Effect of Angiotensin Receptor Blockers on Cardiovascular Events in Patients Undergoing Hemodialysis: An Open-Label Randomized Controlled Trial
Received 12 July 2007; accepted 11 April 2008. published online 25 July 2008.
Refers to article:
Improving Outcomes in Hemodialysis Patients: The Need for Well-Designed Clinical Trials
Robert D. Toto
American Journal of Kidney Diseases
September 2008 (Vol. 52, Issue 3, Pages 400-402) Full Text |
Full-Text PDF (58 KB)
Background
Cardiovascular disease is the leading cause of mortality in patients with kidney failure treated with hemodialysis (HD). Although angiotensin receptor blockers (ARBs) reduce cardiovascular disease (CVD) events in patients with diabetes and chronic kidney disease, their effect in patients with kidney failure on HD therapy is not known.
Study Design
Open-labeled randomized trial.
Setting & Participants
Patients aged 30 to 80 years receiving HD 2 to 3 times weekly for 1 to 5 years at 5 university-affiliated dialysis centers.
Interventions
Treatment with ARBs (valsartan, candesartan, and losartan) versus without ARBs after stratification by sex, age, systolic blood pressure, and diabetes.
Outcomes
The primary end point is the development of fatal and nonfatal CVD events, defined as the composite of CVD death, myocardial infarction, stroke, congestive heart failure, coronary artery bypass grafting, or percutaneous coronary intervention. The secondary end point is all-cause death.
Results
366 subjects initially were randomly assigned to an ARB or no ARB (control), but after a run-in phase, 180 were retained in each group. Mean age was 60 years, 59% were men, 51% had diabetes, and mean predialysis systolic blood pressure was 154 mm Hg. There were 93 fatal or nonfatal CVD events (52%); 34 (19%) in the ARB group and 59 (33%) in the non-ARB group. After adjustment for age, sex, diabetes, systolic blood pressure, and center, treatment with an ARB was independently associated with reduced fatal and nonfatal CVD events (hazard ratio, 0.51; 95% confidence interval, 0.33 to 0.79; P = 0.002). There were 63 deaths (35%); 25 (14%) in the ARB group and 38 (21%) in the non-ARB group. After adjustment, all-cause mortality differed between the 2 groups (hazard ratio, 0.64; 95% confidence interval, 0.39 to 1.06; P = 0.1).
Limitations
Because of the small sample size of this trial, the large effect may be a spurious finding. Use of an open-label design and 3 different agents in the ARB group might have influenced results.
Conclusion
Use of an ARB may be effective in reducing nonfatal CVD events in patients undergoing long-term HD. A larger study is required to confirm these results.
1Department of Nephrology, School of Medicine, Faculty of Medicine, Saitama Medical University, Saitama, Japan
2Community Health Science Center, Saitama Medical University, Saitama, Japan
Address correspondence to Hiromichi Suzuki, MD, PhD, Department of Nephrology, School of Medicine, Faculty of Medicine, Saitama Medical University, 38 Morohongo Moroyama, Iruma, Saitama, 350-0495 Japan
ABSTRACT