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when compared with those treated with monotherapy. Larger studies are required to
determine whether this therapeutic combination can improve cardiovascular out-
comes in HD patients.
A multicenter RCT [ 64 ] investigated the antihypertensive effect of the DRI
aliskiren in comparison with the CCB amlodipine in 83 HD patients with difficult-
to- treat or resistant hypertension. The baseline medications were dual therapy in
60% and therapy with ≥3 drugs in 40% of cases. Most patients (77%) were on
ARBs or ACEIs. A significant decrease in BP was found only in the amlodipine
group, but not in the aliskiren group.
Mineralocorticoid Receptor Antagonists
The use of these agents in HD patients has not been thoroughly investigated, but it
may be limited because of fear of the risk of hyperkalemia, particularly in anuric
patients [ 47 ]. In two small open-label studies of low-dose (25 mg) spironolactone
[ 65 , 66 ], there was no significant increase in serum potassium with thrice weekly
administration, but 7% of patients with daily dosage of the drug were withdrawn
because of severe hyperkalemia. In a larger study of spironolactone 25 mg/day in 61
oligoanuric HD patients, potassium levels increased overall (from 4.6 to 5.0 mEq/l)
with treatment; however, no patients had a potassium >6.8 mEq/l or required ion
exchange resin therapy [ 67 ]. While these studies suggest that MR antagonists may
be relatively safe, further research is required prior to their use in dialysis patients.
Beta-Blockers
BBs are important antihypertensive agents for HD patients and are particularly indi-
cated in those with coronary artery disease and heart failure [ 47 ]. In a secondary
analysis of 11,142 prevalent HD patients from the United States Renal Database
Systems (USRDS) Wave 3 and 4 Study, Foley et al. [ 68 ] found that the use of BBs
was associated with a 16% lower adjusted risk of death. Two small RCTs by Cice
et al. [ 69 , 70 ] showed that carvedilol therapy, as compared to placebo, improved
cardiac structure and function, as well as survival, in HD patients with heart
failure.
Atenolol and metoprolol are dialyzable and require supplementation after dialy-
sis, while combined α- and β-blockers (e.g., carvedilol) are not significantly cleared
by HD. Metoprolol is mainly metabolized by the liver and therefore does not require
dose adjustment, while atenolol is excreted mainly by the kidneys, and, thus, its half-
life is prolonged in HD patients. Carvedilol is a nonselective inhibitor of β-adrenergic
receptors and, theoretically, may increase the risk of hyperkalemia [ 47 ].
L. Segall