Cochrane for Clinicians

Putting Evidence into Practice

Medication Management for Chronic Heart Failure with Preserved Ejection Fraction

 

Am Fam Physician. 2019 Jul 1;100(1):17-19.

Author disclosure: No relevant financial affiliations.

Clinical Question

Do therapies that help patients who have heart failure with reduced ejection fraction (HFrEF) also improve morbidity and mortality in patients who have heart failure with preserved ejection fraction (HFpEF)?

Evidence-Based Answer

Mineralocorticoid receptor antagonists reduce hospitalizations for patients with HFpEF. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have not been shown to change the morbidity or mortality in patients with HFpEF. Beta blockers may positively affect cardiovascular mortality, but they do not improve hospitalizations or all-cause mortality.1 (Strength of Recommendation: A, based on consistent, good-quality patient-oriented evidence.)

Practice Pointers

HFpEF is a heterogeneous clinical syndrome with signs and symptoms of heart failure with left ventricular ejection fraction greater than 40%.2 Six million adults in the United States have heart failure.3 Patients with HFpEF account for one-half of this population and share similar mortality rates as those with HFrEF.1,4 The authors of this Cochrane review sought to determine if therapies that improve morbidity and mortality in patients with HFrEF (i.e., beta blockers, mineralocorticoid receptor antagonists, ACE inhibitors, and ARBs) have similar benefits in those with HFpEF.1

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SUMMARY TABLE:

TREATMENTS FOR CHRONIC HEART FAILURE WITH PRESERVED EJECTION FRACTION

OutcomesAssumed riskCorresponding risk (95% CI)ARR (95% CI)NNT (95% CI)

Angiotensin-converting enzyme inhibitors

Cardiovascular mortality

86 per 1,000

81 per 1,000 (53 to 123)

NA

NA

Heart failure hospitalization

13 per 1,000

11 per 1,000 (8 to 15)

NA

NA

Angiotensin receptor blockers

All-cause mortality

72 per 1,000

73 per 1,000 (66 to 80)

NA

NA

Cardiovascular mortality

131 per 1,000

133 per 1,000 (118 to 149)

NA

NA

Heart failure hospitalization

171 per 1,000

157 per 1,000 (142 to 174)

NA

NA

Beta blockers

All-cause mortality

243 per 1,000

199 per 1,000 (163 to 243)

NA

NA

Cardiovascular mortality

173 per 1,000

135 per 1,000 (107 to 171)

0.038 (0.002 to 0.066)

26 (15 to 500)

Heart failure hospitalization

117 per 1,000

86 per 1,000 (55 to 133)

NA

NA

Mineralocorticoid receptor antagonists

All-cause mortality

133 per 1,000

121 per 1,000 (104 to 141)

NA

NA

Cardiovascular mortality

88 per 1,000

79 per 1,000 (65 to 97)

NA

NA

Heart failure hospitalization

136 per 1,000

112 per 1,000 (94 to 134)

0.024 (0.002 to 0.042)

42 (23 to 500)


ARR = absolute risk reduction; NA = not applicable; NNT = number needed to treat.

SUMMARY TABLE:

TREATMENTS FOR CHRONIC HEART FAILURE WITH PRESERVED EJECTION FRACTION

OutcomesAssumed riskCorresponding risk (95% CI)ARR (95% CI)NNT (95% CI)

Angiotensin-converting enzyme inhibitors

Cardiovascular mortality

86 per 1,000

81 per 1,000 (53 to 123)

NA

NA

Heart failure hospitalization

13 per 1,000

11 per 1,000 (8 to 15)

NA

NA

Angiotensin receptor blockers

All-cause mortality

72 per 1,000

73 per 1,000 (66 to 80)

NA

NA

Cardiovascular mortality

131 per 1,000

133 per 1,000 (118 to 149)

NA

NA

Heart failure hospitalization

171 per 1,000

157 per 1,000 (142 to 174)

NA

NA

Beta blockers

All-cause mortality

243 per 1,000

199 per 1,000 (163 to 243)

NA

NA

Cardiovascular mortality

173 per 1,000

135 per 1,000 (107 to 171)

0.038 (0.002 to 0.066)

26 (15 to 500)

Heart failure hospitalization

117 per 1,000

86 per 1,000 (55 to 133)

NA

NA

Mineralocorticoid receptor antagonists

All-cause mortality

133 per 1,000

121 per 1,000 (104 to 141)

NA

NA

Cardiovascular mortality

88 per 1,000

79 per 1,000 (65 to 97)

NA

NA

Heart failure hospitalization

136 per 1,000

112 per 1,000 (94 to 134)

0.024 (0.002 to 0.042)

42 (23 to 500)


ARR = absolute risk reduction; NA = not applicable; NNT = number needed to treat.

This review included 37 randomized controlled trials with 18,311 patients. Primary outcomes were cardiovascular mortality and heart failure hospitalization, and secondary outcomes included all-cause mortality and quality of life. A limitation of this review was that a range of left ventricular ejection fraction cutoffs were used for HFpEF diagnosis (between 40% and 50%).

Beta blockers (i.e., carvedilol [Coreg], nebivolol [Bystolic], propranolol, metoprolol succinate, and bisoprolol) were compared with placebo in five studies and with usual care in five studies for a total of 3,087 patients. None of these studies were conducted in the United States or Canada. Only a few studies were included in the meta-analysis because of different outcome measures reported. There was an apparent reduction in cardiovascular mortality when examining the data across three studies (absolute risk reduction [ARR] = 0.038; 95% CI, 0.002 to 0.066; number needed to treat [NNT] = 26). However, the authors were cautious about drawing conclusions from this because when they removed the two studies that were considered to be at high risk of bias, the one remaining low-risk study did not demonstrate a difference in cardiovascular mortality between outcomes with beta blockers and placebo (relative risk = 0.81;

Author disclosure: No relevant financial affiliations.

References

show all references

1. Martin N, Manoharan K, Thomas J, Davies C, Lumbers RT. Beta-blockers and inhibitors of the renin-angiotensin aldosterone system for chronic heart failure with preserved ejection fraction. Cochrane Database Syst Rev. 2018;(6):CD012721....

2. 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. Heart. 2018;104:407–415.

3. Centers for Disease Control and Prevention. Heart failure fact sheet. https://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_heart_failure.htm. Accessed September 7, 2018.

4. Edelmann F, Wachter R, Schmidt AG, et al. Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved ejection fraction: the Aldo-DHF randomized controlled trial. JAMA. 2013;309(8):781–791.

5. Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017;136:e137–161.

These are summaries of reviews from the Cochrane Library.

This series is coordinated by Corey D. Fogleman, MD, Assistant Medical Editor.

A collection of Cochrane for Clinicians published in AFP is available at https://www.aafp.org/afp/cochrane.

 

 

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