Key result
Isosorbide dinitrate and hydralazine increase adverse events ~81% in hemodialysis despite reducing recurrent intradialytic hypotension.
Why the study?
The safety and tolerability of combination isosorbide dinitrate and hydralazine in individuals requiring maintenance hemodialysis was unknown.
Does combination isosorbide dinitrate and hydralazine increase adverse events in individuals requiring maintenance hemodialysis?
RCT (n=17)
double-blind
randomized
No
Does combination isosorbide dinitrate and hydralazine increase adverse events in individuals requiring maintenance hemodialysis?
Absolute Event Rate: 11.4% vs 6.31%
In a pilot trial of maintenance hemodialysis patients, combination isosorbide dinitrate and hydralazine was tolerated but associated with more frequent adverse events, particularly nausea, while reducing intradialytic hypotension.
Tolerable in HD patients despite more GI events; leaves open larger efficacy and safety trials before practice consideration.
Background Combination therapy with isosorbide dinitrate (ISD) and hydralazine (HY) reduces heart failure mortality. The safety and tolerability in individuals requiring maintenance hemodialysis (HD) is unknown. Methods Single-center, randomized, placebo-controlled, double-blind pilot trial to explore safety and tolerability of ISD/HY in maintenance HD. Participants were randomized to placebo or combination ISD/HY. Dose was escalated over 3 weeks from ISD 10 mg/HY 10 mg to ISD 40 mg/HY 75 mg three times per day with the maximum tolerated dose maintained for the subsequent 21 weeks. Primary endpoints included adverse events, adverse events precluding further treatment with study medication, serious hypotension ( i.e ., requiring hospitalization or emergency room visit), and recurrent intra-dialytic hypotension. Efficacy signals included change in mitral annular E’ velocity by tissue Doppler echocardiography and change in left ventricular coronary flow reserve on positron emission tomography. Results A total of 17 individuals were randomized to ISD/HY ( N =7) or placebo ( N =10). All participants assigned to ISD/HY completed dose escalation to 40/75 mg, but dose reductions were required in two participants. No participants discontinued therapy. There were no serious hypotension events. Recurrent intradialytic hypotension was less frequent with ISD/HY (0.47 events/patient-year) than placebo (1.83 events/patient-year, P =0.04). In contrast, nausea (ISD/HY, 1.90 events/patient-year; placebo, 0.50 events/patient-year, P =0.03) was significantly more frequent, and headache and diarrhea were numerically but not significantly more frequent with ISD/HY. Adverse events were more frequent with ISD/HY (11.4 events/patient-year) than placebo (6.31 events/patient-year). We did not detect between-group differences in the change in E’ ( P =0.34); ISD/HY showed a mean increase of 0.6 cm/s (SD 1.1), and placebo showed a mean decrease of 0.04 cm/s (SD 0.9). Changes in coronary flow reserve were minimal, −0.3 (0.2) with ISD/HY and −0.03 (0.5) in the placebo group, P =0.19. Conclusions ISD/HY appears to be well tolerated in patients being treated with maintenance HD, but headache and gastrointestinal side effects occur more frequently with ISD/HY compared with placebo.
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Charytan et al. (2020) conducted an RCT in Dialysis-dependent ESRD (n=17). Combination isosorbide dinitrate (ISD) and hydralazine (HY) vs. Placebo was evaluated on Adverse events. Combination isosorbide dinitrate and hydralazine in hemodialysis patients increased adverse events (11.4 vs 6.31 events/patient-year) but reduced recurrent intradialytic hypotension (P=0.04).
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