Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitor-Based Treatment on Cardiovascular Outcomes in Hypertensive Blacks Versus Whites

Abstract

Background: Clinical trial evidence suggests poorer outcomes in blacks compared with whites when treated with an angiotensin-converting enzyme (ACE) inhibitor-based regimen, but this has not been evaluated in clinical practice.

Objectives: This study evaluated the comparative effectiveness of an ACE inhibitor-based regimen on a composite outcome of all-cause mortality, stroke, and acute myocardial infarction (AMI) in hypertensive blacks compared with whites.

Methods: We conducted a retrospective cohort study of 434,646 patients in a municipal health care system. Four exposure groups (Black-ACE, Black-NoACE, White-ACE, White-NoACE) were created based on race and treatment exposure (ACE or NoACE). Risk of the composite outcome and its components was compared across treatment groups and race using weighted Cox proportional hazard models.

Results: Our analysis included 59,316 new users of ACE inhibitors, 47% of whom were black. Baseline characteristics were comparable for all groups after inverse probability weighting adjustment. For the composite outcome, the race treatment interaction was significant (p = 0.04); ACE use in blacks was associated with poorer cardiovascular outcomes (ACE vs. NoACE: 8.69% vs. 7.74%; p = 0.05) but not in whites (6.40% vs. 6.74%; p = 0.37). Similarly, the Black-ACE group had higher rates of AMI (0.46% vs. 0.26%; p = 0.04), stroke (2.43% vs. 1.93%; p = 0.05), and congestive heart failure (3.75% vs. 2.25%; p < 0.0001) than the Black-NoACE group. However, the Black-ACE group was no more likely to develop adverse effects than the White-ACE group.

Conclusions: ACE inhibitor-based therapy was associated with poorer cardiovascular outcomes in hypertensive blacks but not in whites. These findings confirm clinical trial evidence that hypertensive blacks have poorer outcomes than whites when treated with an ACE inhibitor-based regimen.

Keywords: antihypertensive medications; cardiovascular disease; electronic health record; race.

CENTRAL ILLUSTRATION. Hazard Ratios of Effects of ACE Inhibitor-based therapy versus NonACE-based therapy on CV outcomes in patients with hypertension

ACE inhibitor use was associated with poorer outcomes in blacks than in whites (8.7% vs. 6.40%). A comparison of the hazard ratios of blacks versus whites indicates that the relative risk for the composite outcome for blacks on ACE compared to NoACE was higher than the relative risk for whites on ACE compared to NoACE. The test for race treatment interaction was significant for the composite outcome with blacks having a higher event rate than whites (blacks versus whites; HR 1.18, 95% CI: 1.00–1.40, p <0.05). Black-ACE group experienced higher rates of AMI, stroke, and CHF compared to white-ACE group. Abbreviations: ACE = angiotensin-converting enzyme.

FIGURE 1. Relationship of Antihypertensive Medication Exposures to Cardiovascular Outcomes

This figure depicts the timeframe for study eligibility for adult hypertensive patients (age >18 years), who received care between January 1, 2004 and December 31, 2009; and who meet the following criteria: hypertension diagnosis (based on hypertension ICD-9 code on at least 2 clinic visits); and prescribed an ACE inhibitor, β-blockers, thiazide-type diuretics, or calcium channel blockers for at least 6 months after their first date of entry into the HHC system. Outcomes through December 31, 2009 were eligible for analysis.

FIGURE 2. Patient Flow Chart

The process used to select the final study sample for analyses. At baseline, 434,646 hypertensive patients met the initial study criteria, of which 359,499 met the second inclusion criteria including age and race. Of this, 275,217 were on one of the 4 study anthihypetensives for at least 6 months after their first date of entry into the HHC system. We eliminated patients who were prescribed ACE only once with no refill, and those with multiple duplicate visits, leaving a sample size of 76,546. Our final sample of 59,316 excluded additional patients including those with study outcomes of interest. AMI = acute myocardial infarction; ARB = angiotensin receptor blocker; CCB = calcium channel blocker; CHF = congestive heart failure; TTE = transthoracic echocardiography; other abbreviations as in Figure 1.