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Evidence summaries

Drugs for Chronic Heart Failure with Preserved Ejection Fraction

Beta-blockers may improve cardiovascular mortality and mineralocorticoid receptor antagonists (MRA) and angiotensin receptor neprilysin inhibitors (ARNI) appear to reduce heart failure hospitalisation in heart failure patients with preserverd ejection fraction. Level of evidence: "C"

The quality of evidence is downgraded by study limitations (unclear allocation concealment and blinding), and by imprecise results.

Summary

A Cochrane review [Abstract] 1 included 41 studies with a total of 23 492 subjects with chronic heart failure with preserved ejection fraction. Ten studies (n=3 087) investigated beta-blockers, 13 (n=4 459) mineralocorticoid receptor antagonists (MRA; 10 spironolactone, 2 eplerenone, and 1 canrenone), 8 (n=2 061) angiotensin converting enzyme inhibitors (ACEI), 8 (n=8 755) angiotensin receptor blockers (ARB), and 3 studies (n=7 702) investigated angiotensin receptor neprilysin inhibitors (ARNI).

Beta-blockers reduced cardiovascular mortality compared to control (RR 0.78, 95% CI 0.62 to 0.99; NNTB 25; 3 studies, n=1 046). However, no effect was observed when the analysis was limited to the only study with a low risk of bias (RR 0.81, 95% CI 0.50 to 1.29; 1 study n=643). There was little to no effect on all-cause mortality (RR 0.82, 95% CI 0.67 to 1.00; 4 studies, n=1 105). The effects on heart failure hospitalisation, hyperkalaemia, and quality of life were uncertain.MRA treatment reduced heart failure hospitalisation compared to control (RR 0.82, 95% CI 0.69 to 0.98; NNTB 41; 3 studies, n=3 714), but little or no effect on all-cause (RR 0.91, 95% CI 0.78 to 1.06; 5 studies, n=4 207), cardiovascular mortality (RR 0.90, 95% CI 0.74 to 1.11, 3 studies, n=4 070) and quality of life (MD 0.84, 95% CI -2.30 to 3.98; 3 studies, n=511) was observed. MRA treatment was associated with a greater risk of hyperkalaemia (RR 2.11, 95% CI 1.77 to 2.51; NNTH 11; 6 studies, n=4 291) compared to control.ACEI treatment had little or no effect on cardiovascular mortality (RR 0.93, 95% CI 0.61 to 1.42; 2 studies, n=954), all-cause mortality (RR 1.04, 95% CI 0.75 to 1.45; 5 studies, n=1 187), heart failure hospitalisation (RR 0.86, 95% CI 0.64 to 1.15; 3 studies, n=1 019), or quality of life (MD -0.09, 95% CI -3.66 to 3.48; 2 studies, n=154). The effects on hyperkalaemia were uncertain. ARBs had little or no effect on cardiovascular mortality (RR 1.02, 95% CI 0.90 to 1.14; 3 studies, n=7 254), all-cause mortality (RR 1.01, 95% CI 0.92 to 1.11; 4 studies, n=7 964), heart failure hospitalisation (RR 0.92, 95% CI 0.83 to 1.02; 3 studies, n=7 254), or quality of life (MD 0.41, 95% CI -0.86 to 1.67; 3 studies, n=3 117). ARB was associated with an increased risk of hyperkalaemia (RR 1.88, 95% CI 1.07 to 3.33; 2 studies, n=7 148).ARNIshad little or no effect on cardiovascular mortality (RR 0.96, 95% CI 0.79 to 1.15; 1 study, n=4 796), all-cause mortality (RR 0.97, 95% CI 0.84 to 1.11; 3 studies, n=7 663), or quality of life. ARNI compared to usual care resulted in a slight reduction in heart failure hospitalisation (RR 0.89, 95% CI 0.80 to 1.00; 2 studies, n=7 362). ARNI was associated with a reduced risk of hyperkalaemia (RR 0.88, 95% CI 0.77 to 1.01; 2 studies, n=5 054) compared to valsartan.

Clinical comments

Note

Date of latest search:

    References

    • Martin N, Manoharan K, Davies C et al. Beta-blockers and inhibitors of the renin-angiotensin aldosterone system for chronic heart failure with preserved ejection fraction. Cochrane Database Syst Rev 2021;(5):CD012721. [PubMed]

Primary/Secondary Keywords