Combination of Isosorbide Dinitrate and Hydralazine in Blacks with Heart Failure

Taylor, Anne L.; Ziesche, Susan; Yancy, Clyde W.; Carson, Peter E.; D’Agostino, Ralph; Ferdinand, Keith C.; Taylor, Malcolm P.; Adams, Kirkwood F.; Sabolinski, Michael L.; Worcel, Manuel; Cohn, Jay N.

doi:10.1056/nejmoa042934

Cited by 1,540 publications

(561 citation statements)

References 62 publications

(94 reference statements)

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“…The obvious absence of the isosorbide dinitratehydralazine combination in any of our prescriptions requires mention. This combination demonstrated significant efficacy and survival advantage in African Americans in the A-HEFT study [9] ; and so was recommended for patients of African descent [1] . Reasons for ignoring this beneficial combination in our practice needs further study.…”

Section: Discussionmentioning

confidence: 99%

“…The evidence-based anti-HF classes are (a) ACEI/ ARB, (b) beta adrenergic blocker -BB, (c) aldosterone antagonist-AA, (d) cardiac glycoside-CG and (e) diuretic -DIUR [4][5][6][7][8][9] . However, the drug classes with survival-advantage are ACEI/ARB, BB and AA [4][5][6][7][8][9] . The flow-chart summary of ESC recommendations had suggested the following order for anti-HF drug classes: ACEI/ARB as foundation drug-class, + BB, + AA, + CG, with a comment that diuretic may be added if congestion was present [2] .…”

Section: Methodsmentioning

confidence: 99%

“…There is clear evidence from land-mark studies of disease-modulating and survival-promoting pharmacological treatment using ACEI [4,5] , ARB [6] , BB [7] AA [8] , and hydralazine/isosorbide-dinitrate combinations [9] . However, the take-up of some or all trial findings may be slow or incomplete [10][11][12] .…”

Section: Introductionmentioning

confidence: 99%

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Physician-adherence to pharmacotherapy guidelines for chronic heart failure in a tertiary health facility in Lagos, Nigeria

Ajuluchukwu

Emmanuel

Raji

2013

JHA

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Background: The increasing need for adherence evaluation of CHF amongst senior physicians in our environment prompted this study.Objective: To determine physician-adherence to pharmacotherapy guidelines in CHF in an economically resource-poor tertiary health facility. Methods:Review of prescription pattern of anti-CHF drug-class of 100 confirmed systolic-CHF patients was carried out. Data for adherence-evaluation were obtained from follow-up information from out-patient clinic-notes, while data on acute care medications and precipitating factors were from in-patient hospitalization notes.Results: CHF patients aged 54.7 ± 14.5 years, had NYHA III/IV symptoms (47%) and hypertension (61%). Anti-CHF pharmacotherapy averaged three drug-types; and consisted of ACEI/ARB (83%), β blockers-BB (48%), aldosterone antagonists (41%), CG (82%), and diuretics (75%). Adherence was assessed as good or complete in 50%, partial/ incomplete in 33%; but non-adherent in 17% of the total. While overall physician-adherence was 59.6% on single drug-classes, survival-advantage combinations with ACEI/ARB+BB and ACEI/ARB+BB+AA were present in 40% and 16% respectively. Older patients (≥ 65 years) had significantly lower prescriptions of all three classes of survival advantage anti-HF drugs, as follows: ACEI/ARB (56% versus 95%); BB (37.5% versus 52%); and AA (31% versus 63%) [p < .05].Conclusion: BB and AA were under-prescribed. Physician-adherence to evidence-based anti-HF drug classes was variable and influenced by patient's age. It was also comparable with reports from other countries. Our physicians will benefit from a structured HF education and feed-back program.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Physician-adherence to pharmacotherapy guidelines for chronic heart failure in a tertiary health facility in Lagos, Nigeria

Ajuluchukwu

Emmanuel

Raji

2013

JHA

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“…The African‐American Heart Failure Trial randomly assigned 1050 Black patients with NYHA III/IV HF on standard medical therapy (including ACE inhibitors) to hydralazine and ISDN versus placebo. There was a significant decrease in all‐cause mortality in the treatment arm ( P = 0.02) at 3 years (Taylor et al ., 2004). Despite the compelling data for the use of organic nitrates in HFrEF, the use of nitrates in HFpEF has been relatively untested until recently, with many clinicians prescribing them to increase exercise tolerance and activity levels.…”

Section: Evidence‐based Pharmacological Agentsmentioning

confidence: 99%

Present and future pharmacotherapeutic agents in heart failure: an evolving paradigm

Loudon

Noordali

Gollop

et al. 2016

British J Pharmacology

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Many conditions culminate in heart failure (HF), a multi‐organ systemic syndrome with an intrinsically poor prognosis. Pharmacotherapeutic agents that correct neurohormonal dysregulation and haemodynamic instability have occupied the forefront of developments within the treatment of HF in the past. Indeed, multiple trials aimed to validate these agents in the 1980s and early 1990s, resulting in a large and robust evidence‐base supporting their use clinically. An established treatment paradigm now exists for the treatment of HF with reduced ejection fraction (HFrEF), but there have been very few notable developments in recent years. HF remains a significant health concern with an increasing incidence as the population ages. We may indeed be entering the surgical era for HF treatment, but these therapies remain expensive and inaccessible to many. Newer pharmacotherapeutic agents are slowly emerging, many targeting alternative therapeutic pathways, but with mixed results. Metabolic modulation and manipulation of the nitrate/nitrite/nitric oxide pathway have shown promise and could provide the answers to fill the therapeutic gap between medical interventions and surgery, but further definitive trials are warranted. We review the significant evidence base behind the current medical treatments for HFrEF, the physiology of metabolic impairment in HF, and discuss two promising novel agents, perhexiline and nitrite.

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“…Subgroups have the potential to generate hypotheses for further prospective investigation; there is one such example in the heart failure discipline in which the combination of hydralazine and nitrates was determined to be effective in African Americans in the Vasodilator‐Heart Failure Trial (V‐HeFT),17 and subsequently this group was examined in the African–American Heart Failure Trial (A‐HeFT) 18. However there are also a significant number of examples in which subgroups led to additional negative studies, such as amlodipine in the elderly19 and amlodipine in patients with non‐ischemic cardiomyopathy20 or more commonly to no studies at all.…”

Section: Concluding Thoughtsmentioning

confidence: 99%

Subgroup analyses of randomized clinical trials in heart failure: facts and numbers

et al. 2016

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Subgroup analyses of major randomized clinical trials in heart failure are published frequently, but their impact on medical knowledge and practice guidelines has not been previously reported. In a novel analysis, we determined number of citations, impact factors, number of authors, and citations in guidelines of both parent trials and sub‐studies; we also qualitatively assessed whether the analyses were described as post‐hoc and non‐pre‐specified. A total of 229 sub‐studies evaluating outcomes in patient subgroups were published (median 6, range 0–36 per trial). The number of subjects in the parent trials positively correlated with number of sub‐studies (rho = 0.51, P = 0.009). The subgroups are frequently not pre‐specified. The impact factors of sub‐studies were lower in comparison to the parent trials as were the number of citations two years after the publication date; in addition, parent trials were cited more frequently in European and American professional guidelines compared with the sub‐studies. We maintain that the sub‐studies derived from major heart failure trials are frequently published, but their contribution to clinical guidelines and medical knowledge are highly debatable.

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Combination of Isosorbide Dinitrate and Hydralazine in Blacks with Heart Failure

Abstract: The addition of a 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.

Cited by 1,540 publications

References 62 publications

Physician-adherence to pharmacotherapy guidelines for chronic heart failure in a tertiary health facility in Lagos, Nigeria

Physician-adherence to pharmacotherapy guidelines for chronic heart failure in a tertiary health facility in Lagos, Nigeria

Present and future pharmacotherapeutic agents in heart failure: an evolving paradigm

Subgroup analyses of randomized clinical trials in heart failure: facts and numbers

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