New perspectives and future directions in the treatment of heart failure

Abstract

The management of heart failure has changed significantly over the last 30 years, leading to improvements in the quality of life and outcomes, at least for patients with a substantially reduced left ventricular ejection fraction (HFrEF). This has been made possible by the identification of various pathways leading to the development and progression of heart failure, which have been successfully targeted with effective therapies. Meanwhile, many other potential targets of treatment have been identified, and the list is constantly expanding. In this review, we summarise planned and ongoing trials exploring the potential benefit, or harm, of old and new pharmacological interventions that might offer further improvements in treatment for those with HFrEF and extend success to the treatment of patients with heart failure with preserved left ventricular ejection fraction (HFpEF) and other heart failure phenotypes.

Keywords: HFpEF; HFrEF; Heart failure; Treatment; Trials.

Fig. 1

The present and future of heart failure. Conventionally, the prevalence of heart failure is thought to be about 1.5% in the adult population. However, it might be substantially greater than that, as many cases remain undiagnosed, particularly amongst older people, and are usually only identified when symptoms are severe enough to require hospital admission. Several ongoing trials target different pathways that might contribute to disease progression. Success provides tentative insights into the likely mechanisms of progression, although off-target effects may lead to serendipitous effects (this is probably true of most effective treatments for heart failure). There may be many reasons for failure other than the lack of importance of the targeted mechanism. This may include a smaller than anticipated benefit with consequent lack of power, lack of target engagement, a mechanism that is important but only works in a specific subgroup (e.g., heart rate reduction in sinus rhythm) or one that is overwhelmed by competing risks (e.g., rivaroxaban 2.5 mg bd for advanced heart failure in sinus rhythm). Processing large volumes of routinely collected electronic health records using novel analytical approaches, such as artificial intelligence and machine learning, will provide new insights into disease classification, mechanisms of progression and therapeutic targets. Epidemiology, definition and management of heart failure are likely to be transformed in the next decade, with care and services matched to the individual patient’s needs in a “precision-medicine” approach