Antihypertensive treatment with a vasodilating beta-blocker, carvedilol, in chronic hemodialysis patients

Abstract

Carvedilol is an antihypertensive agent which displays unselective beta-blocking, alpha 1-blocking and antioxidant properties. It is primarily metabolized by the liver and excreted via the biliary system. The compound is highly lipophilic and strongly bound to plasma proteins. Consequently, there is no elimination during hemodialysis. The efficacy, safety, and pharmacokinetic profile of carvedilol titrated to effect were investigated in an open clinical trial in 15 long-term hemodialysis patients with arterial hypertension over a period of 12 weeks. The drug was administered only on days without dialysis. After a wash-out phase of one week, carvedilol was started in a dose of 12.5 mg per day. All 15 patients were titrated according to the antihypertensive effect to a daily dose of 25 mg of carvedilol. Carvedilol was effective in lowering blood pressure in hemodialysis patients (RR systolic: 170 +/- 11 vs. 144 +/- 9 mmHg; RR diastolic: 98 +/- 10 vs. 85 +/- 10 mmHg). The pharmacokinetic parameters of carvedilol and its active metabolite M2, assessed in 12 of the 15 patients, were not influenced by the lack of renal function or intermittend haemodialysis. In particular, there was no accumulation of carvedilol or its metabolite M2. In terms of side effects, three patients had to be withdrawn from the trial, because of hypoglycemia (n = 1), insufficient blood pressure control (n = 1) and prolonged hypotension (n = 1). Taken together, these results indicate that carvedilol is a safe and efficacious antihypertensive agent which can be used in patients maintained by maintenance dialysis treatment.