ACE Inhibitors and CV Outcomes in Patients on Hemodialysis
ACE Inhibitors and CV Outcomes in Patients on Hemodialysis
Background
Persons with end-stage renal disease (ESRD) on hemodialysis carry an exceptionally high burden of cardiovascular disease. Angiotensin-converting enzyme inhibitors (ACEIs) are recommended for patients on dialysis, but there are few data regarding their effectiveness in ESRD.
Methods
We conducted a secondary analysis of results of the HEMO study, a randomized trial of dialysis dose and membrane flux in patients on maintenance hemodialysis. We focused on the nonrandomized exposure of ACEI use, using proportional hazards regression and a propensity score analysis. The primary outcome was all-cause mortality. Secondary outcomes examined in the present analysis were cardiovascular hospitalization, heart failure hospitalization, and the composite outcomes of death or cardiovascular hospitalization and death or heart failure hospitalization.
Results
In multivariable-adjusted analyses, there were no significant associations among ACEI use and mortality (hazard ratio 0.97, 95% CI 0.82–1.14), cardiovascular hospitalization, and either composite outcome. Angiotensin-converting enzyme inhibitor use was associated with a higher risk of heart failure hospitalization (hazard ratio 1.41, 95% CI 1.11–1.80). In the propensity score–matched cohort, ACEI use was not significantly associated with any outcomes, including heart failure hospitalization.
Conclusions
In a well-characterized cohort of patients on maintenance hemodialysis, ACEI use was not significantly associated with mortality or cardiovascular morbidity. The higher risk of heart failure hospitalization associated with ACEI use may not only reflect residual confounding but also highlights gaps in evidence when applying treatments proven effective in the general population to patients with ESRD. Our results underscore the need for definitive trials in ESRD to inform the treatment of cardiovascular disease.
Angiotensin-converting enzyme inhibitors (ACEIs) have been shown to reduce mortality and cardiovascular morbidity in a variety of clinical scenarios, such as postacute myocardial infarction or in patients with heart failure or left ventricular dysfunction. Persons with end-stage renal disease (ESRD) on dialysis carry an exceptionally high burden of cardiovascular disease, with 45% of all deaths attributed to cardiovascular causes. Although current national clinical practice guidelines recommend the use of ACEIs in patients on maintenance dialysis, there are few data regarding their effectiveness for cardiovascular disease prevention in this population because randomized clinical trials of ACEIs systematically excluded patients with ESRD.
Given the uncertainty surrounding the effectiveness of ACEIs in patients on maintenance hemodialysis, we conducted a secondary analysis of data from the HEMO study. The HEMO study data have several advantages over previous observational studies, in that the data contain exceptionally detailed clinical information, allowing for improved case-mix adjustment, and clinical outcomes were rigorously adjudicated using standardized criteria rather than determined by administrative codes. We hypothesized that subjects receiving ACEIs at study entry would have lower risks of mortality and cardiovascular morbidity compared with subjects who did not receive this class of medication.
Abstract and Introduction
Abstract
Background
Persons with end-stage renal disease (ESRD) on hemodialysis carry an exceptionally high burden of cardiovascular disease. Angiotensin-converting enzyme inhibitors (ACEIs) are recommended for patients on dialysis, but there are few data regarding their effectiveness in ESRD.
Methods
We conducted a secondary analysis of results of the HEMO study, a randomized trial of dialysis dose and membrane flux in patients on maintenance hemodialysis. We focused on the nonrandomized exposure of ACEI use, using proportional hazards regression and a propensity score analysis. The primary outcome was all-cause mortality. Secondary outcomes examined in the present analysis were cardiovascular hospitalization, heart failure hospitalization, and the composite outcomes of death or cardiovascular hospitalization and death or heart failure hospitalization.
Results
In multivariable-adjusted analyses, there were no significant associations among ACEI use and mortality (hazard ratio 0.97, 95% CI 0.82–1.14), cardiovascular hospitalization, and either composite outcome. Angiotensin-converting enzyme inhibitor use was associated with a higher risk of heart failure hospitalization (hazard ratio 1.41, 95% CI 1.11–1.80). In the propensity score–matched cohort, ACEI use was not significantly associated with any outcomes, including heart failure hospitalization.
Conclusions
In a well-characterized cohort of patients on maintenance hemodialysis, ACEI use was not significantly associated with mortality or cardiovascular morbidity. The higher risk of heart failure hospitalization associated with ACEI use may not only reflect residual confounding but also highlights gaps in evidence when applying treatments proven effective in the general population to patients with ESRD. Our results underscore the need for definitive trials in ESRD to inform the treatment of cardiovascular disease.
Introduction
Angiotensin-converting enzyme inhibitors (ACEIs) have been shown to reduce mortality and cardiovascular morbidity in a variety of clinical scenarios, such as postacute myocardial infarction or in patients with heart failure or left ventricular dysfunction. Persons with end-stage renal disease (ESRD) on dialysis carry an exceptionally high burden of cardiovascular disease, with 45% of all deaths attributed to cardiovascular causes. Although current national clinical practice guidelines recommend the use of ACEIs in patients on maintenance dialysis, there are few data regarding their effectiveness for cardiovascular disease prevention in this population because randomized clinical trials of ACEIs systematically excluded patients with ESRD.
Given the uncertainty surrounding the effectiveness of ACEIs in patients on maintenance hemodialysis, we conducted a secondary analysis of data from the HEMO study. The HEMO study data have several advantages over previous observational studies, in that the data contain exceptionally detailed clinical information, allowing for improved case-mix adjustment, and clinical outcomes were rigorously adjudicated using standardized criteria rather than determined by administrative codes. We hypothesized that subjects receiving ACEIs at study entry would have lower risks of mortality and cardiovascular morbidity compared with subjects who did not receive this class of medication.
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