Impact of poor wealth distribution is similar to that of having a major comorbidity
Countries with the greatest disparities between the rich and poor generally have the worst heart failure outcomes, researchers reported.
A stepwise increase in combined cardiovascular deaths and heart failure hospitalizations was observed with increasing income inequality (as measured by the Gini coefficient) after adjusting for patient-level characteristics:
- Tertile 1 (lowest income inequality -- Central Europe, Scandinavian countries): 10.9 per 100 person-years (reference)
- Tertile 2 (intermediate income inequality -- North America, Australia, and India): 11.7 per 100 person-years (adjusted HR 1.03, 95% CI 0.95-1.11)
- Tertile 3 (highest income inequality -- South America, China): 13.7 per 100 person-years (adjusted HR 1.57, 95% CI 1.38-1.79)
The pattern stayed robust after further correction for societal characteristics and was similar for all-cause death, according to John McMurray, MD, of the British Heart Foundation Cardiovascular Research Centre at University of Glasgow, Scotland, and collaborators in the PARADIGM-HF and ATMOSPHERE trials, from which data for the analysis came.
Their study -- including more than 15,000 people in 54 countries -- was published online in JACC: Heart Failure.
"Greater income inequality was associated with worse heart failure outcomes, with an impact similar to those of major comorbidities," they concluded.
"The income inequality hypothesis states that an individual's health is affected not only by his or her own income but also by the distribution of income in that person's society, especially in high-income countries," the authors noted. "Among the psychosocial explanations, the one that is of most interest in heart failure is the belief that chronic stress as a consequence of the income inequality described above has detrimental psychoneuroendocrine effects."
ATMOSPHERE and PARADIGM-HF participants were adults with New York Heart Association functional class II to IV, left ventricular ejection fraction 35% or lower, who were taking an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker with a beta-blocker and a mineralocorticoid receptor antagonist.
Randomized to enalapril and/or aliskiren (Tekturna) or sacubitril/valsartan (Entresto), patients were followed for a median of 36.6 months and 27 months in ATMOSPHERE and PARADIGM-HF, respectively.
Individuals in tertile 3 countries (high income inequality) had the most events overall despite being the youngest and having a lower comorbidity burden. Their outcomes were noticeably worse than those in tertile 1 countries, where more smokers and heavy drinkers were located.
However, there was no significant continuous relationship between income inequality and heart failure hospitalization. The lowest risk belonged to the intermediate group rather than the group with least inequality, McMurray's group reported.
The overall population was highly selected, patients having been enrolled only after completing a run-in period taking both drug assignments, the authors acknowledged, and Africa was represented poorly.
"It is also unclear whether barriers or incentives to trial participation (and hence country-level representativeness of trial participants) varied with country income inequality," according to Stephen Greene, MD, and Robert Califf, MD, both of Duke University School of Medicine in Durham, North Carolina, in an accompanying editorial.
Citing the globalization of phase III heart failure trials in recent years, Greene and Califf wrote that the findings from McMurray's group have their "purest application" in future clinical trial design.
"The expansion of clinical trials into additional populations has been laudable, but sponsors may seek such environments for expediency to escape poor enrollment and high costs in North America and Western Europe, their primary markets," they wrote. "Globalization of clinical research can be a powerful social good, but we must understand and mitigate unintended consequences if we are to harness its full potential."
Troubles with "offshoring" trials surfaced with geographic differences observed in the TOPCAT trial data; those could be attributed to local investigator misconduct, researchers learned in 2017.
ATMOSPHERE and PARADIGM-HF were funded by Novartis.
McMurray disclosed no conflicts of interest.
Greene reported support from the National Heart, Lung, and Blood Institute; the Heart Failure Society of America; the Emergency Medicine Foundation; and research funding from Amgen and Novartis.
Califf was a previous FDA Commissioner; has served on the corporate board for Cytokinetics; has been the board chair for the People-Centered Research Foundation; has received consulting fees from Merck, Biogen, Genentech, Eli Lilly, and Boehringer Ingelheim; and is employed as a scientific advisor by Verily Life Sciences (Alphabet).
JACC: Heart Failure
Source Reference: Dewan P, et al "Income inequality and outcomes in heart failure: a global between-country analysis" JACC Heart Fail 2019; DOI: 10.1016/j.jchf.2018.11.005.
JACC: Heart Failure
Source Reference: Greene SJ, Califf RM "Reframing global variation in heart failure trials" JACC Heart Fail 2019; DOI: 10.1016/j.jchf.2018.12.012.
Read the original article on Medpage Today: Heart Failure Outcomes Worse Where Income Inequality Reigns