Abstract Aims The aim of our study was to investigate heterogeneity of health status treatment response of sacubitril/valsartan in patients with heart failure with reduced ejection fraction (HFrEF). Methods and results We leveraged data from CHAMP‐HF, an observational registry of 140 US clinics and 5026 outpatients with chronic HFrEF, where health status was serially assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ)‐12 Overall Summary Scale (range from 0 to 100; ≥20‐point improvement is a very large improvement). In 334 patients newly initiated on sacubitril/valsartan, we used hierarchical multivariable logistic regression (13 patient‐level characteristics as well as baseline KCCQ‐12 score) to calculate the odds ratio (OR) of any characteristic being associated with a very large health status improvement. A total of 104/334 (31.1%) of patients achieved the primary endpoint, where only worse baseline health status [KCCQ‐12 score of 0–60 points had an OR = 0.86/5‐point higher score (CI 0.79, 0.93)], and those with a KCCQ‐12 score of 60–80 points had an OR = 0.61/5‐point higher score (0.45–0.82), which was associated with a very large benefit. No other patient characteristic was associated with a very large health status improvement (P > 0.05). Conclusions We found that, after initiation of sacubitril/valsartan, only worse baseline health status was associated with very large health status improvement. Accordingly, a trial of therapy—particularly in those with worse symptoms, function, and quality of life—and assessing treatment response are likely to be the best prospective strategy.
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