Hydralazine and Isosorbide Dinitrate in Heart Failure

Cole, Robert T.; Καλογερόπουλος, Ανδρέας; Georgiopoulou, Vasiliki V.; Gheorghiade, Mihai; Quyyumi, Arshed A; Yancy, Clyde W.; Butler, Javed

doi:10.1161/circulationaha.110.012781

Cited by 79 publications

(18 citation statements)

References 127 publications

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“…Whereas a fixed combination of H-ISDN was used in A-HeFT, patients in clinical practice commonly receive individual generic formulations at different doses. 22 The cost of a nongeneric fixed-dose combination of H-ISDN and interactions with other drugs such as erectile dysfunction medications may limit its use in practice. Some studies have suggested that generic formulations of H-ISDN are not bioequivalent to the fixed-dose combination.…”

Section: Discussionmentioning

confidence: 99%

Clinical Effectiveness of Hydralazine–Isosorbide Dinitrate Therapy in Patients With Heart Failure and Reduced Ejection Fraction: Findings From the Get With The Guidelines-Heart Failure Registry

Khazanie

Curtis

et al. 2016

Circ: Heart Failure

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Background In clinical trials, hydralazine-isosorbide dinitrate (H-ISDN) for heart failure with reduced ejection fraction reduced morbidity and mortality among black patients and patients with intolerance to angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). The effectiveness of H-ISDN in clinical practice is unknown. Methods and Results Using data from a clinical registry linked with Medicare claims, we examined the use and outcomes of H-ISDN between 2005 and 2011 among older patients hospitalized with heart failure and reduced ejection fraction. We adjusted for demographic and clinical characteristics using Cox proportional hazards models and inverse probability weighting. Among 4663 eligible patients, 22.7% of black patients and 18.2% of patients not on an ACE inhibitor or ARB were newly prescribed H-ISDN therapy at discharge. By 3 years, the cumulative incidence rates of mortality and readmission were similar between treated and untreated patients. After multivariable adjustment, 3-year outcomes remained similar for mortality (black patients: hazard ratio [HR], 0.92; 95% CI, 0.75–1.13; other patients: HR, 0.93; 95% CI, 0.79–1.09), all-cause readmission (black patients: HR, 0.98; 95% CI, 0.84–1.13; other patients: HR, 1.02; 95% CI, 0.90–1.17), and cardiovascular readmission (black patients: HR, 0.99; 95% CI, 0.82–1.19; other patients: HR, 0.94; 95% CI, 0.81–1.09). A post hoc analysis of Medicare Part D data revealed low postdischarge adherence to therapy. Conclusions Guideline-recommended initiation of H-ISDN therapy at hospital discharge was uncommon and adherence was low. For both black patients and patients of other races, there were no differences in outcomes between those treated and untreated at discharge.

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Section: Discussionmentioning

confidence: 99%

Clinical Effectiveness of Hydralazine–Isosorbide Dinitrate Therapy in Patients With Heart Failure and Reduced Ejection Fraction: Findings From the Get With The Guidelines-Heart Failure Registry

Khazanie

Curtis

et al. 2016

Circ: Heart Failure

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“…When the vasodilating combinations of a nitrate and hydralazine were prescribed in NYHA class III/IV, 1050 black patients showed significantly improved survival (43 percent reduction in the rate of death from any cause [hazard ratio, 0.57; P=0.01). These findings were not reproduced with prazosin and in other races [76]. On the contrary, the Australian Aboriginal population suffers from very high risks of CHF and renal impairment.…”

Section: Therapeuticsmentioning

confidence: 99%

Chronic Heart Failure and Comorbid Renal Dysfunction - A Focus on Type 2 Cardiorenal Syndrome

Jois

Mebazaa

Iyngkaran

et al. 2016

CCR

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The most important advancements in the Cardiorenal syndrome (CRS) are its definition and subsequent classifications. When the predominant pathology and pathophysiology is the heart, i.e. chronic heart failure (CHF), and where any renal impairment (RI) subsequent to this is secondary, the classification is type 2 CRS. There are unique differences in the pathophysiology and progression of individual subclasses. It is important to understand the evolution of CHF and consequences of subsequent RI as they are becoming increasingly prevalent, aggravate morbidity and mortality and limit many therapeutic options. In this paper we discuss the significance of the type 2 CRS patients in the context of the thematic series.

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“…The intended therapeutic consequence of improved tissue perfusion has the potential to recover end-organ function and some of the clinical deficits. The underlying idea of our therapeutic approach is similar to strategies that employ any combination of angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, hydralazine and nitrates to enhance vasodilation and, hence, tissue perfusion [11,67,68]. The primary advantage of our therapeutic approach lies in its specificity; it directly translates the mechanistic knowledge on TNF-α-driven myogenic S1P signaling and its effect on tissue perfusion in HF to specifically target this response and to modulate its strength with full preservation of autoregulatory function.…”

Section: The Translational Perspectivementioning

confidence: 99%

The TNF-α/Sphingosine-1-Phosphate Signaling Axis Drives Myogenic Responsiveness in Heart Failure

Kroetsch

Bolz²

2013

J Vasc Res

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Heart failure (HF) is hallmarked by an increase in total peripheral resistance (TPR) that compensates for the drop in cardiac output. While initially allowing for the maintenance of mean arterial pressure at acceptable levels, the long-term upregulation of TPR is prone to compromise cardiac performance and tissue perfusion, and to ultimately accelerate disease progression. Augmented vasoconstriction of terminal arteries, the site of TPR regulation, is cooperatively driven by mechanisms such as: (i) endothelial dysfunction, (ii) increased sympathetic activity and (iii) enhanced pressure-induced myogenic responsiveness. Herein, we review emerging evidence that the increase in myogenic responsiveness is central to the long-term elevation of TPR in HF. On a molecular level, this augmented intrinsic response is governed by an activation of the tumor necrosis factor-α (TNF-α)/sphingosine-1-phosphate signaling axis in microvascular smooth muscle cells. The beneficial effect of TNF-α scavenging strategies on tissue perfusion in HF mouse models adds to the gaining momentum to revisit the use of anti-TNF-α treatment modalities in discrete HF patient populations.

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Hydralazine and Isosorbide Dinitrate in Heart Failure

Cited by 79 publications

References 127 publications

Clinical Effectiveness of Hydralazine–Isosorbide Dinitrate Therapy in Patients With Heart Failure and Reduced Ejection Fraction: Findings From the Get With The Guidelines-Heart Failure Registry

Clinical Effectiveness of Hydralazine–Isosorbide Dinitrate Therapy in Patients With Heart Failure and Reduced Ejection Fraction: Findings From the Get With The Guidelines-Heart Failure Registry

Chronic Heart Failure and Comorbid Renal Dysfunction - A Focus on Type 2 Cardiorenal Syndrome

The TNF-α/Sphingosine-1-Phosphate Signaling Axis Drives Myogenic Responsiveness in Heart Failure

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