Contemporary Drug Treatment of Advanced Heart Failure with Reduced Ejection Fraction

Abstract

The introduction of multiple new pharmacological agents over the past three decades in the field of heart failure with reduced ejection fraction (HFrEF) has led to reduced rates of mortality and hospitalizations, and consequently the prevalence of HFrEF has increased, and up to 10% of patients progress to more advanced stages, characterized by high rates of mortality, hospitalizations, and poor quality of life. Advanced HFrEF patients often show persistent or progressive signs of severe HF symptoms corresponding to New York Heart Association class III or IV despite being on optimal medical, surgical, and device therapies. However, a subpopulation of patients with advanced HF, those with the most advanced stages of disease, were often insufficiently represented in the major trials demonstrating efficacy and tolerability of the drugs used in HFrEF due to exclusion criteria such as low BP and kidney dysfunction. Consequently, the results of many landmark trials cannot necessarily be transferred to patients with the most advanced stages of HFrEF. Thus, the efficacy and tolerability of guidelinedirected medical therapies in patients with the most advanced stages of HFrEF often remain unsettled, and this knowledge is of crucial importance in the planning and timing of consideration for referral for advanced therapies. This review discusses the evidence regarding the use of contemporary drugs in the advanced HFrEF population, covering components such as guideline HFrEF drugs, diuretics, inotropes, and the use of HFrEF drugs in LVAD recipients, and provides suggestions on how to manage guideline-directed therapy in this patient group.

Heart failure: an update from the last years and a look at the near future

“…321 The efficacy and tolerability of GDMT in patients with the most advanced stages of HFrEF often remain unsettled. 150,322,323…”

“…The HFA‐ESC advanced HF definition was associated with a higher risk of all‐cause mortality or first HF hospitalization (adjusted HR 1.98; 95% CI 1.57–2.50; P < 0.001) 321 . The efficacy and tolerability of GDMT in patients with the most advanced stages of HFrEF often remain unsettled 150,322,323 …”

Updates in heart failure: sodium glucose co-transporter 2 inhibitors and beyond – major changes are coming

“…67 Medical management of patients with advanced HF remains a largely unmet clinical need. 55,[68][69][70] Current guidelines report that long-term mechanical circulatory support (MCS) and heart transplantation have to be considered also in patients with NYHA class II at high risk for HF progression. These patients need to be referred to or discussed with advanced HF centres as well as those with NYHA class III or IV (Fig.…”

Promising directions in the treatment of chronic heart failure: improving old or developing new ones?

“…Так называемые акваретики (ваптаны) с успехом применяются у пациентов с ХСН, ассоциированной с выраженной гиперволемической гипонатриемией [1]. Так как терапия наиболее изученным селективным конкурентным антагонистом почечных V2-рецепторов вазопрессина толваптаном не оказывает влияния на прогноз пациента с ХСН, основное внимание в настоящее время уделяется применению двойных антагонистов вазопрессина, имеющих потенциальное преимущество за счет одновременной блокады васкулярных V1a рецепторов [55,56]. В частности, в настоящее время выполняется несколько экспериментальных и клинических исследований, сфокусированных на анализе эффективности и безопасности неселективного антагониста V1a/V2-рецепторов вазопрессина пекаваптана [57,58].…”