Beta-Blockers Reduce CV 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.

Reference

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