Bi Treatment With Hydralazine/Nitrates Versus Placebo in Africans Admitted With Acute Heart Failure
Bi Treatment With Hydralazine/Nitrates Versus Placebo in Africans Admitted With Acute Heart Failure
To investigate the effect of hydralazine isosorbide dinitrate on clinical outcomes, symptoms,
 cardiac parameters and functional status of African patients hospitalized with AHF and left
 ventricular dysfunction during 24 weeks of therapy.

 Administration of hydralazine/nitrates will be superior to placebo administration in reducing
 HF readmission or death, improving dyspnoea, reducing blood pressure and brain natriuretic
 peptide (BNP) in African patients admitted with AHF and left ventricular dysfunction.
Heart failure (HF) is a pathophysiologic condition and is a final common pathway of most
 forms of cardiovascular disease. Patients with HF experience poor quality of life, recurrent
 emergency hospitalizations and premature mortality.

 Recent publications highlight the multiple challenges of dealing with an increasing burden of
 heart disease within an urban African community. The predominance of women and novel
 underlying causes contrast with the demographic of HF in high income countries. More than 50%
 of 5328 de novo cases of heart disease captured at a tertiary clinic in Soweto presented with
 some form of heart failure, mainly due to poorly treated hypertension, idiopathic dilated
 cardiomyopathy, peripartum cardiomyopathy and HIV-related cardiomyopathy. The most prevalent
 form of heart disease was hypertensive heart failure (> 1100 cases).

 Programs have been developed in high income countries that cost-effectively prevent
 progressive cardiac dysfunction in high risk individuals and apply evidence-based treatments
 to optimize the overall management of HF. There is, however, a paucity of data describing the
 etiology and underlying cardiac structure and function, as well as contemporary management of
 HF in low to middle income countries.

 In 2005 a number of leading clinicians from Africa and the US published a "call for action"
 highlighting the need for an African study documenting the aetiology of acute heart failure
 and the management practices applied to these patients. As a result, The Sub-Saharan Africa
 Survey of Heart Failure (THESUS HF) study, was initiated in 9 countries in Africa to
 determine aetiology, treatment, morbidity and mortality of acute heart failure (HF) in the
 African sub-continent. The data reported in this study are unique as they are the first
 larger outcome study in acute heart failure from this continent. This first multinational
 study of over 1000 patients with acute decompensated heart failure conducted in all regions
 of sub-Saharan Africa shows, for the first time, that the treatment of heart failure is
 sub-optimal in the region, with relatively low proven medical treatments (such as
 beta-blockers, hydralazine and nitrates) and inappropriately high use of aspirin in a cohort
 of patients with non-ischaemic heart failure. This study also had the clear purpose of
 enhancing research capacity in Africa via collaborative research as outlined in our
 publication.

 The use of Ace inhibitors (ACEi) and hydralazine/nitrates has never been examined in patients
 admitted with acute heart failure. All studies demonstrating the beneficial effects of these
 drugs were performed in patients with chronic heart failure. Previous studies have shown that
 the administration of ACEi in African Americans with chronic heart failure is less effective
 and not superior to combined treatment with hydralazine/isosorbide dinitrate. The African
 American Heart Failure Trial (A-HeFT) established the benefit of adjunctive administration of
 isosorbide dinitrate/hydralazine (ISDN/HYD) in addition to standard therapy for African
 American patients with symptomatic heart failure. The risk of death was reduced by 33% and
 markers of quality of life were improved.

 The THESUS registry has shown a high prevalence of hypertension with left ventricular
 systolic dysfunction (hypertensive heart failure) and dilated cardiomyopathy as a cause of
 acute heart failure in all participating African countries. Patients in Africa are rarely
 treated with this combination therapy as the fixed combination (Bidil) is unavailable in
 Africa. There is uncertainty if the combination of hydralazine and isosorbide dinitrate,
 available as generic agents, is beneficial in Africans and many physicians in Africa are not
 aware of the outcome of those studies published in high impact factor journals, often not
 available to local doctors.

 Performing a multicentre study in Africa could confirm data obtained in African Americans,
 create awareness for this promising combination treatment and extend the use of the
 medication to patients with acute heart failure.

 This BAHEF protocol has an approved 'Amendment # 1' dated 29 April 2013. Amendments were
 changes to the Eligibility criteria and have been changed on this site.

 To date, 22 Sept 2014, the BAHEF study has enrolled 110 study subjects. To date, 13 Aug 2015,
 the BAHEF study has enrolled 145 eligible subjects.
Inclusion Criteria:

 1. > 18 years of age

 2. Hospital admission for acute heart failure as defined by the presence of acute dyspnea
 and the presence of clinical signs of heart failure on physical examination.

 3. Where available, NT-proBNP >900 pg/ml, >1800 pg/ml if the patient has atrial
 fibrillation at screening or >450 pg/ml if BMI > 35 kg/m2, LVEF <45% assessed by
 echocardiography or other method within the previous 12 months

 4. Background therapy with at least ACE-inhibitor or angiotensin receptor blocker (ARB)
 and beta-blocker (unless beta-blocker is contraindicated due to severe volume
 overload, low output heart failure, or cardiogenic shock)

 5. Available for regular follow up

 Exclusion Criteria:

 1. Currently being treated with Hydralazine and/or nitrates or a history of intolerance
 to oral therapy with either hydralazine or nitrates.

 2. . Any intravenous treatment for heart failure, except IV furosemide (eg. IV inotropes,
 pressors, nitrates or nesiritide) at the time of screening.

 3. Systolic blood pressure <100 mmHg

 4. Plan for revascularization

 5. Greater than 96 hours after admission

 6. Reversible etiology of acute heart failure such as myocarditis, acute myocardial
 infarction, arrhythmia. Acute MI is defined as symptoms and major electrocardiogram
 (ECG) changes(i.e., ST segment elevations), and arrhythmia includes unstable heart
 rates above 120/min or below 50/min.

 7. Hypertrophic obstructive cardiomyopathy, constrictive cardiomyopathy, endomyocardial
 fibroelastosis

 8. Known severe congenital heart disease (such as uncorrected tetralogy of fallot or
 transposition of the aorta)

 9. Severe aortic or mitral stenosis or severe rheumatic mitral regurgitation.

 10. Renal impairment (defined by creatinine >3 mg/dL) at screening or on any type of
 dialysis.

 11. Known hepatic impairment (total bilirubin >3mg/dl) or increased ammonia levels at
 screening.

 12. History of systemic lupus erythematous.

 13. Stroke or TIA within 2 weeks from screening.

 14. Women who are pregnant or lactating.

 15. Allergy to organic nitrates.

 16. History or presence of any other diseases (ie. Including malignancies or AIDS) with a
 life expectancy of < 12 months