NEW YORK – Patients treated with carvedilol not only had a reduced frequency of intradialytic hypertension, but also showed improvements in endothelial cell function, in a small study.
After 8 weeks of treatment with carvedilol, mean systolic postdialysis blood pressure dropped from 159 mm Hg at baseline to 142 mm Hg, reported Dr. Julia Inrig of the University of Texas Southwestern Medical Center in Dallas.
We are “very interested in this phenomenon of intradialytic hypertension,” she said at the meeting. When most patients come for dialysis, there is a gradual reduction in their systolic blood pressure. “However, up to 20% of patients have this gradual increase in their systolic blood pressure during their dialysis. So they leave their dialysis session much more hypertensive than when they showed up, despite similar amounts of fluid removed.”
In addition, “we've identified that this is an important prognostic indicator.” In a cohort of 450 dialysis patients, those with increased BP during dialysis were nearly twice as likely to be hospitalized or die by 6 months (Kidney Int. 2007;71:454-61).
The researchers in the Mechanisms and Treatment of Intradialytic Hypertension (MATCH) pilot study prospectively enrolled 25 hemodialysis patients with intradialytic hypertension into an open-label intervention study. Once patients were accepted into the study, they underwent baseline testing, including 44-hour ambulatory blood pressure, lipids, albumin, sodium, and C-reactive protein, as well as postdialysis endothelin-1, asymmetric dimethylarginine, endothelial progenitor cells, pulse-wave velocity, and brachial artery flow. In 8 weeks, the baseline lab work was repeated.
Patients were started on carvedilol 6.25 mg twice daily, and eventually titrated to 50 mg twice daily. “Our goal was to reach a delta [systolic] blood pressure less than zero with regard to their postdialysis blood pressure no longer increasing,” said Dr. Inrig. However, she and her colleagues were also targeting a postdialysis systolic BP of less than 130 mm Hg as an alternative goal.
The average patient age was 54 years, and the group was 80% male. Roughly two-thirds of the population was Hispanic (64%), and more than a third was black (36%). Almost all (88%) had diabetes, and 32% had cardiovascular disease. Many were on ACE inhibitors or angiotensin II receptor blockers (64%), beta-blockers (68%), or calcium channel blockers (60%) at baseline.
Mean predialysis BP was roughly the same regardless of carvedilol treatment (144 mm Hg vs. 146 mm Hg). The frequency of intradialytic hypertension declined from 77% of hemodialysis sessions at baseline to 28% by the study's end, a significant difference.
Carvedilol treatment showed a trend toward improvement of brachial artery flow–mediated dilation. However there was no change in C-reactive protein or pulse-wave velocity.
“With regard to safety, patients tolerated carvedilol fairly well,” said Dr. Inrig. There was a low incidence of side effects.
Dr. Inrig has received an investigator-initiated research grant from Genzyme, and has participated in industry-sponsored research for Keryx Biopharmaceuticals.