Angiotensin receptor blockers and angiotensin-converting enzyme inhibitors: challenges in comparative effectiveness using Medicare data

Abstract

An evidence gap exists in comparing the effectiveness of angiotensin receptor II blockers (ARBs) for hypertension with that of angiotensin-converting enzyme inhibitors (ACEIs). We identified elderly hypertensive patients in whom ACEI/ARB therapy had been initiated after hospitalization for coronary artery disease (CAD), heart failure (HF), or stroke and who were eligible for Medicare and state pharmacy assistance programs. Of 18,801 initiators of ACEIs and 2,641 initiators of ARBs, 2,535 died during the follow-up. We observed substantial differences in characteristics between ARB and ACEI initiators, suggesting that ARB users were more health seeking. The incidence of death and sudden cardiac death (SCD) in ACEI initiators was 77 and 22 per 1,000 person-years, respectively. The relative risk for SCD comparing ARB initiators to ACEI initiators was 0.69 (95% confidence interval (CI) 0.50-0.96); when the analysis was restricted to patients with low ejection fraction (EF), the relative risk was 1.1. The reduced risk of SCD can be explained, at least partly, by (i) residual confounding because ARB users were healthier on unobserved domains and (ii) lack of data on EF.

Figure 1

Comparative Effectiveness of ARB vs. ACEI (Adjusted Hazard Ratios) on Selected Outcomes in Subgroups of Patients Defined by Gender, Race, Age, and Comorbidities among All Patients (The CAD, HF, and Stroke Cohorts Combined)

Figure 2

Sensitivity Analyses Assessing the Impact of Ejection Fraction on Sudden Cardiac Death Outcome. The HR comparing ARBs to ACEIs was fixed at 0.30 (green line), 0.51 (pink line), and 0.86 (dark blue line) (the point estimate and upper and lower 95% CI for the observed HR in HF cohort). The risk ratio between low EF (<45%) vs. high EF (>=45%) and SCD was assumed to be 2.5. The prevalence of low EF was fixed at 60% in the ACEI group and varied from 1% to 100% in ARB group. When the observed HR was 0.51, a large imbalance in the prevalence of low EF between ARB and ACEI group (60% difference in the actual prevalence) is needed for the corrected HR to be close to the null. When the observed HR was 0.86, less than 15 % difference in the prevalence of low EF in the two groups was necessary for the corrected HF to be 1(the null).

Figure 1

Comparative Effectiveness of ARB vs. ACEI (Adjusted Hazard Ratios) on Selected Outcomes in Subgroups of Patients Defined by Gender, Race, Age, and Comorbidities among All Patients (The CAD, HF, and Stroke Cohorts Combined)

Figure 2

Sensitivity Analyses Assessing the Impact of Ejection Fraction on Sudden Cardiac Death Outcome. The HR comparing ARBs to ACEIs was fixed at 0.30 (green line), 0.51 (pink line), and 0.86 (dark blue line) (the point estimate and upper and lower 95% CI for the observed HR in HF cohort). The risk ratio between low EF (<45%) vs. high EF (>=45%) and SCD was assumed to be 2.5. The prevalence of low EF was fixed at 60% in the ACEI group and varied from 1% to 100% in ARB group. When the observed HR was 0.51, a large imbalance in the prevalence of low EF between ARB and ACEI group (60% difference in the actual prevalence) is needed for the corrected HR to be close to the null. When the observed HR was 0.86, less than 15 % difference in the prevalence of low EF in the two groups was necessary for the corrected HF to be 1(the null).