The Acute Decompensated HEart failure national REgistry (ADHERE), in which the records of well over 80,000 Medicare patients were reviewed, found that more than 60% of those hospitalized with HFPEF had uncontrolled hypertension, with a systolic pressure >140 mm Hg; 21% had atrial fibrillation.2 These findings emphasize the importance of aggressive blood pressure (BP) and heart rate control.
Management of HFPEF is goal directed
The aim of pharmacologic treatment of HFPEF is to maintain fluid balance, prevent tachycardia, treat and prevent ischemia, and control hypertension (TABLE).14,17-30 While the use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and beta-blockers, among other pharmacologic agents, is well studied for patients with reduced EF, there is limited evidence to guide the treatment of those with HFPEF. Although no single agent or drug class has been shown to be superior for such patients, there are a number of pharmacologic treatments to consider.
TABLE
Management of heart failure with preserved ejection fraction—matching treatment and goals14,17-30
| Treatment goal | Modality |
|---|---|
| Reduce congestion | Diuretics Salt restriction |
| Maintain atrial contraction | A-V pacing Cardioversion |
| Prevent tachycardia | A-V pacing Beta-blockers Calcium channel blockers |
| Prevent/treat ischemia | Antiplatelet therapy Beta-blockers Calcium channel blockers Revascularization Statins |
| Control hypertension | Antihypertensive agents:
|
| Promote regression of LV remodeling | ACE inhibitors ARBs |
| Improve exercise capacity | Supervised exercise program |
| ACE, angiotensin-converting enzyme; ARBs, angiotensin receptor blockers; LV, left ventricle. | |
Inhibition of the renin-angiotensin-aldosterone system
Pathologic activation of the renin-angiotensin-aldosterone system (RAAS) contributes to elevated systolic and diastolic pressure, LV hypertrophy, and LV fibrosis. Inhibition of this system is a promising treatment modality for HFPEF.31
ACE inhibitors. Experimental studies suggest that ACE inhibitors benefit the diastolic properties of the heart, in both short- and long-term use. The PEP-CHF trial found that for older patients with diastolic dysfunction, perindopril led to significant improvements in functional class and exercise capacity but failed to show a statistically significant reduction in all-cause mortality or hospitalization for acute decompensated HF.17
ARBs. There is no evidence to show that ARB therapy improves morbidity or mortality in HFPEF. Using surrogate end points, ARBs have been associated with regression of LV hypertrophy, and losartan was found to improve exercise tolerance and quality of life, compared with hydrochlorothiazide.18,19 In the CHARM-Preserved trial, candesartan showed an insignificant reduction in cardiovascular mortality and hospitalization for HF.
These results must be viewed with caution, however, because adverse effects led to high rates of medication discontinuation.32 In the I-PRESERVE trial, irbesartan conferred no benefit with respect to mortality, hospitalization, or quality of life on patients with HFPEF.33
ACE inhibitor or ARB—not both. ACE inhibitors and ARBs are good choices for BP control in patients with HFPEF, especially if LV hypertrophy is present, but periodic testing of renal function and potassium levels is needed. ACE inhibitors and ARBs should not be used concurrently, as the combination increases the risk of acute renal failure and has no benefit in clinical outcomes.34
BP and rate control
In small trials, beta-blockers have been found to improve diastolic function as seen on echocardiography, but data on morbidity and mortality are lacking.20 A secondary analysis of the OPTIMIZE-HF registry found that beta-blocker therapy was associated with reduced mortality and readmission in patients with reduced EF, but not in those with normal EF.21
Findings from the SENIORS trial were more promising: Treatment with nebivolol reduced both mortality and readmission rates for elderly patients with HF, with similar benefits for those with reduced and preserved EF.22 Overall, beta-blockers appear to be a reasonable choice for heart rate and/or BP control in patients who have HFPEF and atrial fibrillation or hypertension. Carvedilol, long-acting metoprolol, and bisoprolol have been shown to reduce mortality in HF with reduced EF, and it is reasonable to choose one of these agents for patients with preserved EF, as well.23
Calcium channel blockers (CCBs) may be useful in treating patients with HFPEF for both BP and heart rate control, as well. Theoretically, CCBs may also improve the process of relaxation by altering intracellular calcium cycling during the contractile cycle in myocytes. This contrasts with the management of HF patients with reduced EF, for whom the use of nonselective CCBs such as diltiazem and verapamil may adversely affect contractility.
In small RCTs, verapamil has been found to improve HF symptoms and exercise tolerance in patients with HFPEF,24 but no evidence of improved outcomes or mortality rates with CCB use has been found.
Other pharmacologic options to consider
Aldosterone antagonist therapy is an important component of treatment for patients with HF with reduced EF. Data supporting the use of spironolactone use from the RALES trial and eplerenone in the EPHESUS and EMPHASIS-HF trials suggest a reduction in mortality in patients with low (<35%) LVEF.25-27 For patients with preserved EF, however, spironolactone is not generally recommended.