Disparities In Socioeconomic Context And Response To Antihypertensive Medication In The Antihypertensive And Lipid-Lowering Treatment To Prevent Heart Attack Trial (allhat)

Where one lives affects one’s blood pressure. Observational studies demonstrate that living in communities of low socioeconomic status is associated with higher blood pressure and worse cardiovascular outcomes. In understanding the reasons for these disparities, a key question is whether evidence-based antihypertensive medication therapy is less effective in lowering blood pressure and improving cardiovascular outcomes in lower socioeconomic communities. If so, then anti-hypertensive therapies derived from randomized clinical trials (RCTs) may be suboptimal in achieving expected outcomes. Despite standardized protocols and balancing of demographic and clinical characteristics between study arms of RCTs, the socioeconomic environment in which people live is rarely examined, potentially exerting an unmeasured effect on study outcomes. To determine the impact of socioeconomic context on response to antihypertensive medication in clinical trials, we analyzed data from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), the largest existing RCT of hypertension treatment. This trial, conducted from 1994 to 2002, randomized 42,418 people, 55 years or older, with hypertension and at least one other cardiovascular risk factor, to chlorthalidone, lisinopril, amlodipine or doxazosin (mean follow-up of 4.9 years). After excluding non-continental U.S. sites and the doxazosin arm (terminated early in ALLHAT) our study included 27,862 participants. We defined socioeconomic context by mapping study site ZIP codes to counties and stratifying these counties into income quintiles based on the national distribution of county median household income, adjusted for cost-of-living, from the 2000 U.S. census. We compared baseline and clinical characteristics, visit and medication adherence, blood pressure control, and cardiovascular outcomes between ALLHAT participants in the lowest and highest income sites using multivariable regression models. Participants receiving care in Quintile 1 (Q1, lowest income sites) (n = 2169, 7.8%) were more likely to be female, black, Hispanic, have fewer total years of education, live in the South, and have fewer cardiovascular risk factors than participants in Quintile 5 (Q5, highest income sites) (n = 10458, 37.6%). Compared with Q5, participants in Q1 were less likely to achieve blood pressure control (\u3c140/90 mmHg) (OR, 0.48; 95% CI, 0.37- 0.63), and experienced higher all-cause mortality (HR, 1.25; 95% CI, 1.10-1.41), heart failure hospitalizations or mortality (HR, 1.26; 95% CI, 1.03-1.55) and end-stage renal disease (ESRD) (HR, 1.86; 95% CI, 1.26-2.73), though lower angina hospitalizations (HR, 0.70; 95% CI, 0.59-0.83) and coronary revascularization (HR, 0.71; 95% CI, 0.57- 0.89). There were no differences in stroke, myocardial infarction, or peripheral arterial disease. Despite having access to standardized treatment protocols, participants in the lowest income sites experienced poorer blood pressure control, higher mortality, ESRD and heart failure morbidity, and decreased coronary revascularization compared to those in the highest income sites. These findings suggest a need to better measure and bolster the socioeconomic context beyond the medical environment to eliminate disparities in outcomes for RCTs of antihypertensive medications. Understanding these relationships may guide the generalizability of RCT findings, promote the assessment of participants’ socioeconomic context in clinical trials and hypertension treatment guidelines, and inform broader strategies for combating hypertension in populations living in low socioeconomic environments