Heart Failure with Preserved Ejection Fraction and Therapeutic Approaches: A Systematic Review and Meta-analysis

Aims: Evidence is still lacking regarding optimal treatment for patients with heart failure with preserved ejection fraction (HfPEF). Our objective is to present an individual evaluation for each of the current available heart failure medications using a meta-analytical model.

Methods and Results: Using meta-analytical techniques we assessed the impact of standard systolic heart failure medications on the combined endpoint of all-cause mortality and/or hospitalization for heart failure as a primary endpoint and on mortality and heart failure hospitalization as separate secondary endpoints for patients with HfPEF. Studies were heterogeneous (Q test, p=0.01) and a random effect model was adopted for analysis. A total of 22 randomized and prospective observational studies of 16,802 patients were included; mean follow up duration was 27 months. Only angiotensin converting enzyme inhibitors (ACEIs) significantly reduced the composite end point of all-cause mortality and /or hospitalization for heart failure (HR 0.74 & 95% CI [0.61-0.89], p=0.01). As for all-cause mortality, only ACEIs (HR 0.57 & 95% CI [0.45-0.71], p=0.005), beta blockers (HR 0.63 & 95% CI [0.41-0.98], p=0.03) and statins (HR 0.41 & 95% CI [0.23-0.72], p=0.001) offered a survival benefit. As for hospitalization for heart failure, only digoxin had a significant effect (HR 0.77 & 95% CI [0.61-0.98], p=0.02).

Conclusions: Our analysis suggests that ACEI, beta blockers, statin and digoxin as potential medications that can improve outcomes in patients with HfPEF. However, prospective randomized studies are needed to better assess response to these medications.