What is an ARNI?

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The available treatments for high blood pressure form a long-standard arsenal, complete with frequently updated guidelines by an expert panel. Yet, half of the 75 million Americans diagnosed with hypertension have uncontrolled blood pressure levels. The resulting strokes and organ damage place a large physical, emotional, and financial burden on patients, families, and the health care system. Obviously, new and better treatment strategies are needed.

Research suggests that an approved heart failure treatment—a drug combination called an ARNI—could be an answer to better hypertension control. ARNIs combine angiotensin receptor blockers (ARBs), such as drugs like valsartan that have been used for decades in cardiovascular care, with a newer drug type called a neprilysin inhibitor (NI). NIs, a type of vasoactive drug, have been explored since the early 2000s. NIs cause blood vessels to relax and dilate by blocking actions of the protein neprilysin. Alone, NIs are not better than existing cardiac treatments.

Together with angiotensin-acting drugs, though, NIs reduce the risk of death and hospitalization even more than existing treatments alone. Early combinations of NIs with classic heart drugs called angiotensin-converting enzyme inhibitors (ACE-Is) caused more side effects together than with either drug alone. One serious problem, called angioedema, developed often, and especially in people with high blood pressure. Angioedema causes swelling that is like hives but deeper into the skin; it can be life threatening if the throat, airway, and face swell. Now, NI drugs are only combined with ARBs in approved and researched forms.

Heart failure approval first

The first ARNI approved in the US, sacubitril/valsartan (Entresto), is considered a breakthrough treatment for heart failure. It was studied in more than 8,000 patients—one of the largest heart failure trials ever—before its approval. Use of Entresto to treat heart failure in patients with ejection fractions <40% (low pumping strength) was highly recommended in 2016 by the American College of Cardiology and American Heart Association.

Entresto was approved by the US FDA for heart failure in 2015 but has not yet been approved to treat hypertension in Americans. Because one of the biggest side effects in trials and early use was low blood pressure, research is focusing on its possible use as an antihypertensive treatment, too. Similar products are being developed and studied for heart failure and hypertension and are being studied for other conditions, like dementia, as well.

Using an ARNI safely

ARNI tablets are taken by mouth, like other drugs for heart failure and hypertension. The starting dose for people new to heart medication, or people who have only used low doses of ACE-Is or ARBs before, is 24 mg of sacubitril/26 mg of valsartan twice daily. For people who switch to the ARNI from an ACE-I or ARB, 49 mg/51 mg is a better starting dose. Anyone taking an ACE-I has to stop that drug and wait 36 hours before starting an ARNI.

Either starting dose should be doubled as tolerated every two to four weeks. The target dose of sacubitril/valsartan for all people is 97 mg/103 mg twice daily. The most common side effects—such as dizziness, cough, and low blood pressure—are similar to those of other hypertension treatments.

Research about ARNIs in hypertension is still new, so Entresto is not yet in hypertension treatment guidelines, but heart failure guidance has been updated to include this new option. Professionals are still trying to determine which patients are most likely to safely benefit from ARNIs, too. You might want to discuss the new ARNI medicine with your heart doctor if you have been diagnosed with heart failure and have a history of high blood pressure.

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