Why is telmisartan (an angiotensin receptor blocker) started after a drug-free interval following treatment with an Angiotensin Receptor-Neprilysin Inhibitor (ARNI)?

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Last updated: March 24, 2025 • View editorial policy

From the Guidelines

Telmisartan should be started 36 hours after discontinuing an ARNI (angiotensin receptor-neprilysin inhibitor) like sacubitril/valsartan to ensure patient safety, as recommended by the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1. This drug-free interval is necessary because ARNIs and ARBs (angiotensin receptor blockers) like telmisartan both affect the renin-angiotensin-aldosterone system, and immediate sequential use could lead to excessive blockade of this system. The washout period allows the ARNI components, particularly sacubitril, to be cleared from the body, preventing potential adverse effects such as hypotension, hyperkalemia, or renal dysfunction that could occur with overlapping therapy.

The rationale behind this recommendation is based on the potential harm of concomitant use of ACE inhibitors and ARNI, as demonstrated by the increased risk of angioedema and associated significant morbidity 2. The 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure also recommends that ARNI should not be administered concomitantly with ACE inhibitors or within 36 hours of the last dose of an ACE inhibitor 2.

When initiating telmisartan after this interval, it is recommended to start with a lower dose (such as 40 mg daily) and titrate as needed based on blood pressure response and tolerability. During the transition, it is crucial to monitor blood pressure, renal function, and potassium levels closely. The physiological basis for this recommendation is that sacubitril inhibits neprilysin, which degrades natriuretic peptides, while valsartan blocks angiotensin II receptors; allowing clearance of these effects before introducing another agent that affects the same system reduces the risk of adverse events.

Key points to consider:

  • ARNIs and ARBs should not be used concomitantly or within 36 hours of each other
  • The washout period allows the ARNI components to be cleared from the body, preventing potential adverse effects
  • Start telmisartan with a lower dose and titrate as needed based on blood pressure response and tolerability
  • Monitor blood pressure, renal function, and potassium levels closely during the transition
  • The recommendation is based on the potential harm of concomitant use of ACE inhibitors and ARNI, as demonstrated by the increased risk of angioedema and associated significant morbidity 1, 2.

From the Research

Rationale for Telmisartan Initiation After ARNI Treatment

  • The provided studies do not directly address why telmisartan is started after a drug-free interval following treatment with an Angiotensin Receptor-Neprilysin Inhibitor (ARNI) 3, 4, 5, 6, 7.
  • However, it can be inferred that the decision to initiate telmisartan after a drug-free interval may be related to the pharmacological properties of telmisartan and ARNI, as well as the potential for drug interactions or cumulative effects.
  • Telmisartan is an angiotensin II receptor antagonist that has been shown to be effective in reducing blood pressure and improving endothelial function in patients with essential hypertension 4, 5, 6, 7.
  • The studies suggest that telmisartan has a favorable tolerability profile and can be used as a first-line treatment option for the management of essential hypertension 4, 5.

Potential Considerations for Telmisartan Initiation

  • The long elimination half-life of telmisartan ensures that the drug provides effective reductions in blood pressure across the entire 24-hour dosage interval 5.
  • Telmisartan has been shown to have favorable effects on insulin resistance, lipid levels, left ventricular hypertrophy, and renal function, independent of its effect on blood pressure 5.
  • However, without direct evidence addressing the specific question of why telmisartan is started after a drug-free interval following ARNI treatment, it is difficult to provide a definitive answer.

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