Author + information
- Giuseppe Di Tano, MD∗ ( and )
- Luca Bettari, MD
- ↵∗Cardiology Department, Azienda Socio Sanitaria Territoriale, Cremona, Largo Priori 1, 26100 Cremona, Italy
We read with great interest the paper by Luo et al. (1) about early adoption of sacubitril/valsartan (angiotensin II receptor blocker neprilysin inhibitor [ARNI]) therapy for patients with heart failure and reduced ejection fraction (HFrEF) from the GWTG-HF (Get With the Guidelines–Heart Failure) registry.
The authors observed that only 2.3% of patients discharged alive from hospitals in the large GWTG-HF registry were prescribed ARNI therapy in the first 12 months following U.S. Food and Drug Agency approval and considered this evidence a confirmed barrier to successful implementation of evidence-based medicine in clinical practice.
We are not surprised by these results, principally because the study population included only patients discharged after acute HF hospitalization.
By definition, this population is an unstable cohort and does not meet the criteria that were established in PARADIGM-HF (Prospective Comparison of ARNI with ACEI [angiotensin-converting–enzyme inhibitor] to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial) (2), which analyzed only outpatients who were receiving optimal medical therapy and were in a stable chronic HF condition. Seventy percent of the study population was in New York Heart Association functional class II, and patients who were hospitalized within 3 months previously to screening accounted for only 19% of the cohort.
Hospitalized patients are a heterogeneous and intensively treated subset, thus patients who are initiated on sacubitril/valsartan therapy during hospitalization may be unable to tolerate continuation of the medication on discharge. Starting a patient during hospitalization for acute HF has never yet been studied. Therefore, the main obstacle to more widespread initiation of ARNI in HFrEF patients during acute HF hospitalization may be the lack of compelling evidence supporting that practice. A preliminary observation in a small sample study (3) reported that only 44% of patients who had received ARNI during their admission were discharged on this therapy. The most common reason for medication discontinuation was hypotension. Studies of outcomes for HFrEF patients started on ARNI during hospitalization are needed and are incoming.
Therefore, it would be interesting to know how many patients had started receiving the drug, the rate of patients who were unable to tolerate the medication at discharge, the most common reason for drug discontinuation, and the clinical differences between patients who continued the drug and those who discontinued it.
Today’s guidelines (4,5) recommend ARNI therapy only in chronic outpatients who remain symptomatic despite optimal treatment with an ACEI, a beta-blocker, and a mineralocorticoid-receptor antagonist. Therefore, the low rate of prescription observed by Luo et al. (1) may not translate tout-court (i.e., without elaboration) the real attitudes of the cardiologists to the implementation of this new therapy.
It is also our belief that there is a deleterious delay in the integration of new evidence into clinical practice; however, in this case the conclusion by the authors may not be completely adequate to confirm this assumption.
New data from large and structured surveys and registries of acute and chronic HF patients can provide additional elements to help us close the gap between evidence and real-world experience.
Please note: The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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