An estimated 26 million adults in the United States are affected by chronic kidney disease (CKD); approximately 40% of which also suffer from cardiovascular disease (CVD).1,2 Evidence clearly shows that beta-adrenergic receptor antagonists (“beta-blockers”) have a mortality benefit in patients with heart failure and after an acute myocardial infarction.3 However, patients with CKD are excluded in the majority of the randomized controlled trials that provided such evidence.4 A multi-national meta-analysis conducted by Badve et al. explored the available evidence to determine the risks and benefits of using beta-blockers in patients with CKD.3
Trials for the systematic review and meta-analysis were selected using appropriate electronic searches through Medline via Ovid, EMbase, and the CENTRAL database. Other literature searched included review articles, other systematic reviews, treatment guidelines, textbook chapters, conference proceedings, and online trial registries. Randomized controlled trials were eligible for inclusion if they included participants with CKD stages 3 to 5 (eGFR < 60 ml/min/1.73 m2), including dialysis patients, who were randomized to an oral beta-blocker therapy. Trials were excluded if they were non-randomized, followed patients for a duration of less than 3 months, included data on patients with no or mild (stage 1 or 2) CKD, and used beta-blockers in both treatment arms. A total of 6,949 patients from 8 different trials (heart failure and non-heart failure trials) were included in the systematic review. However, only 6 randomized placebo-controlled trials (5,972 patients) in patients with heart failure and chronic kidney disease were analyzed in the meta-analysis with the primary outcome of all-cause mortality. Other reported clinical outcomes included cardiovascular mortality, sudden death, and all-cause hospitalization. The trials that included patients with heart failure were separated from the non-heart failure trials because of the considerable differences in cardiovascular morbidity, comparator, and duration of follow-up. In each of the trials, all patients received oral beta-blocking therapy compared to either placebo, another cardiovascular agent of a different class, or no treatment. Appropriate doses of the following beta-blockers were used: carvedilol, bisoprolol, metoprolol XL/CR, nebivolol, and acebutolol. Nebivolol and acebutolol were used in the non-heart failure trials.
In patients with moderate CKD and heart failure, beta-blocking therapy exhibited a 28% relative reduction in all-cause mortality (95% CI -36% to -20%; p<0.001) and a 34% relative reduction in cardiovascular mortality as compared to placebo (95% CI -51% to -11%; p=0.006). The investigators found no significant difference between the discontinuation rates of patients receiving beta-blockers versus other treatments. However, 4 trials reported there was a statistically significant increase (p<0.001) in the amount of bradycardia and hypotension in patients on beta-blocking therapy. A meta-analysis of randomized controlled trials is the highest level of evidence available. However, in this meta-analysis only a small number of heart failure studies were included, and the majority of the data were from post hoc analyses. Most of the patients included only had moderate decreases in GFR (between 45 and 60 ml/min/1.73 m2). Therefore, the evidence presented in this meta-analysis does not apply as strongly to patients with a GFR less than 45 ml/min/1.73 m2. Due to the lack of data in these patients, health professionals will have to continue extrapolating data from the general population to treat patients with low GFRs or end-stage renal disease. There remains a great deal to be discovered on the possible risks and benefits of beta-blockers in patients without heart failure, specifically those who have progressed to the later stages of CKD.
1. Coresh J, Selvin E, Stevens LA, et al. Prevalence of chronic kidney disease in the United States. JAMA 2007;298:2038-2047.
2. National Kidney Foundation KDOOQI Guidelines. KDOQI Clinical Practice Guidelines ...