[Incremental doses of diltiazem in patients with coronary artery disease in end-stage renal failure maintained on hemodialysis: which is the optimal dose?].
End-stage renal disease patients on maintenance hemodialysis suffering from coronary artery disease probably receive too low doses of calcium-antagonists, because the attempt to avoid adverse effects prevails the well-documented antianginal activity of the drug. The aim of our study was to assess the safety and efficacy of incremental doses of diltiazem in treating angina pectoris in hemodialyzed patients with coronary artery disease, to identify the optimal dose. Ninety-four chronic hemodialyzed patients (59 males and 35 females; mean age 55.2 +/- 3.3 years; on periodic dialysis for 80.3 +/- 25.6 months) with coronary artery disease and more than 5 min of transient myocardial ischemia during 48 hours of Holter monitoring were included in the study. A double-blind, randomized, placebo-controlled trial design was used. Incremental doses of diltiazem (from 120 to 240 mg/day) were administered in 4 months. At doses of 120 and 180 mg/day it was observed a statistically significant reduction in the number and duration of total and symptomatic ischemic episodes in 48 hours, compared with baseline (p < 0.001). Instead, the number and the duration of silent ischemic episodes did not significantly change (NS). The efficacy on silent myocardial ischemia was obtained only with the dosage of 240 mg/day (p < 0.001). If this dosage was obtained with a sustained-release formulation (120 mg twice a day), the efficacy was similar to the administration of 4 tablets/day of 60 mg, but the tolerability was better, especially during dialysis. The circadian variations of transient ischemic episodes showed two peaks in the 24 hours, one from 6.00 to 9.00 a.m. and another from 4.00 to 8.00 p.m., just during the dialysis. Both peaks were reduced only with 240 mg/day. In conclusion, this study demonstrates that sustained-release diltiazem (120 mg twice a day) is greatly useful in patients with coronary artery disease on maintenance dialysis because it reduces the frequency of silent ischemic episodes, has a good tolerability, and modifies the circadian pattern of ischemic episodes, reducing both peaks during the day.
Cice
G
G
Cattedra di Cardiologia, Istituto Medico-Chirurgico di Cardiologia, Seconda Università degli Studi, Napoli.
Ferrara
L
L
Tagliamonte
E
E
Di Benedetto
A
A
Iacono
A
A
D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D003327:Coronary Disease / Q000150:complications* / Q000188:drug therapy*; D004110:Diltiazem / Q000008:administration & dosage*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006334:Heart Function Tests; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis