Management of Heart Failure in Special Populations
HF in African Americans
Clinical Characteristics and Prognosis. Cardiovascular disease is a major health issue for African Americans.30,62 Traditionally, concern has focused on hypertension and stroke as key components of the burden of cardiovascular disease in this population. However, HF represents a major source of cardiovascular morbidity and mortality for African Americans. Epidemiologic data suggests that they are at greater risk for HF than Caucasians, with approximately 3% of all African-American adults affected.
A number of clinical studies have documented substantial differences between the baseline clinical characteristics of African Americans and Caucasians with HF.33,34,49 Age of onset is significantly younger in blacks than in whites, and HF is less likely to be due to ischemic heart disease. Incident HF before 50 years of age is substantially more common among blacks than among whites. Hypertension, obesity, and systolic dysfunction that are present before a person is 35 years of age are important antecedents.63
Analysis of outcome data from the SOLVD trials has shown higher mortality and morbidity rates in blacks compared to whites with HF.64 Whether these differences reflect differences in baseline characteristics, delivery of care or socioeconomic factors has not been resolved. Other studies point to problems with access to care and unfavorable clinical characteristics independent of HF as factors increasing the risk of African Americans for worse outcomes.65-67
Aggressive, early treatment of hypertension has been proposed as a major strategy for the prevention of HF in this racial group. Persistent hypertension is not uncommon in African-American patients with HF and systolic dysfunction.
Treatment Response. Although a number of clinical characteristics have been shown to differ significantly between African Americans and other races afflicted with HF, the implications of these differences for therapy remain to be determined.
Recommendation
Beta blockers are recommended as part of standard therapy for African Americans with HF due to:
- symptomatic LV systolic dysfunction (Strength of Evidence = B)
- asymptomatic LV systolic dysfunction (Strength of Evidence = C)
Background
Although 1 trial with bucindolol did not find a beneficial effect of beta blockade in African Americans with HF,68 subgroup analysis of data from the US Carvedilol Trials suggests that the beneficial effect of beta blockers on outcomes in African Americans with HF from systolic dysfunction is similar to the effects in the larger population.69 Other studies demonstrate similar findings.21,50,70 The totality of the data supports substantial benefit from these agents, regardless of race.
Recommendations
ACE inhibitors are recommended as part of standard therapy for African-American patients with HF from symptomatic or asymptomatic LV systolic dysfunction. (Strength of Evidence = C)
ARBs are recommended as substitute therapy for HF in African Americans intolerant of ACE inhibitors. (Strength of Evidence = B)
Background
ACE Inhibition. Long-standing clinical experience suggests that African Americans with hypertension respond less well than Caucasians to ACE inhibitors.71 Concern has persisted that differences in the effectiveness of blockade of the RAAS in HF might be present between the 2 races as well. Recently, retrospective subgroup analysis of data from 2 randomized clinical trials has added support to the concept that the response of blacks and whites with HF and LV systolic dysfunction to ACE inhibition may differ. A reanalysis of the SOLVD Prevention and Treatment trials investigated the influence of race on the response to enalapril.72 Unadjusted analysis in the matched-cohort indicated that enalapril reduced the risk of hospitalization for HF in white patients by 44%, whereas no significant benefit was seen in black patients. Adjusted analysis confirmed a beneficial effect on hospitalization risk for Caucasians, but not for African Americans. At 1 year, enalapril therapy was associated with a significant reduction in both systolic blood pressure and diastolic blood pressure in Caucasian patients, whereas no significant reduction was observed in African-American patients.
It must be remembered that this study was a post-hoc subgroup analyses of randomized studies that were not stratified based on race. The SOLVD data raise the possibility that treatment response to ACE inhibition may vary between the races. However, they do not provide sufficient data to support a strategy other than routine use of ACE inhibitors in African Americans with HF.
Clinical studies have also shown that the risk of angioedema is greater in African American patients compared to Caucasians.73
Angiotensin-Receptor Blockade. The use of ARBs in African Americans with HF has not been well characterized in clinical trials. It would thus be reasonable in this population to follow the general recommendations for the use of ARBs (see Section 7).
Recommendation
A combination of hydralazine and isosorbide dinitrate is recommended as part of standard therapy in addition to beta blockers and ACE-inhibitors for African Americans with LV systolic dysfunction and:
- New York Heart Association (NYHA) class III or IV HF (Strength of Evidence = A)
- NYHA class II HF (Strength of Evidence = B)
Background
A strong recommendation now exists for the addition of the fixed combination of isosorbide dinitrate and hydralazine to the standard medical regimen for African Americans with HF. Data from the Vasodilator-Heart Failure Trial (VHeFT) I and II suggested that a racial difference in treatment response existed between white and black patients with symptomatic LV dysfunction treated with hydralazine-isosorbide dinitrate versus placebo or enalapril, respectively.74 The A-HeFT enrolled 1050 self-identified black patients who had NYHA class III or IV HF with dilated ventricles and systolic dysfunction.60 In this placebo-controlled, blinded, and randomized trial, subjects were randomly assigned to receive a fixed combination of isosorbide dinitrate plus hydralazine or placebo in addition to standard therapy for HF. The primary end point was a composite score made up of weighted values for death from any cause, a first hospitalization for HF, and change in the quality of life. The study was terminated early owing to a significantly higher mortality rate in the placebo group than in the group given the fixed combination of isosorbide dinitrate plus hydralazine. The mean primary composite score was significantly better in the group given isosorbide dinitrate plus hydralazine than in the placebo group, as were its individual components: 43% reduction in the rate of death from any cause, 33% relative reduction in the rate of first hospitalization for HF, and an improvement in the quality of life. A provocative retrospective analysis of the A-HeFT study suggests that fixed dose isorsorbide dinitrate and hydralazine have a mortality benefit in African-Americans in the absence of beta-blockers and ACE inhibitors, and that beta-blockers but not ACE inhibitors add significant additional mortality benefit.75
Other Medications. In the absence of data to the contrary, other HF medications, including diuretics, digoxin, and aldosterone antagonists should be considered as options for the African-American patient with HF.