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Do I need the drugs, doc? Heart failure drugs with preserved ejection fraction.

Evidence suggests heart failure patients with preserved ejection fraction could benefit from beta-blocker treatment, guidelines do not.

Jack O’Sullivan


There is a well-established list of medications that work in heart failure with a reduced ejection fraction. However, it is unclear if these drugs are clinically effective in patients with heart failure with a preserved ejection fraction (>40%).1 A recent systematic review and meta-analysis addressed this uncertainty.

What is heart failure with a preserved ejection fraction?

A patient with heart failure with a preserved ejection faction will have the typical signs and symptoms of heart failure (swollen ankles, orthopnoea, bibasilar lung crackles), but their left ventricular ejection fraction – the percentage of blood pumped out of the ventricles with each contraction – is adequate.1 Typically, an ejection fraction >40% is considered “preserved”.1

What did the authors do?

The study authors conducted a systematic review, extracting data from 25 published randomised controlled trials (RCTs) and then combined this data in a meta-analysis. The authors included RCTs that studied the effect of any drug on patients with heart failure with preserved ejection fraction and followed patients up with one or more of the following outcomes: all-cause mortality, cardiovascular mortality, heart failure hospitalisation, exercise capacity (6 min walk distance (6MWD), exercise duration, VO2 max), quality of life as measured using the Minnesota Living With Heart Failure Questionnaire (MLHFQ) and biomarkers (B-type natriuretic peptide (BNP), N-terminal pro-B-type natriuretic peptide (NT-proBNP)).

What did they find?

This systematic review included nine drug therapies for heart failure (Beta-blockers, ACE-inhibitors, Angiotensin-receptor blockers (ARBs), Minealocorticoid-receptor antagonists, digoxin, sildenafil, amlodipine, doxazosin, and sitaxsentan). They found that only beta-blockers significantly reduced all-cause and cardiovascular mortality; beta-blockers reduced all-cause and cardiovascular mortality by 22% and 25% respectively. Across the functional (e.g. 6MWD) and quality of life outcomes, only ARBs improved quality of life (measured with MLHFQ).

How does this fit in?

Neither the American College of Cardiology nor the European Society of Cardiology recommends the use of heart failure medications in heart failure patients with a preserved ejection fraction (>40%). This systematic review and meta-analysis suggest that these patients could benefit from beta-blocker treatment. These treatment decisions should naturally be considered in the context of an individual patient’s co-morbidities, wishes, and medication side effects

Jack O’Sullivan, Editorial Registrar BMJ EBM, Dr & DPhil Candidate at the University of Oxford

Conflict of interest: My DPhil (PhD) is funded by the Clarendon Fund, University of Oxford. I also receive income from Oxford University Hospitals for clinical work and hold grants from the National Institute for Health Research and the Primary Care Research Trust. I have no conflicts of interests.



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