Assessing the Cause of Race-Based Differences in Outcomes Observed in the PARADIGM-HF Trial

Black patients tend to develop heart failure at an earlier age and have distinctly worse outcomes than do non-black patients, as pointed out by Eldrin Foster Lewis, MD, MPH, director of the Cardiovascular Clerkship Program at Brigham and Women’s Hospital and assistant professor of medicine at Harvard Medical School, during a presentation at the 2016 Heat Failure Society of America annual meeting. Recent studies indicate higher hospitalization rates among black patients, but conversely, the actual rate of mortality was similar or reduced for black patients as compared to non-blacks.

This calls into question whether the results of clinical studies to date may be biased by baseline characteristics of the enrolled patients, or due to race-dependent variations in the response to medications. To address these possibilities, Lewis and colleagues searched for associations between heart failure/cardiovascular events/mortality and race. They analyzed data from the PARADIGM-HF trials, which randomized 8,399 heart failure (HF) patients for treatment with sacubitril/valsartan or enalapril. Only the characteristics of 428 self-described black patients and 5,544 self-described white patients were considered.

The researchers analyzed baseline characteristics of patients enrolled in PARADIGM-HF and found that black patients had a mild elevation in natriuretic peptides and (most interestingly) less atrial fibrillation. There were more women than men among this group, and these patients had a higher glomerular filtration rate (GFR). Despite the presence of these more favorable characteristics within the black patient cohort, researchers reported a lower ejection fraction and a higher incidence of primary outcome (cardiovascular death, heart failure hospitalization, and all-cause death) in black patients compared with non-blacks.

Subsequent Kaplan-Meier survival curve analysis revealed an early separation for all events with the exception of all-cause death; but even all-cause death had a significant difference, with lower survival rates among black patients. The impact of randomization of sacubitril/valsartan over enalapril was examined, and analysis determined the outcome to be the same with no significant interaction.

In conclusion, analysis revealed that self-described black patients had more favorable prognostic baseline characteristics than the white patients enrolled in the PARADIGM-HF study. Self-described black patients exhibited a higher risk for cardiovascular death and hospitalizations than white patients, but placebo-controlled randomized trials indicate a similar superior efficacy for sacubitril/valsartan over enalapril for both racial groups.

The presentation was well received and stimulated an active dialogue among a variety of researchers and physicians. During the discussion, the panel host asked if there was a way to get to the bottom of this. Lewis pointed out that while it is clear that there are disparate outcomes for black patients as compared to white patients, sometimes this is not evident within clinical trials. He stated that the best thing to do is to look at all of the heart failure hospitalization events and try to better understand the characteristics at the time of hospitalization. In the end, Lewis pointed out that differences in the mortality rates may be due to a tendency for lower threshold for hospitalization with non-blacks than with black patients. Accordingly, the entering non-black patient population may be a healthier cohort than hospitalized black patients.

Related Coverage:

Larry Allen, MD: Benefits of Shared Decision Making in Heart Failure Patients

Barry Borlaug, Mayo Clinic: Heart Failure With Preserved Ejection Fraction

Larry Allen, MD: The Rebirth in Heart Failure