Influence of LCZ696 on 30-Day Heart Failure Readmission

Study Questions:

When compared with enalapril, does treatment with LCZ696 reduce rates of 30-day readmissions following hospitalization for heart failure (HF)?

Methods:

PARADIGM-HF was a multicenter, prospective, double-blind randomized clinical trial comparing the risk of death and of hospitalization for HF in patients taking LCZ696 200 mg twice daily versus enalapril 10 mg twice daily. Eligibility criteria included New York Heart Association class II-IV symptoms and an ejection fraction of ≤40%. Prior to randomization, all subjects underwent a sequential run-in phase to ensure tolerability of both study medications at target doses. After successful completion of the run-in phase, a total of 8,399 patients were randomized in 1:1 fashion to double-blind treatment with either LCZ6967 or enalapril. The study had a median follow-up of 27 months. The primary endpoint of PARADIGM-HF was a composite of death from cardiovascular causes or a first hospitalization for HF. The investigators now present a post-hoc analysis that compares 30-day all-cause readmissions between the two study drugs after the index HF hospitalization.

Results:

Mean age was 64 years in both study groups. Ischemic cardiomyopathy was equally present in 60% of patients. When compared with enalapril, treatment with LCZ696 successfully lowered rates of hospital readmission within 30 days after an index HF hospitalization. These findings were statistically significant for all-cause (p = 0.031) and HF-related readmissions (p = 0.006). Moreover, this benefit of freedom from rehospitalization extended over to 60 days in the LCZ696 group when compared to the enalapril group (all-cause readmissions: p = 0.045, HF readmissions: p = 0.01).

Conclusions:

Following an index HF hospitalization, all-cause 30-day readmission rates were lower with LCZ696 when compared to enalapril.

Perspective:

The article dissects the important aspect of HF hospitalizations and 30-day readmissions in the PARADIGM-HF study cohort. The authors make a compelling argument in favor of LCZ696. This is based on a post-hoc analysis of the PARADIGM-HF cohort that showed LCZ696 lowered all-cause and HF-associated 30-day readmissions when compared to enalapril. This outcome was further validated in the 60-day post-index HF hospitalization period, indicating longer freedom from rehospitalization.

Note that the 30-day all-cause and HF-associated readmissions were not a prespecified endpoint of the PARADIGM-HF study. The investigators point out that in subgroup analyses, patients ages >65 years and patients enrolled in the United States had a trend toward lowered all-cause 30-day readmissions. However, both groups did not reach statistical significance. In another subgroup analysis, which was based on geographic distribution, the largest population enrolled was from Central Europe. This group had the least benefit in lowering all-cause and HF-related readmissions. In contrast, the Western Europe cohort (second largest group enrolled) achieved the most benefit, particularly in lowering 30-day HF-associated readmissions. These geographic variations may need to be addressed in future investigations.

Overall, the authors make a compelling argument in favor of LCZ696 reducing all-cause and HF-associated 30-day readmissions. Of particular note, this study is the first double-blind, randomized clinical trial demonstrating a pharmacologic intervention that lowers 30-day readmissions post-HF hospitalization. In this regard, LCZ696 has the potential to lower costs associated with 30-day readmissions, which may compensate for the higher cost of this new medication.

Acknowledgement: The author thanks Dr. Asad Ghafoor for assisting with writing this Journal Scan.

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure

Keywords: Cardiomyopathies, Enalapril, Heart Failure, Hospitalization, Ischemia, Patient Readmission, Primary Prevention, Stroke Volume


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