Drugs for Chronic Heart Failure with Preserved Ejection Fraction

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.