Fixed-Dose vs. Off-Label Combos Compared in Black Patients with Heart Failure

The fixed dose combination was the first FDA-approved drug to treat a certain disease in a specific race.
The fixed dose combination was the first FDA-approved drug to treat a certain disease in a specific race.

Is there a difference between a fixed-dose combination of isosorbide dinitrate plus hydralazine HCl (FDC-ISDN/HYD) compared to an off-label combination of the separate generic drugs for the treatment of heart failure in African American patients? A retrospective study published in Advances in Therapy found a "genuine difference" between these treatments.

The Food and Drug Administration (FDA) approved FDC-ISDN/HYD as a new treatment based on clinical data from the African-American Heart Failure Trial; no therapeutic equivalent is currently available. This was the first FDA-approved drug to treat a certain disease in a specific race. 

ISDN was previously approved for the treatment of angina pectoris due to coronary artery disease, and HYD was approved for the treatment of hypertension. Off-label uses of the separate ingredients ISDN and HYD (OLC-ISDN+HYD) or isosorbide mononitrate (ISMN) and HYD (OLC-ISMN+HYD) are commonly substituted without supportive outcomes data.

Study authors performed an exploratory propensity-matched cohort study using Medicare data to assess overall survival differences between these treatments in patients with at least 80% 1-year medication adherence levels. African-American Medicare enrollees with heart failure were matched with Medicare Part D data to identify patients with prescriptions to FDC-ISDN/HYD or the off-label combinations; two sets of matched cohort pairs (each with FDC-ISDN/HYD and one off-label combo) were analyzed.  

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The study population had an average age of 77 years with a high occurrence of comorbidities. In the first set of matched cohorts, the Kaplan-Meier 1-year survival curves showed 87.9% (95% CI: 85.6–89.9) for FDC-ISDN/HYD and 83.0% (95% CI: 80.3–85.3) for OLC-ISDN+HYD (P=0.0024). In the second set, the FDC-ISDN/HYD and OLC-ISMN+HYD matched cohorts demonstrated 88.2% (95% IC: 85.9–90.2) and 84.8% (95% CI: 82.2–87.0%) 1-year survival rates (P=0.0320).

The data points to a noticeable difference in 1-year survival advantage for FDC-ISDN/HYD vs. off-label combinations among black Medicare patients with heart failure. The authors concluded that, "Despite the limitations of the Medicare databases, they can provide useful signals about the patterns and variations in care that African Americans with HF [heart failure] do or do not receive."

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