Heart failure in African Americans: Disparities can be overcome

Hydralazine plus nitrates: Recommended for African Americans

Hydralazine plus isosorbide dinitrate (available as BiDil) is recommended as part of standard therapy, in addition to beta-blockers and ACE inhibitors specifically for African Americans with left ventricular systolic dysfunction and NYHA class III or IV heart failure (class I recommendation; level of evidence A), as well as NYHA class II heart failure (class I recommendation; level of evidence B).⁴¹

Preliminary evidence for this combination came from the Department of Veterans Affairs Cooperative Vasodilator-Heart Failure Trials.⁶⁶

Subsequently, the African-American Heart Failure Trial⁶⁷ was conducted in self-identified African American patients with NYHA class III or IV heart failure on standard heart failure therapy, including an ACE inhibitor if tolerated. Patients were randomly assigned to receive a fixed combination of isosorbide 20 mg and hydralazine 37.5 mg, one or two tablets three times a day, or placebo. The target dose of isosorbide dinitrate was 120 mg, and the target dose of hydralazine was 225 mg daily. Follow-up was up to 18 months. The study was terminated early because of a significant 43% improvement in overall survival for the patients in the isosorbide-hydralazine group. In addition, the rate of first hospitalization was 39% lower and the mean improvement in quality-of-life scores was 52% greater with isosorbide-hydralazine than with placebo.⁶⁷

There has been much debate about whether the benefit seen in this trial was the result of a hemodynamic effect, blood pressure response, or neurohormonal modulation. The benefit is less likely from a reduction in blood pressure, as the patients who had low blood pressure derived a mortality benefit similar to those with higher blood pressure, despite no further reduction in their blood pressure.⁶⁸

Treatment for heart failure with preserved ejection fraction

Although there are no data on how to manage heart failure with preserved ejection fraction that are specific to African Americans, the ACCF/AHA guideline⁴¹ recommends treating systolic and diastolic hypertension (class I, level of evidence B) according to published clinical practice guidelines and using diuretics to alleviate volume overload (class I; level of evidence C). Revascularization and management of atrial fibrillation are also “reasonable,” as are the use of ARBs, ACE inhibitors, and beta-blockers in the management of hypertension (class IIa; level of evidence C). ARBs may also be considered to reduce hospitalization in symptomatic patients with heart failure with preserved ejection fraction (class IIb, ie, “may be considered”; level of evidence B).

For acute decompensated heart failure

One of the greatest challenges in heart failure is treating patients who present with acute decompensated heart failure.

As in the general population, the major precipitating factor for hospitalization with decompensated heart failure in African Americans is nonadherence to prescribed dietary and medication regimens.³⁵ African Americans with acute decompensated heart failure tend to be younger and to have nonischemic cardiomyopathy, hypertension, diabetes, and obesity, but a lower risk of death.^35,69,70 Up to 44% have uncontrolled hypertension.³⁵

Inotropes and vasodilators have undergone multiple trials in the acutely decompensated state in the general population, but no trial has demonstrated a reduction in the mortality rate, and some showed a higher mortality rate. Thus, the treatment of acute decompensated heart failure remains primarily consensus-guided and symptom-focused.

Loop diuretics have been the mainstay in managing fluid retention and congestion in heart failure. The Diuretic Optimization Strategies Evaluation trial tested low-dose vs high-dose intravenous furosemide (Lasix) given either as a continuous infusion or as intermittent intravenous boluses. All strategies were safe and effective.⁷¹

Although ultrafiltration is an effective method of decongestion in heart failure and has been associated with a reduction in hospitalization, it is also associated with worsening renal function.⁷² The Cardiorenal Rescue Study in Acute Decompensated Heart Failure⁷³ compared ultrafiltration vs stepped diuretic therapy. In this trial, which enrolled approximately 26% nonwhites, stepped diuretic therapy was superior to ultrafiltration in preserving renal function in acute decompensated heart failure, although the efficacy of fluid removal was similar.

Both studies were small, and subgroup analyses are not likely to yield useful information. Nevertheless, these data support the use of intravenous diuretics, by continuous infusion or bolus, in acute decompensated heart failure.

Despite no benefit in terms of the mortality rate, inotropes continue to be used in some cases of acute decompensated heart failure, and African Americans appear to have a response to milrinone (Primacor IV) similar to that in whites.⁶⁹

In a nonrandomized study in which most patients were black, high-dose intravenous nitroglycerin appeared to be safe and associated with less need for ventilator support and intensive care unit admission, compared retrospectively with a population that did not receive high-dose nitroglycerin.⁷⁴

Given the different profile of the African American patient with acute decompensated heart failure, prospective studies would be useful in determining the best management strategy.

TREATMENTS FOR ADVANCED HEART FAILURE

Cardiac resynchronization and implantable cardioverter-defibrillators

Cardiac resynchronization therapy is indicated for patients with NYHA class II, III, and ambulatory class IV heart failure and left ventricular ejection fraction less than or equal to 35%, sinus rhythm, left bundle branch block, and a QRS duration greater than or equal to 150 ms (class I recommendation; level of evidence A for class NYHA III and IV; level of evidence B for NYHA class II).⁴¹

An implantable cardioverter-defibrillator is recommended in patients with NYHA class II or III heart failure for primary prevention of sudden cardiac death in selected patients with nonischemic dilated cardiomyopathy or ischemic heart disease (class I recommendation; level of evidence A).

However, few members of racial and ethnic minorities were included in trials of implantable cardioverter-defibrillators^75,76 or cardiac resynchronization,^7,77,78 so that subgroup analysis is limited. Use of an implantable cardioverter-defibrillator showed similar reduction in mortality between African Americans and whites, and compliance with device implantation and medical therapy was comparable.⁷⁹

Among patients discharged from hospitals in the American Heart Association’s Get With the Guidelines–Heart Failure Quality Improvement Program, fewer than 40% of potentially eligible patients received an implantable cardioverter-defibrillator, and rates were significantly lower for African Americans.⁸⁰ When they can get cardiac resynchronization therapy, African Americans appear to experience similar benefit from it.⁸¹