Pharmacotherapy sequencing strategies for patients with heart failure with reduced ejection fraction: a cost–utility analysis

Background

Standard pharmacotherapy for patients with heart failure with reduced ejection fraction (HFrEF) comprises "quadruple therapy" with a renin–angiotensin system inhibitor, a β-blocker, a mineralocorticoid receptor antagonist, and a sodium–glucose cotransporter-2 inhibitor. Randomized controlled trials evaluating different sequencing strategies for initiating and titrating these medications are lacking. We sought to compare costs for various HFrEF quadruple therapy sequencing strategies.

Methods

We used an individual-based state-transition microsimulation model to compare cost utility for 12 sequencing strategies with either weekly or biweekly medication adjustments for treatment-naive patients with HFrEF. We conducted a probabilistic analysis with a lifetime horizon from the public-payer perspective, along with a deterministic sensitivity analysis and 2 scenario analyses. We estimated costs, quality-adjusted life years (QALYs), incremental net monetary benefit (NMB) at a willingness-to-pay threshold of $50 000/QALY, and incremental cost-effectiveness ratios (ICERs) of each strategy versus the conventional approach.

Results

Over a lifetime, the 12 strategies resulted in costs ranging from $76 440 to $79 338, QALYs ranging from 9.55 to 9.72, and incremental NMB ranging from $2233 to $6529. Compared with the conventional sequencing strategy of starting and titrating biweekly 1 medication at a time, other strategies had ICERs ranging from $11 175 to $22 492. The simultaneous initiation of all 4 medications with subsequent biweekly adjustment had the highest probability of being the most cost-effective strategy at the specified willingness-to-pay threshold.

Interpretation

Simultaneous initiation of the 4 standard HFrEF medications with biweekly adjustment provided the highest cost utility compared with other strategies. Systems of care are needed to enable rapid initiation and sustained use of HFrEF medications.