Can a patient take Losartan (angiotensin II receptor antagonist) and Entresto (sacubitril/valsartan) together?

From the Guidelines

No, Vivan should not take losartan and Entresto together. These medications work through similar mechanisms affecting the renin-angiotensin-aldosterone system, and combining them can lead to dangerous side effects including severe hypotension (low blood pressure), hyperkalemia (high potassium levels), and kidney problems. Entresto already contains valsartan, which is an angiotensin receptor blocker (ARB) like losartan, so taking both medications would essentially double up on this class of drug. According to the guidelines outlined in the 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure 1, ARNI should not be administered concomitantly with ACE inhibitors or within 36 hours of the last dose of an ACE inhibitor. This is due to the potential signal of harm for concomitant use of ACE inhibitors and ARNI, including an increased risk of angioedema. Some key points to consider include:

• The benefits of ACE inhibitors and ARBs in decreasing heart failure progression, hospitalizations, and mortality rate have been consistently shown across the clinical spectrum of heart failure 1.
• The use of an ARNI is associated with hypotension and a low-frequency incidence of angioedema, and should be substituted for ACE inhibitors or ARBs in patients with symptomatic HFrEF 1.
• ARNI therapy should not be administered in patients with a history of angioedema because of the concern that it will increase the risk of a recurrence of angioedema 1. Patients should always consult their healthcare provider before making any medication changes, as they may need to transition from one medication to another under medical supervision. The healthcare provider will determine the appropriate medication regimen based on the patient's specific heart condition, kidney function, and overall health status.

From the FDA Drug Label

7.4 Dual Blockade of the Renin-Angiotensin System (RAS) Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy In most patients no benefit has been associated with using two RAS inhibitors concomitantly. In general, avoid combined use of RAS inhibitors.

Entresto contains sacubitril, a neprilysin inhibitor, and valsartan, an angiotensin II receptor blocker. Since losartan is also an angiotensin II receptor blocker, the combination of losartan and Entresto would be considered dual blockade of the RAS.

• The FDA recommends avoiding the combined use of RAS inhibitors due to increased risks of hypotension, syncope, hyperkalemia, and changes in renal function.
• Losartan and Entresto should not be taken together, as this combination may increase the risk of adverse effects. 2

From the Research

Combination Therapy with Losartan and Entresto

• The combination of losartan and Entresto (sacubitril/valsartan) in patients is not directly addressed in the provided studies, but we can infer some information from the available data.
• Losartan is an angiotensin II receptor blocker (ARB), and Entresto is a combination of sacubitril, a neprilysin inhibitor, and valsartan, an ARB 3.
• A study comparing sacubitril/valsartan with enalapril found that sacubitril/valsartan reduced the risk of hyperkalemia in patients with heart failure 4.
• Another study found that sacubitril/valsartan had better clinical, intermediate, and renal outcomes in heart failure compared to renin-angiotensin-aldosterone system inhibitors, including ARBs like losartan 3.
• However, the use of dual renin-angiotensin-aldosterone system inhibition, such as combining an ARB with an ACE inhibitor or another ARB, is generally not recommended due to the increased risk of hyperkalemia and acute kidney injury 5, 4.

Safety Considerations

• The safety of combining losartan and Entresto is a concern due to the potential for increased risk of hyperkalemia and other adverse effects.
• A study on polypharmacy highlights the importance of monitoring patients' active medication lists and deprescribing unnecessary medications to reduce the risks of adverse drug events 6.
• The combination of losartan and Entresto may increase the risk of hypotension, as seen in studies comparing sacubitril/valsartan with ACE inhibitors or ARBs 3.

Clinical Implications

• The decision to use losartan and Entresto together should be made on a case-by-case basis, taking into account the individual patient's medical history, current medications, and potential risks and benefits.
• Close monitoring of serum potassium levels, renal function, and blood pressure is essential when using this combination therapy 5, 4.
• Further studies are needed to fully understand the safety and efficacy of combining losartan and Entresto in patients with heart failure or other conditions.