Which medications benefit patients with diastolic heart failure?

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Clinical Inquiries

Which medications benefit patients with diastolic heart failure?

J Fam Pract. 2011 February;60(2):101-108

By

Micah Crouse, MD

David Flack, DO

William J. Kerns, MD

Larisa Martin, MD

Daniel Pham, MD

Ramashilpa Sudireddy, MD

Karen Knight, MSLS

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References

1. Hunt SA, Abraham WT, Chin MH, et al. 2009 Focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in collaboration with the International Society for Heart and Lung Transplantation. J Am Coll Cardiol. 2009;53:e1-e90.

2. Tribouilloy C, Rusinaru D, Leborgne L, et al. Prognostic impact of angiotensin-converting enzyme inhibitor therapy in diastolic heart failure. Am J Cardiol. 2008;101:639-644.

3. Yusuf S, Pfeffer MA, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. Lancet. 2003;362:777-781.

4. Little WC, Zile MR, Klein A, et al. Effect of losartan and hydrochlorothiazide on exercise tolerance in exertional hypertension and left ventricular diastolic dysfunction. Am J Cardiol. 2006;98:383-385.

5. Warner JG Jr, Metzger DC, Kitzman DW, et al. Losartan improves exercise tolerance in patients with diastolic dysfunction and a hypertensive response to exercise. J Am Coll Cardiol. 1999;33:1567-1572.

6. Massie BM, Carson PE, McMurray JJ, et al. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med. 2008;359:2456-2467.

7. Aronow WS, Ahn C, Kronzon I. Effect of propranolol versus no propranolol on total mortality plus nonfatal myocardial infarction in older patients with prior myocardial infarction, congestive heart failure, and left ventricular ejection fraction ≥40% treated with diuretics plus angiotensin-converting enzyme inhibitors. Am J Cardiol. 1997;80:207-209.

8. Yip GW, Wang M, Wang T, et al. The Hong Kong diastolic heart failure study: a randomised controlled trial of diuretics, irbesartan and ramipril on quality of life, exercise capacity, left ventricular global and regional function in heart failure with a normal ejection fraction. Heart. 2008;94:573-580.

9. Fukuta H, Sane DC, Brucks S, et al. Statin therapy may be associated with lower mortality in patients with diastolic heart failure: a preliminary report. Circulation. 2005;112:357-363.

EVIDENCE-BASED ANSWER

Aangiotensin-converting enzyme inhibitors (ACEIs), propranolol, statins, furosemide, and some angiotensin receptor blockers (ARBs) benefit patients. Medications that reduce mortality in diastolic heart failure include ACEIs (strength of recommendation [SOR]: C, 1 prospective cohort trial with matched controls), propranolol (SOR: B, 1 randomized controlled trial [RCT]), and statins (SOR: C, 1 prospective cohort trial).

Furosemide improves symptoms of heart failure and quality of life (SOR: C, 1 RCT, using cohort data).

ARBs show mixed results: candesartan decreases hospital admissions (SOR: B, 1 large RCT); losartan improves exercise duration and quality of life (SOR: B, 2 small RCTs); irbesartan doesn’t improve heart failure symptoms or other outcomes (SOR: B, 1 large RCT).

Evidence summary

Diastolic heart failure, defined as classic evidence of congestive heart failure with “preserved” or “normal” left ventricular ejection fraction (LVEF),¹ is often encountered in medical practice. Unfortunately, studies that address diastolic heart failure don’t use a uniform ejection fraction to define preserved systolic function. Treatments for diastolic failure have included diuretics, ACEIs, ARBs, beta-blockers, calcium channel blockers, digoxin, and statins.

FAST TRACK

ACE inhibitors, propranolol, and statins reduce mortality in patients with diastolic heart failure.

ACEIs decrease mortality
One small prospective study in France enrolled 358 subjects who were admitted for a first episode of heart failure but had ejection fractions ≥50%. Patients were separated into 2 groups based on whether or not they were prescribed an ACEI—lisinopril (32.3%), ramipril (25.6%), perindopril (23.8%), or enalapril (5.5%)—at discharge. The authors attempted to adjust for selection bias by developing a propensity score and comparing matched controls.

Patients who had been prescribed ACEIs had a 10% reduction in 5-year mortality (number needed to treat [NNT]=10).²

ARBs produce mixed outcomes
Evidence regarding outcomes with ARBs is not clear cut. Candesartan was studied in the CHARM-Preserved Trial, which enrolled 3023 patients from 618 centers in 26 countries with New York Heart Association functional class II to class IV congestive heart failure of at least 4 weeks’ duration and LVEF >40%.³ The treatment group showed a significant decrease in hospital admission for congestive heart failure (NNT=30, covariate adjusted), but no improvement in mortality.

Evidence-based answers from the Family Physicians Inquiries Network

Which medications benefit patients with diastolic heart failure?

References

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