Beta-Blockers Reduce CV Mortality in Heart Failure With Preserved Ejection Fraction

chest xray heart failure
chest xray heart failure
Most pharmacotherapies appear not to have significant effect on all-cause or cardiovascular mortality in heart failure with preserved ejection fraction.

Beta-blockers may lower all-cause and cardiovascular mortality in patients with heart failure with preserved ejection fraction (HFpEF), according to a meta-analysis published in Heart.

Researchers from the King’s College Hospital and the Imperial College Healthcare NHS Trust in London, United Kingdom, included data from 25 randomized controlled trials with a total of 18,101 patients with HFpEF with left ventricular (LV) ejection fraction ≥40%. Of the 25 trials, 6 involved beta-blockers, 5 involved angiotensin-converting enzyme (ACE) inhibitors, 6 involved angiotensin receptor blockers (ARB), and 5 involved mineralocorticoid receptor antagonists (MRAs).

The primary outcome was all-cause mortality with secondary outcomes being cardiovascular mortality, HF hospitalization, exercise capacity, quality of life, and biomarkers.

Beta-blocker therapy reduced all-cause mortality compared with placebo (relative risk [RR], 0.78; 95% CI, 0.65-0.94; P =.008) by 22%. In addition, cardiovascular mortality was reduced with beta-blockers compared with placebo (RR, 0.75; 95% CI, 0.60-0.94; P =.01) by 25%. However, none of the other individual agents significantly reduced all-cause or cardiovascular mortality. The same was true in a pooled analysis of drugs that specifically block the renin-angiotensin-adolesterone system (ACE inhibitors, ARBs, MRAs).

Although a meta-analysis of all the trials combined demonstrated that pharmacotherapy did not improve all-cause or cardiovascular mortality, it did reduce HF hospitalizations (RR, 0.88; 95% CI, 0.81-0.95; P =.002).

In terms of exercise capacity, there were no significant differences between treatment groups on exercise time, maximal oxygen consumption (VO2 max), and the 6-minute walking distance test. Quality of life scores improved with treatment (weighted mean difference, –1.63; 95% CI, –2.94 to –0.31; P =.001), and because heterogeneity was too high in the trials, the researchers could not compare biomarker outcomes.

The researchers pointed out that the trials involving beta-blockers used an LV ejection fraction threshold of 40%, whereas trials involving other drug classes (ACE inhibitors, ARBs, and MRAs) used higher thresholds.

“We did not further investigate causes of cardiovascular death, although pleiotropic effects of beta-blocker (such as its antiarrhythmic properties) are likely to be important,” the researchers wrote.

More trials in beta-blocker therapy involving this patient group are needed to confirm these findings.

Study Limitations

  • At the time of this meta-analysis, patients with LV ejection fractions ≥40% were defined as having HFpEF, but the category of HFmrEF (heart failure with mid-range ejection fraction; range, 40% to 49%) has since been introduced. None of the trials included reported on LV ejection fraction between 40% and 49%, and therefore the researchers could not assess the treatment effects in these mid-range patients.
  • The analyses were stratified by drug class. Other drugs such as vasodilators, calcium channel blockers, and digoxin do not exert their effects via the same mechanisms.

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Zheng SL, Chan FT, Nabeebaccus AA, et al. Drug treatment effects on outcomes in heart failure with preserved ejection fraction: a systematic review and meta-analysis [published online August 5, 2017]. Heart. doi:10.1136/heartjnl-2017-311652