Isosorbide dinitrate-hydralazine combination therapy in African Americans with heart failure

Despite significant improvement in therapy and management, heart failure remains a worrisome disease state that is especially problematic in special populations. African Americans suffer a disproportionately higher prevalence of heart failure when compared to other populations. It has been recently demonstrated that vasodilator therapy using the combination of isosorbide dinitrate (ISDN) and hydralazine (HYD) as an adjunct to background evidence-based therapy appears to display the strongest signal of benefit in reducing mortality and morbidity in the African American population. Through review of the retrospective and more recent prospective data, we will focus on the benefit of ISDN-HYD as adjunctive therapy for use in African Americans with systolic heart failure on concomitant appropriate evidence based therapy. This review also closely examines some of the potential contributions to endothelial dysfunction in African Americans, and the relationship of vascular homeostasis and nitric oxide. The role of oxidative stress in left ventricular dysfunction will also be explored as a reduction of oxidative stress offers particular promise in the management of heart failure. Although neurohormonal blockade has been responsible for notable event reductions in patients with systolic heart failure, the addition of ISDN-HYD, vasodilator therapy that enhances nitric oxide and reduces oxidative stress, further improves quality of life and survival in African American patients with heart failure. These findings strongly imply that nitric oxide enhancement and/or oxidative stress reduction may be important new therapeutic directions in the management of heart failure

Use of Hydralazine‐Isosorbide Dinitrate Combination in African American and Other Race/Ethnic Group Patients With Heart Failure and Reduced Left Ventricular Ejection Fraction

Background: Hydralazine‐isosorbide dinitrate (H‐ISDN) therapy is recommended for African American patients with moderate to severe heart failure with reduced ejection fraction (<40%) (HFrEF), but use, temporal trends, and clinical characteristics associated with H‐ISDN therapy in clinical practice are unknown. Methods and Results: An observational analysis of 54 622 patients admitted with HFrEF and discharged home from 207 hospitals participating in the Get With The Guidelines–Heart Failure registry from April 2008 to March 2012 was conducted to assess prescription, trends, and predictors of use of H‐ISDN among eligible patients. Among 11 185 African American patients eligible for H‐ISDN therapy, only 2500 (22.4%) received H‐ISDN therapy at discharge. In the overall eligible population, 5115 of 43 498 (12.6%) received H‐ISDN at discharge. Treatment rates increased over the study period from 16% to 24% among African Americans and from 10% to 13% among the entire HFrEF population. In a multivariable model, factors associated with H‐ISDN use among the entire cohort included younger age; male sex; African American/Hispanic ethnicity; and history of diabetes, hypertension, anemia, renal insufficiency, higher systolic blood pressure, and lower heart rate. In African American patients, these factors were similar; in addition, being uninsured was associated with lower use. Conclusions: Overall, few potentially eligible patients with HFrEF are treated with H‐ISDN, and among African‐Americans fewer than one‐fourth of eligible patients received guideline‐recommended H‐ISDN therapy. Improved ways to facilitate use of H‐ISDN therapy in African American patients with HFrEF are needed

Combination of Isosorbide Dinitrate and Hydralazine in Blacks with Heart Failure

BACKGROUND We examined whether a fixed dose of both isosorbide dinitrate and hydralazine provides additional benefit in blacks with advanced heart failure, a subgroup previously noted to have a favorable response to this therapy. METHODS A total of 1050 black patients who had New York Heart Association class III or IV heart failure with dilated ventricles were randomly assigned to receive a fixed dose ofisosorbide dinitrate plus hydralazine or placebo in addition to standard therapy for heart failure. The primary end point was a composite score made up of weighted values for death from any cause, a first hospitalization for heart failure, and change in the quality of life. RESULTS The study was terminated early owing to a significantly higher mortality rate in the placebo group than in the group given isosorbide dinitrate plus hydralazine (10.2 percent vs. 6.2 percent, P=0.02). The mean primary composite score was significantly better in the group given isosorbide dinitrate plus hydralazine than in the placebo group (-0.1±1.9 vs. -0.5±2.0, P=0.01; range of possible values, -6 to + 2), as were its individual components (43 percent reduction in the rate of death from any cause [hazard ratio, 0.57; P=0.01] 33 percent relative reduction in the rate of first hospitalization for heart failure [16.4 percent vs. 22.4 percent, P=0.001], and an improvement in the quality of life [change in score, -5.6±20.6 vs. -2.7±21.2, with lower scores indicating better quality of life; P=0.02; range of possible values, 0 to 105]). CONCLUSIONS The addition ofa fixed dose of isosorbide dinitrate plus hydralazine to standard therapy for heart failure including neurohormonal blockers is efficacious and increases survival among black patients with advanced heart failure

Gender differences in advanced heart failure: insights from the BEST study

OBJECTIVES: The goal of this study was to determine the influence of gender on baseline characteristics, response to treatment, and prognosis in patients with heart failure (HF) and impaired left ventricular ejection fraction (LVEF). BACKGROUND: Under-representation of women in HF clinical trials has limited our understanding of gender-related differences in patients with HF. METHODS: The impact of gender was assessed in the Beta-Blocker Evaluation of Survival Trial (BEST) which randomized 2,708 patients with New York Heart Association class III/IV and LVEF < or =0.35 to bucindolol versus placebo. Women (n = 593) were compared with men (n = 2,115). Mean follow-up period was two years. RESULTS: Significant differences in baseline clinical and laboratory characteristics were found. Women were younger, more likely to be black, had a higher prevalence of nonischemic etiology, higher right and left ventricular ejection fraction, higher heart rate, greater cardiothoracic ratio, higher prevalence of left bundle branch block, lower prevalence of atrial fibrillation, and lower plasma norepinephrine level. Ischemic etiology and measures of severity of HF were found to be predictors of prognosis in women and men. However, differences in the predictive values of various variables were noted; most notably, coronary artery disease and LVEF appear to be stronger predictors of prognosis in women. In the nonischemic patients, women had a significantly better survival rate compared with men. CONCLUSIONS: In HF patients with impaired LVEF, significant gender differences are present, and the prognostic predictive values of some variables vary in magnitude between women and men. The survival advantage of women is confined to patients with nonischemic etiology

Hospital Variation and Characteristics of Implantable Cardioverter-Defibrillator Use in Patients With Heart Failure Data From the GWTG-HF (Get With The Guidelines–Heart Failure) Registry

ObjectivesThe aim of this study was to describe hospital variation and factors associated with adherence to guidelines for implantable cardioverter-defibrillator (ICD) therapy.BackgroundStudies have shown incomplete application of ICD therapy in eligible heart failure (HF) patients.MethodsNew or discharge prescription rates for ICD therapy (ejection fraction ≤30% without documented ICD contraindications) for hospitals were calculated from participants in the GWTG-HF (Get With The Guidelines–Heart Failure) registry during January 2005 to June 2007. With hierarchical modeling, hospitals' patient case-mix adjusted ICD rate and hospital factors associated with ICD use were determined. The association of ICD rate and other quality of care indicators and procedure use was determined.ResultsOverall use of ICD in-hospital or planned implantation rate was 20%. This rate ranged widely among hospitals, from 1% among the lowest tertile to 35% among the top tertile (p < 0.01). After adjusting for patient case mix, independent hospital characteristics associated with higher ICD use were percutaneous coronary intervention, coronary artery bypass grafting, and heart transplant capability as well as larger hospital bed size (p < 0.01). Hospital Centers for Medicare and Medicaid Services/Joint Commission on the Accreditation of Healthcare Organizations performance measures (discharge instructions, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker use, smoking cessation; p ≥ 0.05) were similar across ICD, whereas higher ICD-rate hospitals had higher adherence to GWTG-HF performance measures (beta-blocker use, evidence-based beta-blocker use, aldosterone-antagonist, hydralazine/nitrate; p < 0.05) except warfarin in patients with atrial fibrillation (p = 0.18).ConclusionsThere is significant unexplained hospital variation in the use of ICD therapy among potentially eligible HF patients. However, hospitals that use ICD therapy more often also have more rapidly adopted other newer evidence-based HF therapies

Health Insurance and Cardiac Transplantation A Call for Reform

Cardiac transplantation is an accepted therapy for patients with end-stage heart failure (ESHF). Presently in the U.S., patients with ESHF need to have health insurance or another funding source to be considered eligible for cardiac transplantation. Whether it is appropriate to exclude potential recipients solely due to lack of finances has received considerable interest including being the subject of a recent major motion picture (John Q, New Line Cinema, 2002). However, one important aspect of this debate has been underappreciated and insufficiently addressed. Specifically, organ donation does not require the donor to have health insurance. Thus, individuals donate their hearts although they themselves would not have been eligible to receive a transplant had they needed one. By querying Siminoff’s National Study of Family Consent to Organ Donation database, we find that this situation is not uncommon as ∼23% of organ donors are uninsured. Herein we also discuss how the funding requirement for cardiac transplantation has been addressed by the federal government in the past, its implications on the organ donor consent process, and its potential impact on organ donation rates. We call for a government-sponsored, multidisciplinary task force to address this situation in hopes of remedying the inequities in the present system of organ allocation

Incremental Reduction in Risk of Death Associated with Use of Guideline-Recommended Therapies in Patients with Heart Failure: A Nested Case-Control Analysis of IMPROVE HF

Background: Several therapies are guideline-recommended to reduce mortality in patients with heart failure (HF) and reduced left ventricular ejection fraction, but the incremental clinical effectiveness of these therapies has not been well studied. We aimed to evaluate the individual and incremental benefits of guideline-recommended HF therapies associated with 24-month survival. Methods and results: We performed a nested case-control study of HF patients enrolled in IMPROVE HF. Cases were patients who died within 24 months and controls were patients who survived to 24 months, propensity-matched 1:2 for multiple prognostic variables. Logistic regression was performed, and the attributable mortality risk from incomplete application of each evidence-based therapy among eligible patients was calculated. A total of 1376 cases and 2752 matched controls were identified. β-Blocker and cardiac resynchronization therapy were associated with the greatest 24-month survival benefit (adjusted odds ratio for death 0.42, 95% confidence interval (CI), 0.34–0.52; and 0.44, 95% CI, 0.29–0.67, respectively). Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, implantable cardioverter-defibrillators, anticoagulation for atrial fibrillation, and HF education were also associated with benefit, whereas aldosterone antagonist use was not. Incremental benefits were observed with each successive therapy, plateauing once any 4 to 5 therapies were provided (adjusted odds ratio 0.31, 95% CI, 0.23–0.42 for 5 or more versus 0/1, P<0.0001). Conclusions: Individual, with a single exception, and incremental use of guideline-recommended therapies was associated with survival benefit, with a potential plateau at 4 to 5 therapies. These data provide further rationale to implement guideline-recommended HF therapies in the absence of contraindications to patients with HF and reduced left ventricular ejection fraction