Heterogeneity of health status treatment response with sacubitril/valsartan: insights from the CHAMP-HF registry.

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.