Clinical and Economic Implications of Cardiac Resynchronization Timing and Longitudinal Medication Titration: A Real-world Medicare Analysis

BACKGROUND: Despite advances in guideline-directed medical therapy (GDMT) for heart failure (HF) with reduced ejection fraction, challenges with uptitration may delay optimal treatment. Cardiac resynchronization therapy (CRT) improves clinical outcomes, yet optimal sequencing of CRT and GDMT remains uncertain. We sought to characterize longitudinal GDMT titration and evaluate associations between CRT timing and outcomes among US patients. METHODS: A retrospective cohort study of 6334 Medicare beneficiaries with an identifiable incident HF diagnosis who will receive CRT between 2018 and 2022. Early CRT was defined as implantation within 1 year of diagnosis. Medication use was assessed by medication possession ratios of ≥0.8 in quarterly intervals. Outcomes were compared using propensity score overlap-weighted models. RESULTS: GDMT uptake increased sharply after the incident HF diagnosis but plateaued quickly with consistent medication use remaining low. Early CRT (n = 3777) was associated with lower adjusted risk of composite all-cause death or HF exacerbation (hazard ratio 0.80, 95% confidence interval [CI] 0.72-0.89), all-cause death alone (hazard ratio 0.79, 95% CI 0.69-0.90), and fewer HF exacerbations (incident rate ratio 0.66, 95% CI 0.58-0.75) vs late CRT (n = 2557). Early CRT was also associated with lower inpatient and emergency department use, Medicare expenditures, and HF-related out-of-pocket costs after CRT implant. CONCLUSIONS: Early CRT was associated with lower mortality, fewer HF exacerbations, and lower health care use, supporting reconsideration of GDMT and CRT treatment sequencing.