Wprowadzenie sakubitrylu + walsartanu w leczeniu niewydolności serca. Którzy pacjenci mogą odnieść największe korzyści z tego nowego leku? Artykuł przeglądowy

Abstrakt

Heart failure (HF) is a significant cause of morbidity and mortality in developed countries. Chronic activation of RAAS has been implicated in remodeling of the heart and progression of HF. In the past pharmacological therapies have been aimed at suppression of RAAS with β-blockers, ACE inhibitors, and mineralocorticoid receptor blockers being the cornerstone of HF therapy. Over the recent decades as the protective role of natriuretic peptides (ANP and BNP) became more clear in HF, efforts have been made in manipulating these vasoactive peptides to counter remodeling of the heart in HF patients. Initial strategies involved use of recombinant natriuretic peptides, however trials failed to show therapeutic benefits in HF patients. The next strategy was inhibition of neprilysin, an enzyme that degrades natriuretic peptides, with the goal of increasing endogenous levels of ANP and BNP. Over the years multiple trials failed to demonstrate superiority of various combination of drugs targeting neprilysin inhibition over the standard therapy (ACE inhibitor or ARB). A breakthrough was finally made when PARADIGM-HF trial showed that combination therapy with angiotensin receptor-neprilysin inhibitor (ARN-I) significantly lowered cardiovascular mortality and hospitalization as well as all-cause mortality in HFrEF (heart failure with reduced ejection fraction) patients compared to treatment with a proven dose of ACE inhibitor (enalapril 10 mg). Although ARN-I is FDA (US Food and Drug Administration) approved, currently its use remains limited in many countries because of lack of clinical experience and its potential life-threatening adverse effects (e.g. angioedema). It is recommended as a second-line agent in place of ACE inhibitor in HErEF patients who remain symptomatic despite optimal treatment with HF drugs. Despite the valuable lessons learned from PARADIGM-HF trial many questions are still left unanswered in regard to efficacy and safety of ARN-I in other subset of patients with HF who may benefit from its use.