Midodrine in the management of heart failure with reduced ejection fraction: a systematic review

Abstract Background Guideline‐directed medical therapy (GDMT) has significantly improved outcomes of patients with heart failure with reduced ejection fraction (HFrEF). However, the presence of hypotension often limits GDMT up‐titration. Midodrine is a peripheral vasoconstrictor that may improve blood pressure in select patients with HFrEF and enable the optimisation of medical therapy. Aims This systematic review aimed to evaluate the safety and efficacy of midodrine in the treatment of HFrEF. Method A systematic review was registered (CRD42024594291) and conducted in accordance with PRISMA guidelines. A search was completed on 29 September 2024 among PubMed, Medline, EMBASE, Cochrane and SCOPUS databases. Primary outcome measures included tolerance of GDMT, left ventricular ejection fraction (LVEF) recovery, heart failure hospitalisations and all‐cause mortality. Results Five studies were included (12 063 HFrEF patients). A meta‐analysis was precluded due to heterogeneity in study design, population and reported outcomes. Two studies suggested that midodrine was associated with an increase in the prevalence of patients prescribed GDMT and improvements in LVEF. Two studies concluded that midodrine use was associated with increased hospitalisations, intensive care visits and mortality. One study suggested midodrine use was safe in patients with cancer and heart failure. Conclusion There is a lack of high‐quality evidence to support the use of midodrine to facilitate GDMT up‐titration in HFrEF. Supporting evidence of improving GDMT tolerance and LVEF stems from observational studies without comparator groups. Randomised trials are urgently needed to determine whether midodrine safely facilitates GDMT in HFrEF patients.