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

Abstract

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.

Clinical Effectiveness of Hydralazine–Isosorbide Dinitrate in African-American Patients With Heart Failure

“…A prior study from the Get With The Guidelines-HF Registry linked to Medicare data did not find an observed benefit on all-cause mortality or readmissions for African Americans treated with H-ISDN (12). The sample size in that study was limited to 1,392 African American HF patients with a mean age of 75 years.…”

“…Furthermore, real-world clinical effectiveness of H-ISDN prescription has not been previously demonstrated (12). The Veterans Health Administration (VHA) is the largest integrated health system in the United States serving 8.76 million veterans (13).…”

Combination drug therapy in heart failure: greater than the sum of its parts

“…Clinical trials suggest that hydralazine–isosorbide dinitrate (H‐ISDN) may reduce cardiovascular morbidity and mortality among HFrEF patients who self‐identify as black or with documented intolerance and/or contraindications to ACEIs/ARBs . Despite the existing evidence, the available data suggest only approximately 20% of eligible patients are prescribed H‐ISDN at discharge, and adherence to this therapy post‐discharge is poor . Nevertheless, H‐ISDN should be strongly considered in select high‐risk populations including patients who self‐identify as black and continue to remain symptomatic and hypertensive despite optimal medical therapy as well as patients with advanced chronic kidney disease who are unlikely to tolerate treatment with an ARNI/ACEI/ARB and/or MRA.…”

Hydralazine and nitrates in the treatment of heart failure with reduced ejection fraction

“…The combination therapy resulted in 43% reduction in the rate of death from any cause (0.01) and 33% relative reduction in the rate of first heart failure hospitalization (0.001) and in an improvement in the quality of life (0.02). On the basis of the patients in the Get With The Guidelines -Heart Failure (GWTG-HF) registry, Khazanie et al 13 noted that amongst those older than 65 years with HFREF, 22.7% were Black and 18.2% had estimated Glomerular Filtration Rate (eGFR) < 30 mL/min/ 1.73 m 2 , the latter being a contraindication for the use of ACEi or ARB. 9 In their systemic review of the trials of hydralazine and nitrate combination in the treatment of HFREF, Farag et al, 10 concluded that the combination reduces the all-cause mortality and the cardiovascular mortality, but the evidence base suggests that the combination remained inferior to treatment with ACEi.…”

“…12 In the real world, two observational studies looked at the use of the combined hydralazine and nitrates in the treatment of patients with HFREF. On the basis of the patients in the Get With The Guidelines -Heart Failure (GWTG-HF) registry, Khazanie et al 13 noted that amongst those older than 65 years with HFREF, 22.7% were Black and 18.2% had estimated Glomerular Filtration Rate (eGFR) < 30 mL/min/ 1.73 m 2 , the latter being a contraindication for the use of ACEi or ARB. In these two groups of patients, the use of the combined hydralazine and nitrates was low, and the adherence to therapy was also low (46%).…”