for the body. These agents, however, are metabolized by a neutral endopeptidase named Neprilysin. This peptide is found in many cell surfaces and is found in the circulation, therefore the vasoactive NPs are regulated and cannot produce their systemic effect (D'Elia, E., et al., 2017). Therefore Neprilysin Inhibitor (NI) drugs were made to stop the metabolism of the NPs by Neprilysin. On its own, however, NI was not found to be as effective as the ACEI drugs due to the fact that the RAAS has a more systemic effect than the NPs (Packer, M., et al 2002). So an alternative investigation by McMurray, JJ., et al., (2014) wherein they combined NI with ARB as there is better drug synergism between these two and named this new line as angiotensin receptor neprilysin inhibitors (ARNIs). In this new class of drugs, Sacubitril/valsartan is the first medication that is approved by the FDA for the treatment of patients with chronic heart failure (Türk UÖ., and Alioğlu E., 2019).

The next step was to compare sacubitril/valsartan to enalapril. McMurry, et al., discovered that sacubitril/valsartan showed a lower risk of elevation in serum potassium or serum creatinine and a lower risk of cough compared to enalapril. Another study by Velazquez, EJ., (2019), discovered that patients on sacubitril–valsartan therapy led to a greater reduction in the NT-proBNP concentration than enalapril therapy.

CONCLUSION

Clinical management of Heart Failure is very important especially that it is considered a pandemic and is affecting millions of people throughout the world. Therefore, through the development of a new line of drugs such as angiotensin receptor neprilysin inhibitors (ARNIs) wherein it has a greater effect on reducing mortalities and morbidities of patients with HF, future innovations can have an effective blueprint.

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