Drug therapy for patients with systolic heart failure after the PARADIGM-HF trial: in need of a new paradigm of LCZ696 implementation in clinical practice.

Gerasimos Filippatos,John Lekakis,Dimitrios Farmakis,John Parissis

doi:10.1186/s12916-015-0272-0

Gerasimos Filippatos, John Lekakis + Show 2 more

Open Access

https://doi.org/10.1186/s12916-015-0272-0

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Journal: BMC medicine	Publication Date: Feb 18, 2015
Citations: 30	License type: CC BY 4.0

Affiliation: University General Hospital Attikon

Abstract

Heart failure represents a primary cause of morbidity and mortality in older people and despite significant therapeutic advances, it is still characterized by important unmet needs, thus remaining a challenging field of clinical research. The recent PARADIGM-HF trial compared the novel compound LCZ696, a combination of the angiotensin receptor blocker valsartan and the neprilysin inhibitor sacubitril, versus the angiotensin-converting enzyme inhibitor enalapril in 8,442 patients with symptomatic chronic systolic heart failure. LCZ696 led to a 20% reduction in the rate of death or hospitalization for heart failure and a 16% reduction in the rate of all-cause death compared to enalapril at 3.5 years of follow-up. Despite those impressive results, the clinical application of this novel agent that requires the substitution of a cornerstone of current heart failure therapy, the angiotensin-converting enzyme inhibitors, should follow careful steps as imposed by the study design, the recruited population and the outcome in specific patient subgroups. Further insights into the effects of LCZ696 will be provided by the ongoing PARAGON-HF trial in patients with diastolic heart failure.

Highlights

Heart failure (HF) represents a main cause of morbidity and mortality and the first reason for hospital admission in older people [1]
Drug and device therapy has been proven beneficial for patients with systolic HF, currently termed HF with reduced ejection fraction (HFrEF), the same is not true for those with diastolic HF or HF with preserved ejection fraction (HFpEF), who roughly represent half of the total HF population and in whom no evidence-based therapy is yet defined [2]
At 3.5 years of follow-up, LCZ696 had led to a 20% reduction in the incidence rate of death or HF hospitalization and a 16% reduction in the incidence rate of all-cause death compared to enalapril, results that were highly statistically significant

Summary

Background

Heart failure (HF) represents a main cause of morbidity and mortality and the first reason for hospital admission in older people [1]. According to the trial’s subgroup analyses, LCZ696 was ‘less’ beneficial in ACEi-naïve patients, while LCZ696 led to a higher incidence of symptomatic hypotension compared to enalapril, which, did not result in a higher treatment discontinuation [5,6,8]. Those concerns are important in patients hospitalized for acute HF, in whom the use of oral medication including angiotensin aldosterone system inhibitors is not sufficiently guided by available evidence [9].

Conclusions

Findings

Patients on ARBs therapy