Proposal of a New Treatment Sequence Algorithm for Heart Failure with Reduced Ejection Fraction

Proposed Algorithm Step by Step

Step 1

In the first step, it is necessary to simultaneously begin the administration of a beta-blocker and a sodium-glucose cotransporter 2 inhibitor (SGLT2i). Beta-blockers are currently the most effective class of drugs for HFrEF, particularly in terms of prevention of sudden death. SGLT2i (gliflozins) have been shown to reduce the risk of hospitalization for heart failure and may also mitigate the short-term risk of worsening heart failure after starting beta-blocker therapy.

Step 2

The second step should be the addition of sacubitril/valsartan 1–2 weeks after the first step. If the patient has a systolic blood pressure < 100 mmHg, tolerance to valsartan in terms of hypotension should first be assessed. The hypotensive effect usually subsides with repeated doses or after adjusting the dose of concurrently administered diuretics.

Step 3

1–2 weeks after the second step, it is appropriate to add a mineralocorticoid receptor antagonist (MRA) if the patient has normal kalemia and does not have severely impaired renal function. The beneficial effect of neprilysin inhibitors and SGLT2i on renal function may improve tolerance to MRA. In patients with difficult-to-manage hypotension, MRA may also be the second step in treatment.

Who Should Use This Sequence?

According to the authors, this algorithm is one of many options and should be individualized based on existing conditions. It is more suitable for outpatient patients. Treatment with beta-blockers should be initiated in a hospital a few days after discontinuation of intravenous therapy in clinically euvolemic patients. With this algorithm, it is possible to achieve HFrEF therapy with the four basic drug groups in suitably selected patients within four weeks. Dose titration would follow thereafter.

Conclusion 

The proposed treatment sequence for heart failure with reduced ejection fraction, according to the authors, maximizes the likelihood of initiating highly effective therapy in a way that quickly leads to the prevention of hospitalizations and deaths while increasing the tolerability of concurrently and progressively administered treatment.

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Source: McMurray J. J. V., Packer M. How should we sequence the treatments for heart failure and a reduced ejection fraction? A redefinition of evidence-based medicine. Circulation 2021 Mar 2; 143 (9): 875−877, doi: 10.1161/CIRCULATIONAHA.120.052926.